**Workshop Report**

**Basic Research Needs for Countering Terrorism**

Sponsored by

Office of Basic Energy Sciences

Office of Science

U.S. Department of Energy

Terry Michalske (SNL/NM), Workshop Chair and Volume Editor

Norman Edelstein (LBNL), Radiological/Nuclear Threats Chair

Michael Sigman (ORNL), Chemical Threats Chair

Jill Trewhella (LANL), Biological Threats Chair

Prepared by:

Sandia National Laboratories

P.O. Box 5800

Albuquerque, New Mexico 87185-1413

**Abstract**

This report documents the results of the Office of Basic Energy Sciences
(BES) Workshop on Basic Research Needs to Counter Terrorism. This
two-day Workshop, held in Gaithersburg, MD, on February 28 and March 1,
2002, brought together BES research participants and experts familiar
with counter-terrorism technologies, strategies, and policies. The
purpose of the workshop was to: (1) identify direct connections between
technology needs for countering terrorism and the critical, underlying
science issues that will impact our ability to address those needs and
(2) recommend investment strategies that will increase the impact of
basic research on our nation's efforts to counter terrorism.

**Contents**

[**Executive Summary 5**](#executive-summary)

[1 Introduction 9](#introduction)

[1.1 Context for Scientific and Technological Applications for
Countering Terrorism
11](#context-for-scientific-and-technological-applications-for-countering-terrorism)

[1.2 Opportunities for Basic Research
11](#opportunities-for-basic-research)

[1.3 Challenges to the Basic Research Community
12](#challenges-to-the-basic-research-community)

[2 Radiological/Nuclear Threats 15](#radiologicalnuclear-threats)

[2.1 Terrorism Threats and Technology Needs
15](#terrorism-threats-and-technology-needs)

[2.1.1 Detection 16](#detection)

[2.1.2 Preparedness 18](#preparedness)

[2.1.3 Prevention 19](#prevention)

[2.1.4 Protection/Response and Recovery
20](#protectionresponse-and-recovery)

[2.2 BES Research Accomplishments and Implications for Counter Terrorism
21](#bes-research-accomplishments-and-implications-for-counter-terrorism)

[2.2.1 Heavy Element Chemistry 21](#heavy-element-chemistry)

[2.2.2 Separations and Analysis 24](#separations-and-analysis)

[2.2.3 Radiation Chemistry 28](#radiation-chemistry)

[2.2.4 Experimental Condensed Matter Physics
28](#experimental-condensed-matter-physics)

[2.2.5 Mechanical Behavior of Materials and Radiation Effects
29](#mechanical-behavior-of-materials-and-radiation-effects)

[2.2.6 Synchrotron and Neutron User Facilities
29](#synchrotron-and-neutron-user-facilities)

[2.2.7 Geosciences 29](#geosciences)

[2.3 Scientific Issues and Research Opportunities
32](#scientific-issues-and-research-opportunities)

[2.3.1 Detection 32](#detection-1)

[2.3.2 Preparedness 37](#preparedness-1)

[2.3.3 Prevention 39](#prevention-1)

[2.3.4 Protection/Response and Recovery
41](#protectionresponse-and-recovery-1)

[2.4 Research Needs 46](#research-needs)

[2.4.1 Scientific Issues 46](#scientific-issues)

[2.4.1 Research Environment and Infrastructure
48](#research-environment-and-infrastructure)

[2.4.3 Relationships with Other Programs
50](#relationships-with-other-programs)

[2.4.4 Dual-Use Opportunities 51](#dual-use-opportunities)

[3 Chemical Threats 53](#chemical-threats)

[3.1 Terrorism Threats and Technology Needs
53](#terrorism-threats-and-technology-needs-1)

[3.1.1 Chemical Warfare Agents 53](#chemical-warfare-agents)

[3.1.2 TIMs 55](#tims)

[3.1.3 Explosives 56](#explosives)

[3.2 BES Research Accomplishments and Implications for Countering
Terrorism
58](#bes-research-accomplishments-and-implications-for-countering-terrorism)

[3.2.1 Detection 58](#detection-5)

[3.2.2 Preparedness 66](#preparedness-2)

[3.2.3 Prevention 66](#prevention-2)

[3.2.4 Protection 67](#protection)

[3.2.5 Response and Recovery 68](#response-and-recovery)

[3.3 Scientific Issues and Research Opportunities
69](#scientific-issues-and-research-opportunities-1)

[3.3.1 Detection 69](#detection-6)

[3.3.2 Prevention 78](#prevention-3)

[3.3.3 Protection, Response, and Recovery
79](#protection-response-and-recovery)

[3.3.4 Preparedness 84](#preparedness-3)

[3.4 Research Needs 85](#research-needs-1)

[3.4.1 Scientific Issues 85](#scientific-issues-1)

[3.4.2 Research Environment and Infrastructure
86](#research-environment-and-infrastructure-1)

[3.4.3 Relationships with Other Programs
87](#relationships-with-other-programs-1)

[3.4.4 Dual-Use Opportunities 87](#dual-use-opportunities-1)

[4 Biological Threats 89](#biological-threats)

[4.1 Terrorism Threats and Technology Needs
89](#terrorism-threats-and-technology-needs-2)

[4.2 BES Research Accomplishments and Implications
93](#bes-research-accomplishments-and-implications)

[4.2.1 Nanophase Materials 93](#nanophase-materials)

[4.2.2 Interfaces 98](#interfaces)

[4.2.3 Integrated Systems 98](#integrated-systems)

[4.2.4 Atomic and Molecular Spectroscopy
98](#atomic-and-molecular-spectroscopy-1)

[4.3 Scientific Issues and Opportunities
102](#scientific-issues-and-opportunities)

[4.3.1 Detection and Identification 102](#detection-and-identification)

[4.4 Medical Diagnostics 115](#medical-diagnostics)

[4.4.1 Protection 121](#protection-1)

[4.4.2 Decontamination and Remediation
124](#decontamination-and-remediation)

[4.5 Research Needs 128](#research-needs-2)

[4.5.1 Scientific Issues 128](#scientific-issues-2)

[4.5.2 Research Environment and Infrastructure Requirements
130](#research-environment-and-infrastructure-requirements)

[4.5.3 Relationships with Other Programs
130](#relationships-with-other-programs-2)

[4.5.4 Dual-Use Opportunities 132](#dual-use-opportunities-2)

[5 Workshop Conclusions and Recommendations
135](#workshop-conclusions-and-recommendations)

[5.1 Cross-Cutting Research 136](#cross-cutting-research)

[5.2 Research Environments and Infrastructures
137](#research-environments-and-infrastructures)

[5.3 Relationships with Other Programs
139](#relationships-with-other-programs-3)

[5.4 Dual-Use Opportunities 139](#dual-use-opportunities-3)

[Appendix I - CT Roster 141](#appendix-i---ct-roster)

# Executive Summary {#executive-summary .unnumbered}

This report documents the results of the Department of Energy, Office of
Basic Energy Sciences (BES) Workshop on Basic Research Needs to Counter
Terrorism. This two-day Workshop, held in Gaithersburg, MD, on February
28 and March 1, 2002, brought together BES research participants and
experts familiar with counter-terrorism technologies, strategies, and
policies. The purpose of the workshop was to: (1) identify direct
connections between technology needs for countering terrorism and the
critical, underlying science issues that will impact our ability to
address those needs and (2) recommend investment strategies that will
increase the impact of basic research on our nation's efforts to counter
terrorism.

The workshop focused on science and technology challenges associated
with our nation's need to detect, prevent, protect against, and respond
to terrorist attacks involving Radiological and Nuclear, Chemical, and
Biological threats. While the organizers and participants of this
workshop recognize that the threat of terrorism is extremely broad,
including food and water safety as well as protection of our public
infrastructure, we necessarily limited the scope of our discussions to
the principal weapons of mass destruction.

In order to set the stage for the discussions of critical science and
technology challenges, the workshop began with keynote and plenary
lectures that provided a realistic context for understanding the broad
challenges of countering terrorism. The plenary speakers emphasized the
socio-political complexity of terrorism problems, reinforced the need
for basic research in addressing these problems, and provided critical
advice on how basic research can best contribute to our nation's needs.
Their advice highlighted the need to:

-   [Invest Strategically]{.underline} -- Focus on ***Cross-Cutting
    Research*** that has the potential to have an impact on a broad set
    of technology needs, thereby providing the greatest return on the
    research investment.

-   [Build Team Efforts]{.underline} -- Countering terrorism will
    require broad, collaborative teams. The research community should
    focus on: (1) ***Research Environments and Infrastructures*** that
    encourage and enable cross-disciplinary science and technology teams
    to explore and integrate new scientific discoveries and (2)
    Exploring ***Relationships with Other Programs*** that will
    strengthen connections between new scientific advances and those
    groups responsible for technology development and implementation.

-   [Consider Dual Use]{.underline} -- Identify areas of research that
    present significant ***Dual-Use Opportunities*** for application to
    countering terrorism and other complementary technology needs.

The during the workshop, participants identified several critical
technology needs and the underlying science challenges that, if met, can
help to reduce the threat of terrorist attacks in the United States.
Some of the key technology needs and limitations that were identified
include:

*Detection* -- Nonintrusive, stand-off, and imaging detection systems;
sampling from complex backgrounds and environments; inexpensive and
field-deployable sensor systems; highly selective and ultra-sensitive
detectors; early warning triggers for continuous monitoring

*Prevention* -- Methods and materials to control, track, and reduce the
availability of hazardous materials; techniques to rapidly characterize
and attribute the source of terrorist threats

*Protection* -- Personal protective equipment; light-weight barrier
materials and fabrics; filtration systems; explosive containment
structures; methods to protect people, animals, crops, and public spaces

*Response* -- Coupled models and measurements that can predict fate and
transport of toxic materials including pre-event background data;
pre-symptomatic and point of care medical diagnostics; methods to
immobilize and neutralize hazardous materials including self-cleaning
and self-decontaminating surfaces

The workshop discussions of these technology needs and the underlying
science challenges are fully documented in the major sections of this
report. The results of these discussions, combined with the broad
perspective and advice from our plenary speakers, were used to develop a
set of high-level workshop recommendations. The following
recommendations are offered to help guide our nation's basic research
investments in order to maximize our ability to reduce the threat of
terrorism.

-   We recommend continuing or increasing funding for a selected set of
    research directions that are identified in the Workshop Summary and
    Recommendations (Section 5) of this report. These areas of research
    underpin many of the technologies that have high probability to
    impact our nation's ability to counter terrorism.

-   New programs should be supported to stimulate the formation of, and
    provide needed resources for, cross-disciplinary and
    multi-institutional teams of scientists and technologists that are
    needed to address these critical problems. An important component of
    this strategy is investment in DOE national laboratories and user
    facilities because they can provide an ideal environment to carry
    out this highly collaborative work.

-   Governmental organizations and agencies should explore their
    complementary goals and capabilities and, where appropriate, work to
    develop agreements that facilitate the formation of
    multi-organizational teams and the sharing of research and
    technology capabilities that will improve our nation's ability to
    counter the threat of terrorism.

-   Increased emphasis should be placed on identifying dual-use
    applications for key counter-terrorism technologies. Efforts should
    be focused on building partnerships between government, university,
    and industry to capitalize on these opportunities.

In summary, this workshop made significant progress in identifying the
basic research needs and in outlining a strategy to enhance the research
community's ability to impact our nation's counter-terrorism needs. We
wish to acknowledge the enthusiasm and hard work of all the workshop
participants. Their extraordinary contributions were key to the success
of this workshop, and their dedication to this endeavor provides strong
evidence that the basic research community is firmly committed to
supporting our nation's goal of reducing the threat of terrorism in the
United States.

# Introduction

This report documents the presentations, discussions, and
recommendations from the Department of Energy / Office of Basic Energy
Sciences (BES) Workshop on Basic Research Needs to Counter Terrorism.
The workshop, which was held on February 28 and March 1, 2002, in
Gaithersburg, Maryland, identified the critical science issues and
opportunities in research areas supported by BES that will be important
to our nation\'s ability to detect, prevent, protect against, and
respond to terrorist threats in the United States.

While terrorism is not new to the international community, events in
recent years such as the 1993 bombing of the World Trade Center and the
attack on the Alfred P. Murrah Federal Building in Oklahoma City in 1995
have shown that assets on United States soil have also become targets
for terrorist activities. Most recently, the September 11 suicide
attacks resulted in the deaths of more than 3,000 civilians. These
devastating events have focused the attention of the entire world and
caused the United States to launch a War on Terrorism. A major response
to these terrorist events has been the formation of the Office of
Homeland Security to develop, coordinate, and implement a comprehensive
national strategy to detect, prevent, protect against, and respond to
terrorist attacks within the United States.

This nation's strengths in basic science research are expected to play
an important role in the initiative to counter the threat of terrorism.
In his speech before the American Association for the Advancement of
Science in December 2001, Dr. John H. Marburger III, Director of the
White House Office of Science and Technology Policy, stated, "Science
and engineering have critical roles to play in the war on terrorism." He
went on to indicate, "We need improved tools with which to prevent,
detect, protect, and treat victims of chemical biological, radiological,
nuclear, and conventional terrorist attacks. Additionally, we will need
new and improved tools to recover facilities from those same types of
attacks, should they ever occur."

As a leading supporter of basic science research, the Office of Basic
Energy Sciences convened a workshop to understand better how fields of
research that it supports can meet our nation's needs to counter
terrorism. This workshop involved participants from the BES research
community (including scientists from national laboratories and
universities), experts in the technologies, strategies, and policies
used to counter terrorism, and representatives from several other
governmental agencies and organizations. Appendix I gives a list of
participants in the intensive two-day workshop.

There are many examples where basic science research and resulting
technology can impact the ability to detect, prevent, protect against,
and respond to terrorism. For example, sensors, detectors, chem lab on a
chip, and atomic and molecular spectroscopy could all be important to
the *Detection* of terrorism. *Prevention* of terrorist acts could be
enhanced through improved methods for controlling and tracking
radiological materials and the development of new manufacturing methods
that minimize the creation of hazardous industrial chemicals. Likewise,
*Protection* against terrorism could be increased through improved
filters and membranes and the development of new protective fabrics,
while improvements in our ability to *Respond* to a terrorist event
could be made by developing methods to immobilize and neutralize
hazardous materials.

*The goal of this workshop was to identify direct connections between
technology needs for countering terrorism and the critical, underlying
science issues that will impact our ability to address those needs.*

To set the stage for the discussions of critical science and technology
challenges, the workshop began with keynote and plenary lectures that
provided a realistic context for understanding the broad challenges of
countering terrorism:

-   Dr. Jay Davis, National Security Fellow at the Center for Global
    Security Research at Lawrence Livermore National Laboratory (LLNL),
    provided the keynote lecture entitled "The Role of Science and
    Technology in Countering Terrorism." Dr. Davis spent three years
    prior to returning to LLNL as founding director of the Defense
    Threat Reduction Agency of the Department of Defense. His
    presentation stressed the overall socio-political complexity of the
    terrorism problem.

-   Dr. Micheal R. Anastasio, Deputy Director for Strategic Operations
    at LLNL, lectured on "Counter Terrorism and Long-Range R&D Needs."
    Dr. Anastasio serves on the National Academy of Sciences Sub-Panel
    on Radiological and Nuclear Threats and focused on the principal
    threats associated with radiological and nuclear materials.

-   Professor Micheal J. Sailor from the University of California at San
    Diego focused on "Basic Research Needs to Counter Chemical Threats."
    Prof. Sailor stressed the need for science and technology
    integration to allow new scientific breakthroughs to impact the
    practical tasks of fighting terrorism.

-   The final plenary lecture addressed the biological threat and was
    presented by Dr. David Franz (Colonel, U.S. Army Retired), Vice
    President, Chemical and Biological Defense Division of Southern
    Research Institute. Dr. Franz has served as both Deputy Commander
    and then Commander of the U.S. Army Medical Research Institute of
    Infectious Diseases (USARMID).

This panel of experts shared some very important perspectives with the
workshop participants concerning the nature of terrorist threats, the
complex processes involved in countering these threats, and the
important role that basic science can play. Although we could never
capture the full impact of these presentations in our written report,
the following sections summarize some of the key points associated with
basic science's role in countering of terrorism.

## Context for Scientific and Technological Applications for Countering Terrorism 

To enhance the nation's ability to counter terrorism, one must first
recognize that terrorism is an extremely complex socio-political problem
and that there are simply no "Silver Bullets" to easily solve the
problem.

-   Scientific breakthroughs or new technologies alone will not end
    terrorism. Any solution must be compatible with existing doctrine,
    operations, and training. In other words, to be useful, science and
    technology must be considered as part of an overall system, and the
    technological piece of that system must be simple and easy to use.

-   It is important to note that no one customer exists for new science
    and technology applications for countering terrorism. In fact, there
    are many customers, none of which has sole responsibility for
    countering terrorism in the U.S.

-   Finally, the ultimate customers are not familiar with science and
    technology and are unlikely to understand or appreciate the needs or
    capabilities of the basic research community, but that does not mean
    that they will not ultimately benefit from research efforts.

## Opportunities for Basic Research

While the context for understanding terrorism is very complex (and
somewhat daunting), there are many important contributions that science
and technology can make:

-   The strength of basic research is in new knowledge and the
    associated cost effectiveness. Terrorism presents tough problems,
    and new approaches can be extremely valuable.

-   Basic research can provide assistance across all categories of
    homeland security; however, the special relationship between
    *detection* and *response* (forensics and attribution) presents some
    of the more significant opportunities. Our nation's terrorism
    policies stress retribution and rapid identification of those
    responsible.

-   The ability to couple physical measurements with modeling tools is
    very important. Too often, those responding to terrorist acts either
    have measurements but no models to help in understanding their
    significance, or they have models with no actual data to guide their
    application. In addition, tools to help interpret sparse data sets
    or to analyze large volumes of data will also be extremely useful.

-   Dual-use is an extremely important concept and can contribute to the
    "critical mass" of interest needed to support science and technology
    investments. A good example might be a scientific goal that
    contributes to the development of a biohazard detector, but at the
    same time, it has relevance to human health diagnostics.

## Challenges to the Basic Research Community

The challenges that our plenary speakers addressed were not those
associated with the science itself but with the scientist's and
technologist's interface with the overall efforts to counter terrorism.

-   Scientists and technologists must be honest and straightforward
    about what is possible and what is not. Those responsible for
    countering terrorism are looking for solutions, not hype.

-   The basic research community must be prepared to work with a team
    that they will probably not lead. Scientists will set the scientific
    directions but not the overall approach and strategy for countering
    terrorism. Thus, scientists and technologists will need to
    understand enough about the overall approaches to countering
    terrorism that they can understand the true value of their work to
    that broader integrated effort.

-   The focus on integration, both at a systems level and at a
    technology level, must be constantly addressed.

With this background and perspective in place, the workshop participants
divided into smaller groups to discuss specific technology needs and
critical scientific issues. The following sections summarize the
workshop discussions and address the Radiological and Nuclear, Chemical,
and Biological threat areas. Each section separately addresses (1) the
technology needs posed by terrorist threats in that area, (2) specific
examples of how basic research supported by the BES Materials and
Chemical Sciences programs already plays an important role in the effort
to counter terrorism,[^1] (3) the fundamental scientific issues and
challenges that promise to impact the ability to counter terrorism, and
(4) future research needs, including new science thrusts as well as new
facilities and infrastructure development.

The participants in this workshop fully recognize that the threat of
terrorism extends beyond the topics addressed in this workshop. Of
particular interest to the Department of Energy is the potential
vulnerability of our nation's critical infrastructure for energy,
information, and transportation. The Basic Energy Sciences Advisory
Committee is planning a separate comprehensive workshop structured
around energy reserves, production, and consumption with break-out
sessions for specific energy sources and consumption sectors.

# Radiological/Nuclear Threats

## Terrorism Threats and Technology Needs

The nuclear threats facing the U.S. are constantly evolving and have
grown more complex since the end of the Cold War. However, the events of
this past year have proved the necessity to reevaluate these threats on
a scale never before considered.

In the past, potential adversary states were easily identified, and
nuclear weapons program development was monitored through treaties,
intelligence agencies, nuclear reactor monitoring, and scientific
advancements. With the dissolution of the Soviet Union, the possibility
of diversion of complete weapon systems or nuclear material to rogue
nations and terrorist organizations has increased. In addition, new
nuclear powers (e.g., Pakistan and India) have further complicated
global proliferation issues. While the operability of nuclear weapons
has always been important to national security, their role has been more
as a strategic deterrent rather than as an offensive/defensive weapon.
In the current climate, complex and highly organized domestic and
state-sponsored foreign terrorist units have multiple mechanisms at
their disposal to engage in nuclear threats. In addition, the potential
threat scenarios have now been expanded to consider the use of all
radiological materials as potential "weapons," introducing the need to
monitor, track, and respond to a greatly broadened suite of
materials.^1^

The most potentially catastrophic terrorist threat involving radioactive
materials is the possibility of a self-sustained fission chain reaction
detonated in an urban area. This scenario is credible and is taken very
seriously by the federal authorities. Such an event could result in a
significant number of deaths and massive devastation. The resulting
fallout, containing highly radioactive fission and activation products,
would contaminate many square miles. Such a device need only contain
several kilograms to a few tens of kilograms of a fissile isotope, could
be transported in a small truck, and would be difficult to detect
because of the relatively small amount of external radiation that it
would produce, especially if shielded, before detonation.

Prevention of such a devastating terrorist attack requires that
terrorists do not obtain the essential ingredient for building an atomic
bomb, namely, fissile actinide isotopes such as U-235 or Pu-239. If they
have obtained such isotopes, the fissile material must be detected
before introduction into the U.S., or during transport and before
assembly into a functional device. Other credible threat scenarios
include the use of radiological materials as potential weapons. A
noninclusive list of potential threats includes the use of so-called
"alternate nuclear materials" or the generation of "dirty" bombs, which
use a combination of conventional explosives and nuclear material.
Radionuclide release may occur from the sabotage of nuclear facilities
or repositories, from raids/attacks on nuclear materials in transport,
or from hospitals where radionuclides are used for diagnostics and
therapy.

To realize how work supported by the Office of Basic Energy Science can
impact homeland defense and counter terrorism, an understanding of the
threats and the mechanism of a nuclear-based terrorist attack is
required. The threats discussed above have common features. The three
basic objectives for a terrorist are to obtain radiological or nuclear
materials, to develop or utilize known technology for "weaponization,"
and to deploy the weapon/material in a desirable area. Within each of
these objectives are inherent weaknesses that a counter-terrorism effort
can exploit.

### Detection

The primary goal of any counter-terrorism effort is to prevent an attack
as early in the development stages as possible. Many current approaches
employed to prevent a nuclear/radiological attack rely upon detection of
materials. Access to nuclear or radiological materials as well as weapon
production capabilities and facilities has been considered of primary
importance.^2^

Many technologies have been proposed for monitoring production, from
radiation detection methods employed in on-site inspection governed by
treaties to stand-off detection of chemical effluents resulting from the
processing of nuclear materials.^3^ Several factors complicate the
application of such methods, however. First, the list of fissionable
isotopes that merit monitoring has been expanded to include potential
"alternate nuclear materials," including Np-237 and certain isotopes of
Am. Furthermore, the possible use of a "dirty" nuclear device, or a
combination of a conventional and a nuclear explosive device, brings any
radioactive material into the realm of a potential threat.

The need to detect both traditional and alternate nuclear materials
leads to many requirements that are not met by current scientific
technologies (e.g., simple, inexpensive, low-level detection of nuclear
material in the field, differentiation of nuclear fuel versus weapon
production, etc.). Further, there is a growing need to develop a broader
and more thorough system to monitor transportation and commerce
corridors for the transport of radiological materials. Any systems
employed must address the requirements of rapid throughput,
elemental/isotopic discrimination, and low system cost. Also, for the
first responders to any terrorist incident, there must be a reliable,
cheap, "yes or no answer" approach to the detection of nuclear material.

The nuclear emission (alpha, beta, gamma) of constituent isotopes is one
of the more sensitive clues for detection of radioactive materials.
Active interrogation with neutron, electron, proton, and gamma sources
also can be used to activate some elements that are then detected by the
nuclear emission of the activated isotope. The development of more
compact, higher flux sources could enable this technology to be more
widely utilized. The field of nuclear detection has further growth
potential with the development of new sources and better (more
sensitivity, higher energy, greater spatial resolution, and room
temperature compatibility) nuclear detectors.

Another technique widely used for isotope analysis is mass spectrometry.
This technique, which depends on the method used to ionize or vaporize
the material, has extremely high resolution and can determine isotope
ratios. Mass spectrometry-based techniques can provide sensitivities
down to tens of atoms with nanometer spatial resolution by combining the
selectivity obtained via tunable laser excitation of one or more
electronic transitions with high-spatial-resolution sputtering
techniques such as ion bombardment. Such information, along with the
identification of elements and molecular speciation in particulates down
to the nanometer scale and below, should be invaluable in tracing the
origin of the material for forensic purposes. High sample throughput for
identification purposes can be achieved using high brightness x-ray
sources, such as third-generation synchrotrons, which soon are expected
to provide 50-nm spatial resolution for x-ray techniques such as
diffraction and absorption that, respectively, identify physical
structure and quantify the presence of a wide range of elements and
their local environments.

Other methods of detection for radioactive materials based on ionic
and/or molecular recognition need to be more fully developed. Although
nuclear methods indicate that an element is present, they do not provide
information about its form or oxidation state. Moreover, the sensitivity
of nuclear methods for long-lived radionuclides might not be adequate
for some applications.

Alternative detection methods could be based on the visible fluorescence
emitted under visible or ultra-violet excitation (e.g., the UO~2~^2+^
and the Cm^3+^ ion) or the infrared fluorescence emitted by the neptunyl
and plutonyl ions. The design of specific ligands that undergo a
spectral change upon binding of particular actinide ions is another
promising avenue of exploration. If color changes accompany the binding,
it is possible that specific colorimetric reagents might be designed to
indicate the presence of a particular ion. Advances in rapid element
separation using high-speed ion exchange or capillary electrophoresis
methods and new solid-state ultraviolet light sources may serve as the
basis for physically small, rapid, highly sensitive instruments for
quantifying a broad range of lanthanide and actinide elements in a few
seconds in sample solutions.

### Preparedness

Preparedness refers to the ability to respond to terrorist threats and
attacks within the U.S. If an attack cannot be prevented, efforts would
turn to response: protection of people and assets, emergency response,
and event mitigation/recovery. Measures must be in place to rapidly
identify the elements/isotopes of concern, to deal with immediate
concerns, and, ultimately, to remove these materials. Dose exposure
information must be rapidly collected and evaluated, and the appropriate
response initiated. If radioactive material is dispersed in reservoirs,
it must be identified, and emergency responders must be ready and able
to provide instructions. Methods must be available to deal with
individuals contaminated with radioactive material. Promising new
reagents are being studied for the removal of actinides from humans, but
much more work is necessary before these reagents can be utilized.
Cleanup methods and materials must be available for the removal of
radionuclides from surfaces, soils, water, and air. Agents for removal
of contaminants from soils and surfaces as well as methods for the
separation of radionuclides from air and water are necessary. Available
reagents must be evaluated and new ones developed if necessary. Modeling
of the effects of radioactive contamination in air, water, and soils
must be performed, based on reliable kinetic and thermodynamic data so
that the consequences of this type of disaster can be determined and its
effects mitigated. Finally, the question of the storage and disposal of
the radioactive material under emergency conditions needs to be
addressed.

Research related to the effect of ionizing radiation on matrix materials
may serve a dual purpose, identifying both radiation damage and also
shedding light on the utility of radiation as a decontamination measure.
Radioactive sources or accelerators that produce ionizing radiation are
used to decontaminate biological or toxicological agents from materials
by decomposing such agents into harmless products. At the same time, the
material being cleansed may also be degraded. Understanding the
fundamental processes that occur in both condensed and aqueous phases
and, most importantly, at interfaces following the passage of ionizing
radiation is necessary. In the case of a nuclear incident, the chemical
changes induced by the radiation may result in unexpected products that
make remediation difficult and dangerous. Similarly, the effects of
radiation on biological materials, although an active area of
investigation, need to be explored at the molecular level. Low-dose
thresholds (or low-dose linear responses) need to be explored at the
single molecule/single cell level.

It should be noted that as the sole agency in the federal government
with a spectrum of research activities involving nuclear and
radiological materials, the Department of Energy bears a unique
responsibility for providing the underpinning science. Preparedness
includes, in the context of the science base, maintenance of the
infrastructure (laboratories, instrumentation, computers, etc.), and
expertise (technical personnel, databases, etc.) for devising technical
solutions to the problems that might be encountered with
radiological/nuclear materials. Owing to the hazards in working with
these materials, the aging infrastructure at DOE's national laboratories
represents a particular problem for this area of research. This, coupled
with the decline in university programs designed to train actinide and
radiochemists is a particular challenge in preparing to address threats
associated with nuclear and radiological materials.

### Prevention

Another general category of threat reduction involves preventing
acquisition or utilization of the materials. Physical protection is the
first line of defense. Advanced materials could aid in the containment
of hazardous materials to prevent their dispersal upon insult (e.g.,
explosion scenarios). Physical protection of nuclear materials could be
augmented by the application of technology designed to stabilize
nuclear/radiological materials to prevent their use or dispersal. These
could include implementing advanced proliferation-resistant nuclear fuel
cycles, devising more efficient/rapid methods for the recovery and
stabilization of existing radioactive sources, and identifying improved
material forms for the storage of nuclear materials (this latter point
is increasingly important as the U.S. and Russia further reduce their
active nuclear weapon stockpiles). A related technology need is
identification of possible unconventional methods of material processing
to better anticipate possible scenarios and monitoring methods.

Prevention of a nuclear incident also depends on the interdiction of the
material or suspicious persons before entry into the U.S. This involves
inspection and detection of nuclear materials entering the country. More
sophisticated detection, as discussed previously, is clearly pertinent.
Advances in detector materials would be particularly valuable in
detecting the illicit transport of fissile or other radioactive
materials.

### Protection/Response and Recovery

If an attack cannot be prevented, efforts would turn to protection of
people and assets, emergency response, and event mitigation/recovery.
Protection against such attacks may well rely upon rapid identification
of material dispersal pathways. Strategies could be envisioned in which
critical facilities are equipped with response systems that employ
detection systems (with technology gaps similar to those discussed
above) to control building ventilation systems, or where broad-area
monitors are employed to aid in formulating evacuation routes. In some
instances, technology needs may include means of hardening
infrastructure to operate in harsh environments.

Rapid identification of the nature of the weapon by emergency responders
would be of primary concern, since the initial response would be
significantly different, depending on whether a chemical, biological, or
radiological/nuclear weapon is used. Careful post-attack analysis of
materials can also be invaluable to the identification of the
perpetrators. Attribution and the fear of a devastating response are
also powerful deterrents to attack. For a nuclear attack, determining
the specific radiological agents present in the weapon, (e.g.,
long-lived isotopes, such as U, Pu, etc., versus short-lived fission
products, such as Cs, Sr, etc.) will also dictate treatment. Current
approaches for distinguishing these characteristics often rely upon
laboratory analysis, requiring sample collection and transport.
Technology is needed to provide portable equipment for economical
chemical and radiochemical analyses of radiological materials. Finally,
technology needs exist in the design of appropriate mitigation/recovery
strategies, from prediction of migration of radiological materials
(identifying the scope of required treatment) to devising new
incident-specific solutions for broad area decontamination. Knowledge of
the interaction of nuclear materials with biological systems is also
important to develop enhanced remediation schemes and medical therapies.

## BES Research Accomplishments and Implications for Counter Terrorism

The Department of Energy (DOE) programs in radiological/nuclear
chemistry had their genesis in the Atomic Energy Commission's chemistry
research program that was built on the wartime Manhattan Project. That
program was primarily directed at the needs of the plutonium project,
and investigated chemical processes for separating uranium, plutonium,
and fission products. After the production facilities for producing and
processing plutonium were operational and successful, longer range
studies were undertaken, such as the discovery of new transplutonium
elements and chemical studies of their properties, the development of
new analytical methods, systematic spectroscopic studies of the actinide
elements, and studies of radiation chemistry. Current BES activities
have evolved from this beginning.

Short descriptions of the relevant activities in the areas of Heavy
Element Chemistry, Separations and Analysis, and Radiation Chemistry are
given below, followed by an abbreviated list of the research topics
currently studied within these activities. Other BES activities that
provide support for some radiological/nuclear issues are mentioned. A
few of the notable accomplishments of the BES activities are described.

### Heavy Element Chemistry

The BES Heavy Element Chemistry activity is the sole source of federal
support in the U.S. for fundamental research on the chemistry of the
actinides and their fission products, both of which are potential
"signatures" of activities related to proliferation and nuclear or
radiological terrorism. Relevant information developed under this
activity includes spectroscopic identification; better understanding of
the environmental chemistry (fate and transport) of actinides and
fission products; and enhanced chemical characterization methods such as
advanced x-ray spectroscopies. The supported research provides the basis
for innovative sampling and analysis technologies needed to improve the
detection and tracking of special nuclear materials; the timely
detection of a clandestine national or subnational nuclear weapons
program or noncompliance with international treaties and agreements;
advanced field and laboratory nuclear materials analysis methods; and
micro technologies for detection and analysis.

Actinide Chemistry topics include the following:

-   Fundamental research into the chemistry of f-elements, including
    thermodynamic and kinetic measurements, for improved chemical
    syntheses, characterization, and separations.

-   Fundamental research that advances the understanding and utilization
    of photon, neutron, electron, and magnetic interaction-based
    spectroscopies for chemical studies on actinide and important
    fission product species, and explores the electronic structure of
    the 5f elements.

-   Fundamental research on the coordination chemistry,
    reduction/oxidation state behavior, interfacial science, and bonding
    of the actinides, to improve understanding of their fate and
    transport, such as that mediated by sorption or partitioning at the
    mineral/water interface.

-   Research on the chemistry of f-elements in gaseous and solid states.
    Chemistry of transuranium elements on the microgram and larger
    scale.

-   Computational modeling of the molecular structure, bonding, and
    spectra of 5f element compounds.

-   Development of soft and hard x-ray synchrotron methods for element
    and species identification and characterization of local and
    extended structure.

+-----------------------------------------------------------------------+
| ![](media/image1.png){width="4.25in" height="2.31875in"}              |
|                                                                       |
| Chemical Analysis of Radionuclides                                    |
|                                                                       |
| Structural and chemical speciation information is needed to develop   |
| predictive models for the fate and transport of radionuclides and to  |
| guide the selection of cleanup technologies. While nuclear counting   |
| techniques can detect and identify the isotopic make-up of            |
| radionuclides, they provide no chemical information. BES-supported    |
| fundamental research has contributed to the development of methods to |
| characterize the speciation of actinide contaminants under a variety  |
| of conditions.^1^                                                     |
|                                                                       |
| Spectroscopic and x-ray absorption methods were used to identify the  |
| oxidation state and speciation of plutonium in wastes, structural     |
| debris, and soils at the Rocky Flats Environmental Technology Site    |
| (RFETS). Identification of plutonium oxide in soils added to a        |
| growing body of evidence that colloid and particulate transport is a  |
| dominant migration pathway for plutonium in soils at RFETS. These     |
| results guided the development of new models for protecting surface   |
| water quality. As a result of this research, technologies are         |
| available to guide our response to in radiological decontamination    |
| should it become necessary.                                           |
|                                                                       |
| *\[Los Alamos National Laboratory\]*                                  |
|                                                                       |
| > ^1^ S. D. Conradson, I. AlMahamid, D. L. Clark, N. J. Hess, E. A.   |
| > Hudson, M. P. Neu, P. D. Palmer, W. H. Runde, C. D. Tait,           |
| > "Oxidation state determination of plutonium aquo ions using x-ray   |
| > absorption spectroscopy," *Polyhedron* (1998) 17, 599-602.          |
+-----------------------------------------------------------------------+

###  Separations and Analysis 

The BES Separations and Analysis program supports research on
fundamental issues in chemical detection and associated processes for
chemical separations needed for reliable detection. Research on methods
such as particle mass spectrometry may lead to new means for identifying
elements, compounds, and particles relevant to the detection and
attribution of clandestine nuclear explosions. This research can lead to
innovative sampling and analysis technologies to improve the detection
and tracking of nuclear materials, advanced field and laboratory
radiological materials analysis methods, and micro technologies for
detection and analysis. Some of the relevant topics supported by the
activity are listed below.

-   Fundamental research on ionic liquids and supercritical liquid
    systems used for the separation of radionuclides.

-   Fundamental research on ligand systems used for the
    separation/concentration of radionuclides, a necessary first step in
    the analysis of trace amounts of elements of interest.

-   Fundamental research into atomic spectroscopy, with application to
    multi-photon and other advanced laser ionization techniques for
    ultra-sensitive elemental analysis/detection.

-   Research on the laser ablation of particulates and solids for
    quantitative chemical and isotopic analysis. (Laser-ablation
    analysis of particles on air filters is a promising method for
    determining if clandestine nuclear activities are under way.)

-   Research on the size, shape, and chemical characterization (usin*g*
    laser spectroscopic and time-of-flight mass spectrometry) of
    individual airborne particles.

-   Research on single-molecule/particle detection, micro- and
    nano-fluidic devices for chemical analysis (lab-on-a-chip).

-   Fundamental research in the use of mass spectrometry for analysis.

+-----------------------------------------------------------------------+
| Chemical Recognition and Extraction of Radionuclides                  |
|                                                                       |
| ![](media/image2.wmf){width="3.138888888888889in"                     |
| height="1.820138888888889in"}                                         |
|                                                                       |
| Environmental cleanup of radionuclides, whether because of legacy     |
| processing or in response to a terrorist event, will require the      |
| design of chemical "tweezers" that can pluck a single ion out of a    |
| host of millions or even billions of competing ions. Developing       |
| chemical-recognition principles is a critical first step in           |
| addressing this challenge. Solvent-extraction technology was recently |
| selected at the Savannah River Site for cleanup of some 31 million    |
| gallons of highly radioactive salt waste.^1^ The selected technology  |
| met the difficult processing requirements, including the ability to   |
| remove 99.9975% of the cesium from waste containing an average of     |
| only 15 ppm of cesium. The process employs the molecule shown above,  |
| known as BOBCalixC6, which had its early roots in BES-supported       |
| fundamental research in the 1970s and included the contributions of   |
| Prof. Donald Cram (University of California at Los Angles), who won a |
| Nobel Prize in 1988 for his pioneering work in the field.             |
|                                                                       |
| > ^1^ P. V. Bonnesen, L. H. Delmau, B. A. Moyer, R. A. Leonard,       |
| > *Solvent Extr. Ion Exch.* 2000, *18*, 1079-1108.                    |
|                                                                       |
| *\[Oak Ridge National Laboratory\]*                                   |
+-----------------------------------------------------------------------+

Actinide Sequestering Agents

The syntheses and characterization of actinide-specific ligands
patterned after natural iron-sequestering agents called siderophores
have received long-term support from BES.^1^ This work is based on the
recognition of the chemical similarities between Fe^3+^ and the somewhat
larger Pu^4+^ion. Expanding the coordination sphere of these synthetic
ligands and incorporation of the HOPO metal binding group have resulted
in a series of new ligands. These new compounds have been evaluated for
their efficacy in removing actinides from mice (in studies supported by
NIH). (See Figure.) Two of the newly synthesized actinide-specific HOPO
chelating agents have shown exceptional promise during the preliminary
evaluation of their efficacy for actinide decorporation (removal from
the body) and toxicity in mice. These compounds decorporate injected or
inhaled Pu and trivalent actinides much more effectively than DTPA (the
approved therapeutic drug) in all tests in mice and rats, and they have
remarkable oral efficacy.^2^

![](media/image3.wmf)

Dose effectiveness of 3,4,3-LI(1,2-HOPO) injected intraperitoneal (IP)
at one hour or 3,4,3-LI(1,2-Me-3,2-HOPO) given orally at three minutes
after an intravenous (IV) injection of ^238^Pu compared with
CaNa~3~-DTPA injected IP at one hour. The figure shows that the HOPO
ligands are much more effective than DTPA for removing Pu.

^1^ P. W. Durbin, B. Kullgren, J. Xu and K. N. Raymond. "Development of
Decorporation Agents for the Actinides," *Radiation Protection
Dosimetry* (1998) 79, 433-443.

^2^ P. W. Durbin, B. Kullgren, Jide Xu, and K. N. Raymond. "Multidentate
Hydroxypyridinonate Ligands for Pu(IV) Chelation in vivo: Comparative
Efficacy and Toxicity in Mice of Ligands Containing 1,2-HOPO or
Me-3,2,-HOPO," *Int. J. Radiat. Biol.* (2000) 76, 113-117.

+-----------------------------------------------------------------------+
| **Detecting Nuclear/Radiological Contamination of Water Supplies**    |
|                                                                       |
| Research supported by BES has led to the development of a series of   |
| novel extraction chromatographic (EXC) resins that can selectively    |
| remove one or more radionuclides from aqueous solution.^1^ The resins |
| combine a highly selective metal ion extractant in an inert polymeric |
| support. Sample solutions, adjusted to the proper acidity, are passed |
| through a series of columns packed with the appropriate resin for a   |
| particular radionuclide. The selected ions are retained on the        |
| columns, while others pass through (see Figure), and retained ions    |
| are washed from the columns for analysis. Columns with different      |
| extractants can be coupled so that multiple ions can be detected in a |
| single sample.                                                        |
|                                                                       |
| These resins can address widespread problems in radiochemical         |
| analysis and are well suited to either defining the scope and         |
| isotopic signature of contamination resulting from an incident of     |
| nuclear/radiological terrorism.                                       |
|                                                                       |
| *\[Argonne National Laboratory\]*                                     |
|                                                                       |
| ![](media/image4.wmf){width="4.565277777777778in"                     |
| height="2.9298611111111112in"}                                        |
|                                                                       |
| ^1^ M. L. Dietz, E. P. Horwitz, R. Chiarizia, \"Recent Advances in    |
| the Development of Extraction Chromatographic Materials for the       |
| Isolation of Radionuclides from Biological and Environmental          |
| Samples,\" in *Solvent Extraction for the 21st Century , Volume 1*,   |
| M. Cox, M. Hidalgo, and M. Valiente, Eds., Society of Chemical        |
| Industry: London, 2001, pp. 53-58.                                    |
+-----------------------------------------------------------------------+

###   {#section .unnumbered}

### Radiation Chemistry

BES is the sole supporter of radiation chemistry in condensed systems
(nonbiological) in the U.S. It funds specialized electron radiolysis
facilities that serve the academic research community, industrial users,
and other national laboratories. Radiation chemistry investigates the
fundamental chemical effects produced by the absorption of energy from
ionizing radiation. Although not specifically aimed at solving problems
in counter-terrorism, the fundamental knowledge developed by this
activity underlies the use of radiation sources for decontaminating
materials (e.g., mail) that harbor pathogenic organisms. This same
knowledge is applicable to the use of radiation sources for deactivating
chemical toxins by means of irradiation. Analysis in bones and teeth of
free radicals generated by radiation can reveal exposure to radiation
and determine the dose of exposure to irradiation. In the event of
nuclear terrorism or a nuclear accident, radiation effects on
contaminated materials and at contaminated sites must be taken into
account to undertake the proper mitigation measures. Some of the
relevant topics supported are listed below.

-   Radiolytic and photolytic oxidation of multifunctional compounds

-   Radiation effects in homogeneous media and multiphase systems

-   Structure and chemical properties of radiation-produced
    intermediates

-   Radiation-induced chemistry in supercritical fluids and other
    solvents

-   Radiation effects in solids

### Experimental Condensed Matter Physics 

This activity supports generic research on semiconductors, magnetic
materials, and systems that provide a science base for the development
of advanced, highly sensitive sensors and detectors, some of which may
have application for the remote detection of nuclear detonations.

### Mechanical Behavior of Materials and Radiation Effects 

This activity supports studies of the effects of irradiation on the
chemical and physical properties of materials, including a number of
ceramics that have been suggested as potential immobilization "hosts"
for surplus fissile materials in both the U.S. and Russia.

### Synchrotron and Neutron User Facilities 

The synchrotron and neutron facilities provide a unique set of
analytical tools for characterization of materials at the atomic and
molecular level. These tools determine the atomic constituents of
materials, the positions of the atoms in materials, and the behavior of
materials under the influence of external perturbations such as
radiation or chemical attack. Various experimental and theoretical tools
are available for the nondestructive detection and identification of
radiochemical species that might occur after a terrorist event.

### Geosciences

Geophysics research focuses on improving subsurface imaging, which
includes a large component involved with understanding how seismic waves
are generated and then propagate through anisotropic, heterogeneous
earth materials. This work can improve capabilities to account for the
environment's effects on seismic observables. This is important for the
interpretation of both teleseismic and near-field seismic data in terms
of the source mechanics. Indirectly, this work has an impact on the
ability to use regionally based seismic monitoring methods to detect
very low yield events that might arise from a clandestine testing of
nuclear devices.

Geochemistry research focuses on studies of the interaction of minerals
and mineral surfaces with water. This knowledge is relevant to the
determination of the fate and transport of radionuclides in the
environment as well as the long-term stability of nuclear wasteforms
with respect to aqueous corrosion/dissolution after they have been
emplaced in a geologic repository. The Geosciences program also supports
research in analytical methods that can be used for trace measurements
of isotopes for geological dating. These same methods may be used for
determining isotopic ratios in forensic analyses.

+-----------------------------------------------------------------------+
| ![](media/image5.jpeg){width="3.375in" height="1.9715277777777778in"} |
|                                                                       |
| Scientific Analysis Alleviates Public Concern over the\               |
| Three Mile Island Reactor Vessel                                      |
|                                                                       |
| On March 30, 1979, two days after the accident in the Three Mile      |
| Island Reactor, press reported the existence of a noncondensable      |
| bubble in the reactor vessel. This bubble was said to consist mainly  |
| of hydrogen, and the danger of explosion was reported to be imminent. |
| BES scientists analyzed^1^ all possible sources of noncondensable     |
| gases including radiolysis, and it was determined that a continuing   |
| growth of the bubble during several days after the accident was not   |
| possible. In addition, they were able to show that the bubble did not |
| contain a combustible mixture. The tools and capabilities of basic    |
| research will also play an important role in guiding our response and |
| public education surrounding future possible acts of                  |
| radiological/nuclear terrorism.                                       |
|                                                                       |
| ^1^ S. Gordon, K. H. Schmitt, and J. R. Honekamp, *Radiat. Phys.      |
| Chem.* 21, 247-258 (1983).                                            |
+-----------------------------------------------------------------------+

Forensic Analysis of Radiological Materials

BES-funded research into the fundamental chemistry of mass spectrometry
has helped lay the foundation for ultra-sensitive isotope analysis
techniques. Investigations into ionization and gas phase ion processes
have led to the development of ultra-sensitive thermal ionization mass
spectrometry for isotope analysis and high-precision, high-accuracy
secondary ionization mass spectrometry for the analysis of isotope
ratios in situ with high spatial resolution (see photo). Finally,
improvements in chemical separation and analysis of radionuclides (U,
Pu) using electrochemically modulated separation combined with MS show
potential for rapid screening of physiological media, such as urine,
with a minimum of sample preparation. The isotopic data, as well as
elemental proportions, could be used to detect nuclear activity and to
fingerprint the source of nuclear materials that may be part of a
terrorism event.

![](media/image6.png)*\[Oak Ridge National Laboratory\]*

## Scientific Issues and Research Opportunities

Fundamental scientific challenges must be overcome to achieve new and
improved technologies that effectively counter radiological and nuclear
threats. Here some of the problems with current capabilities and
techniques are defined more precisely. The underlying issues that must
be addressed to resolve homeland security deficiencies are identified,
and the opportunities for innovation in solving these problems are
cited.

### Detection

  ----------------------------------- -----------------------------------
  **Technology Need**                 **Present Problem**

  Rapid, reliable, simple, cheap      Current detectors are expensive and
  radiation detectors for first       moderately complicated.
  responders.                         

  Field deployable, moderate to high  Current detectors are delicate and
  resolution, radiation measurement   require cryogenic temperatures to
  instrumentation.                    obtain energy-resolved spectra.
  ----------------------------------- -----------------------------------

##  {#section-1 .unnumbered}

Radiation measurements are hampered by the limitations of available
materials. There are different problems with the two main classes of
materials.

#### Scintillators {#scintillators .unnumbered}

The first major class of radiation-detecting materials provides rather
limited energy resolution such as scintillators or ambient-temperature
semiconductor gamma detectors, such as cadmium zinc telluride (CdZnTe).
These materials are likely to be most useful for a first responder,
large-area detector system, or ultraminature instrument applications. A
scintillator converts ionizing radiation or absorbed neutrons into light
that is then measured with a photosensor.

Many types of scintillators are available. Their principal limitations
are poor energy resolution and lower than desired quantum efficiency.
This provides a significant research opportunity because improved energy
resolution or better conversion of the energy carried by a high-energy
photon or neutron into multiple lower energy scintillator photons offers
the possibility of large gains in overall detector efficiency.
Currently, CdZnTe is comparatively expensive, and its cadmium content
presents environmental hazards upon disposal. Lower cost synthesis of
similar but less hazardous materials is desired. Development of
large-area, multiple-detector "blanket" systems for contact use in rapid
assessment of low-level surface contamination during environmental
cleanup following a radiological or nuclear incident is a concept worth
assessing if the cost of needed sensors and signal electronics can be
lowered sufficiently.

#### Semiconductor-Based Materials {#semiconductor-based-materials .unnumbered}

The second class of materials used for radiation measurement provides
high energy resolution. These are typically semiconductor-based, such as
lithium-drifted germanium (Ge(Li)). These detectors efficiently convert
incident ionizing radiation into electron-hole pairs that are then
detected using conventional electronics.

The principal limitations of these materials are their cost,
availability, and, in the case of Ge(Li) commonly used for
high-resolution gamma detection, the cryogenic temperature essential for
optimum performance. Large-volume detectors of this class are quite
expensive because of the difficulty in synthesis and fabrication.
Development of improved pixel-based detectors, better
surface-passivation techniques to increase the reliability of materials,
and lower cost synthesis methods present significant opportunities for
achieving cost-effective improvements in detection systems.
High-resolution gamma detectors that operate at temperatures
significantly higher than 77 K are desirable for field detection or
portable instrument applications. High-energy x-ray and gamma lenses
offer a means of significantly enhancing detection of radionuclides at a
distance for a given detector volume and are useful in imaging of
radionuclide sources. However, such lenses are currently handcrafted and
are expensive.

  ----------------------------------- -----------------------------------
  **Technology Need**                 **Present Problem**

  Combined sensors to determine       Such integrated systems do not
  nature of threat (e.g*.,* high      exist, and both types of detection
  explosives and radioactive material systems currently have sensitivity
  or radioactive material alone).     limitations.

  Improved methods for remote imaging Current methods for large-object
  of radioactive sources contained    tomography are not suitable for
  within large objects such as cargo  routine surveillance.
  containers, ships, or trucks.       

  Stand-off detection of shielded     Current active interrogation
  nuclear materials.                  systems are incompatible with some
                                      cargo, and are not portable.
  ----------------------------------- -----------------------------------

Radionuclide sensing via active methods involves irradiation of the
suspect material with photons or subatomic particles, such as neutrons,
and assessing the response of that material, such as absorption of an
incident photon or emission of neutrons because of induced nuclear
fission, to the irradiation field. Some of these active interrogation
methods have the potential to detect the presence of
light-element--based high explosives as well as most actinide elements.
However, absent improved detectors, the intensity of irradiation field
needed may damage or destroy plants, animals, and materials. In
addition, some suitable irradiation sources are not readily portable
(e.g., proton accelerators). Methods for low-cost fabrication of
high-power mm RF components would be enable creation of portable ("table
top") accelerators. Similarly, advances in femtosecond laser technology
would advance "table top" electron accelerator technology. Further
development of electrically powered, portable neutron generators would
advance detection of fissile materials in transit at border checkpoints
and transportation hubs.

  ----------------------------------- -----------------------------------
  **Technology Need**                 **Present Problem**

  Rapid characterization of aerosol   Remote interrogation of a suspect
  plumes that might contain           plume to obtain elemental
  radionuclides.                      composition and particle size
                                      distribution for most radionuclide
                                      species has not been assessed.
  ----------------------------------- -----------------------------------

Remote laser sensing offers controlled illumination over distances from
meters to kilometers, high spectral selectivity, and high-speed
operability. Of particular importance is the issue of detection of
signatures from specific radioactive materials. Some other subatomic
particles, such as neutrinos, provide very high penetration but are
difficult to detect by simple means. Obtaining significant improvement
in the generation, collimation, and high-sensitivity detection of such
particles is distinctly challenging and could represent the desired
breakthrough for safe application of large-object tomography. In
addition, improved broadband (femtosecond pulse) sources may have
significant utility in longer range aerosol remote sensing.

  ----------------------------------- -----------------------------------
  **Technology Need**                 **Present Problem**

  Ultratrace to single-atom detection Current methods are relatively slow
  of a broad range of elements and    and generally have sensitivities
  isotopes together with chemical,    measured in many thousands of atoms
  physical, and structural            and poor spatial resolution.
  characterization of sample          Typically, extensive sample
  materials for attribution and       pretreatment is required prior to
  intelligence-gathering purposes.    analysis.
  ----------------------------------- -----------------------------------

Samples of plant, animal, or mineral materials or manufactured articles
differ as to their trace element and isotope content, depending on their
origin. Detection of trace constituents indicative of the production of
fissile isotopes or having unusual relative isotope abundances of
hydrogen or lithium isotopes, for example, can provide an early warning
indicator of proliferation activities and, if associated with additional
trace indicators, the location of those activities.

Further development of ultratrace analysis techniques is essential to
achieve high sample throughput and spatial resolution with broad
elemental applicability, high isotopic discrimination, and minimal
sample pretreatment. High-spatial-resolution chemical, physical, and
structural characterization of samples provides additional bases for
differentiating materials and determining their probable origins.
Development of existing surface enhanced vibrational spectroscopies
(e.g., surface enhanced Raman) combined with high-efficiency,
solid-state laser microscopies may provide both the needed chemical
speciation and imaging capabilities down to the single molecule level.
Further development of electron and ion microscopies and analysis
techniques based on x-ray beams focused to nanometer dimension may also
provide these required characterization capabilities.

### Preparedness

  ----------------------------------- -----------------------------------
  **Technology Need**                 **Present Problem**

  Containment of widespread           First responders and others need
  radioactive contamination caused by training in this area and supplies
  a terrorist event.                  for detecting, containing,
                                      immobilizing, and removing
                                      contamination.

  Maintain critical infrastructure    Decaying infrastructure and limited
  and appropriately trained           education and training
  personnel.                          opportunities.
  ----------------------------------- -----------------------------------

Containment and prevention of isotope migration will be of immediate
concern following a terrorist release of radionuclides. Effort is needed
to develop rapidly deployable immobilizing agents that can be applied to
contaminated soils, buildings, vehicles, etc. Whereas these could be
comprised of nonreactive materials (i.e., urethane foams or other rapid
forming plastics), such immobilizing agents would ideally facilitate
cleanup and removal of the radionuclides following the initial response
to a terrorist event. This may be facilitated by inclusion of sorbents
within a permeable coating. Finally, one might choose a foam composition
that would induce the reduction of high-valent actinides to less soluble
lower oxidation states or a foam composition that leads to a significant
increase in soil pH, resulting in the precipitation of radionuclides as
hydroxides or oxides. To date, none of these selective immobilizing
agents exists. Fundamental work is needed in the areas of polymer
chemistry and separations chemistry to realize the potential of this
approach. Furthermore, it is imperative that personnel be trained to
detect radioactive materials and to react appropriately in the case of
nuclear terrorism.

  ----------------------------------- -----------------------------------
  **Technology Need**                 **Present Problem**

  Effective therapies needed for      The current treatment method for
  decontaminating victims of          actinide removal is limited in its
  radioactive contamination,          efficacy
  especially for actinide             
  contamination.                      
  ----------------------------------- -----------------------------------

Actinide, especially plutonium, contamination is a significant danger
because of its high toxicity. The currently accepted method for reducing
and removing Pu in the body consists of intravenous or inhalation
administration of the chelating agent DTPA,
diethylenetriaminepentaacetic acid. This protocol has significant
therapeutic limitations and is inadequate for treatment of the general
public. Possible new compounds for actinide removal have shown great
efficacy for actinide ions at physiological pH. They are based on the
syntheses and characterization of a number of actinide-specific ligands,
patterned after natural iron-sequestering agents called siderophores.
These compounds have been evaluated for their efficacy in removing
actinides from mice (in studies supported by NIH). However, many
additional studies are necessary before these new materials can be
certified for drug use. A more effective treatment for the decorporation
of actinides in case of human contamination is clearly a highly
desirable goal for the mitigation of a possible terrorist act.

### Prevention

  ----------------------------------- -----------------------------------
  **Technology Need**                 **Present Problem**

  Stabilization of nuclear materials  Radioactive material inventories
  against dispersal.                  are increasing, and safe and secure
                                      storage of these isotopes is
                                      required.
  ----------------------------------- -----------------------------------

Much research has been devoted to the materials science of the actinide
elements, especially plutonium, over the last fifty years. Many types of
complexes have been investigated for use in the nuclear fuel cycle as
well as for use for safe and secure storage of special nuclear
materials. The oxides of uranium and plutonium have received the most
study and are the materials commonly found in nuclear fuels, including
the mixed oxide fuels (MOX). MOX fuels are being seriously considered
for disposal of excess weapons plutonium in both Russia and the U.S.^4^
Plutonium is commonly stored as PuO~2~, since in this form it is highly
insoluble.

In the future, the synthesis of highly refractory actinide materials
that are stable to moisture, are highly dense, can be produced at
moderate temperatures, and have a number of desirable physical
characteristics for nonproliferation such as the presence of neutron
poisons will increase the safety and reliability of storage systems. A
major obstacle to the widespread production of these types of actinide
materials relates to the reaction temperatures, which range as high as
3000 °C to achieve high purity.

Research in this area should emphasize the development and
implementation of unique reaction conditions and novel precursors that
enable the preparation of materials at lower temperatures (500--750 °C)
and pressures. Such research could also be of value to the development
of advanced nuclear fuels that could be easily reprocessed but are
difficult to convert to weapons-grade materials. The combination of
solid-state, homogenous molecular, and/or vapor-phase deposition
synthetic chemistry with multidisciplinary analytical and spectroscopic
characterization is needed to produce such new materials. Their
production could be a major factor in decreasing the likelihood of
diversion for terrorist activities because of the difficulty to use such
materials for terrorist purposes.

  ----------------------------------- -----------------------------------
  **Technology Need**                 **Present Problem**

  Understanding of alternative        Unconventional nuclear materials
  process chemistry,                  processing may not be detected by
  proliferation-resistant fuel        current methods.
  cycles.                             
  ----------------------------------- -----------------------------------

Awareness of chemical agents that could be used in the purification of
Pu and U for use in terrorist activities either from nuclear weapons or
from irradiated fuel could be an important signature to prevent their
use in terrorist attacks. Universally, the standard purification method
for U and Pu has been the Purex process, which uses tributyl phosphate
as a solvent extractant. Large-scale purchases of this material would
immediately be a source of concern. However, it is likely that terrorist
groups who might attempt to use these materials would use alternate
processes with different materials. Knowledge of these alternate
materials and processes would enhance intelligence activities.

There is significant activity internationally on alternate processing
systems for irradiated nuclear fuel. These include aqueous systems as
well as nonaqueous separation systems, volatility methods, and other
advanced concepts. The technological requirements for further
advancements in this field include synthesis, and testing and
characterization of new separation methods with particular emphasis on
the isolation and purification of the actinide elements.

An example of the potential basis for new actinide separations systems
is neoteric solvents, such as ionic liquids, supercritical carbon
dioxide, or fluorous phases, that can be considered new classes of
solvents for targeted dissolution and separation of transuranic
elements. Such new processing conditions represent several fundamental
unknowns. Use of these solvents may lead to unique signatures that are
valuable in identifying and locating process sources; the solvents may
lead to cheaper, better, cleaner processing and/or separations; or there
may be unique chemistries not possible through traditional solvent
routes.

Actinide speciation and coordination in many neoteric solvents are
unknown, but knowledge of speciation and coordination is essential in
optimizing separation schemes. Solvent characteristics such as thermal
stability, radiolytic stability, and heat capacity are for the most part
unknown. These characteristics need to be determined for fundamental
chemistry and separations purposes. Understanding neoteric solvent-based
separations may result in improved methods for separating and purifying
actinide elements. It also will aid in identification of unique
signatures of reprocessing via this method, if such signatures exist.

The knowledge base that results from basic research studies on
separations and heavy element chemistry is an important component in the
identification and tracking of new methods for reprocessing of nuclear
fuel and the early discovery of such reprocessing should it be attempted
clandestinely for terrorism purposes.

### Protection/Response and Recovery

+-----------------------------------+----------------------------------+
| **Technology Need**               | **Present Problem**              |
+-----------------------------------+----------------------------------+
| > Identification of the chemical  | Insufficient knowledge of        |
| > and physical form of a          | chemical signatures, low signal  |
| > contaminant.                    | for widely dispersed material,   |
|                                   | needed information for           |
|                                   | predicting fate and transport    |
|                                   | not available.                   |
+-----------------------------------+----------------------------------+

Environmental sampling and analysis of elements and isotopes diagnostic
of the isotope enrichment processes needed for production of nuclear
materials are a key means of detecting nuclear threats. River water
samples, atmospheric aerosol samples, and other water source sampling
may all contain elemental and isotopic signatures diagnostic of nuclear
proliferation. Either the radionuclides themselves (e.g., U-235, Np-237,
Pu-239, etc.) or byproducts of the enrichment process (e.g., fission
products) can be detected in the environment with ultra-low detection
limits using chemical or geochemical sampling protocols and analytical
instrumentation.

Sampling protocols have been developed for sediments and waters to
support environmental restoration efforts, and the general analytical
framework to analyze samples is understood.^5^ Limitations exist,
however, that are principally associated with sensitivity, speed and
throughput, fieldability for on-site response, and integration of
existing archived data with analytical tools to assist calibration and
interpretation. Research objectives associated with these technology
gaps include development of new instrumental approaches. Research into
the processes that control the fundamental signatures in environmental
substrates, governing the correlation between agents and sources, would
be one of the prerequisites to developing new methods.

+-----------------------------------+----------------------------------+
| **Technology Need**               | **Present Problem**              |
+-----------------------------------+----------------------------------+
| > Develop clean-up strategies for | Initial sorption processes       |
| > deployment after a terrorist    | resulting from a terrorist event |
| > event involving radioactive     | are kinetically driven. Better   |
| > materials.                      | knowledge of fundamental         |
|                                   | equilibrium chemistry, radiation |
|                                   | chemistry, and kinetics of       |
|                                   | chemical reactions involving     |
|                                   | radionuclides (for improved      |
|                                   | predictions for during response  |
|                                   | and cleanup) are needed.         |
+-----------------------------------+----------------------------------+

If nuclear materials are dispersed through a terrorist act, large areas
at or near the site will become contaminated. Research efforts on
fundamental science relevant to the cleanup of radionuclides have been
supported by BES. Additional research is being conducted in DOE's EMSP
program. However, these research efforts have been focused on
development of information for the cleanup of historical, or "aged,"
contamination problems, which are not likely relevant to the cleanup of
recently contaminated sites.

The recent development of new molecular-level spectroscopic methods is
providing unprecedented opportunities to explore interfacial processes,
in many cases in real time. These techniques enable study of the
dynamics of highly specific interactions at surfaces. They include
scanning probe microscopy (SPM), x-ray absorption spectroscopies (XAS)
with microscale spatial resolution, laser microscopy, scanning electron
microscopy (SEM), high-resolution transmission electron microscopy
(HRTEM), and electron microprobe (EM) methods. An ever-increasing body
of evidence from these methods demonstrates that radionuclide sorption
at the mineral-water interface begins with specific molecular-level
interactions. These are the chemical reactions that scale up to yield
the macroscopic interfacial phenomena observed in the environment and,
ideally, can be predicted with geochemical models. Confidence in such
predictions can be improved by a mechanistic understanding of these
molecular reactions and their representation as equilibrium
thermodynamic or kinetic expressions in such models.

Aged contamination represents an established steady state that has
developed over time following the initial sorption. The sorption
processes that are relevant following a terrorist event are more likely
kinetically driven. To address these science needs, research should
focus on defining the initial kinetic processes and the mechanisms
whereby radionuclides are sorbed to environmental matrices. The tools
described above should make this possible. This information will be
essential in developing clean-up strategies for deployment after a
terrorist event involving nuclear materials.

Beyond identification of the mechanisms of sorption and transport,
research is required on treatment methods appropriate to immobilize or
mobilize contaminants in a controlled fashion with minimal disruption to
the host matrix. Understanding of interfacial redox and complexation
chemistry is distinct from traditional solution process chemistry, but
will be key to successful development of new clean-up protocols.

To the extent that the application of separation science to counter
terrorism involves the isolation, separation, or preconcentration of
radioactive metal ions, the general research needs identified are the
following:

-   Development of highly specific ligands, allowing separations to be
    performed in fewer steps, with smaller equipment, or with lesser
    volumes of reagents, and cost-effective methods for their synthesis.

-   Development and application of improved computational methods for
    ligand design.

-   Application of parallel synthesis technologies and combinatorial
    methods to the preparation and evaluation of new ligands.

-   Improved understanding of the thermodynamics and kinetics of
    solute-solvent interactions, permitting selection of the most
    appropriate separation medium (solvent, ion-exchange resin,
    membrane) and offering additional opportunities to increase process
    efficiency.

-   Greater consideration of complexation and mass transfer kinetics in
    the design of extractants and complexing agents.

-   Application of modern experimental (e.g*.*, synchrotron radiation
    sources) and theoretical (molecular dynamics calculations)
    methodology to the development of an improved understanding of the
    properties of liquid-liquid and liquid-solid interfaces, thus
    providing new perspectives on the nature of separations-relevant
    processes occurring at these interfaces.

-   Development of environmentally benign separation processes, which
    produce no secondary wastes and consume no chemicals.

+-----------------------------------+----------------------------------+
| **Technology Need**               | **Present Problem**              |
+-----------------------------------+----------------------------------+
| > Better understanding of         | Insufficient knowledge of        |
| > radiation effects on            | chemical consequences of         |
| > environmental materials.        | irradiation of environmentally   |
|                                   | exposed materials.               |
+-----------------------------------+----------------------------------+

To mitigate the chemical consequences of radioactive contamination in
the environment, predictive models are required. Much is known about the
fundamental radiation effects in homogeneous systems of common
materials. However, the chemical effects of ionizing radiation on
complex, heterogeneous environments are largely unknown.

Fundamental information on the time evolution of events following the
absorption of radiation by complex materials and at interfaces is,
therefore, needed. The absorption of radiation in complex materials
changes the chemical and physical properties of the material. This is
particularly important in systems that are common in the natural
environment. Oxidation state, surface potential, lattice parameters,
reactive site density, solubility, particle size and size distribution
of soil particles, humic substances, minerals, metal ions, etc., will
all change as a result of the radiolytic processes and affect the
mobility and migration of radionuclides in the environment. In a
terrorist attack involving nuclear incidents, components of sensors
(optical materials, semiconductors, plastics, etc.), which are sensitive
to radiolytic effects, will suffer significant performance
deterioration. These can be modeled, and remedies may be offered if
fundamental information on the effects of radiation is available.
Studies should include not only electron and gamma irradiation, but also
the effects of alpha particles and neutrons. Ionizing radiation is one
of the available methods for preventing the spread of lethal bioagents
via sterilization. Improving the efficiency of the sterilization process
and minimizing adverse side products are significant challenges.
Existing machines use electron beams whose penetration depth is
relatively limited. Scenarios should be developed to enhance penetration
depth, and thereby the efficiency of the sterilization process. At the
high doses required for sterilization, the object itself may be damaged.
This not only destroys the object, but may also release noxious gases,
which may harm the personnel handling the materials. Fundamental
studies, experimental and computational, will identify and quantify the
risks from using ionizing radiation and develop strategies to minimize
them.

## Research Needs

The preceding sections have identified a number of scientific issues and
research needs than can have significant impact in addressing critical
problems associated with countering radiological and nuclear threats.
The following are some of the most critical issues that were identified

### 2.4.1 Scientific Issues {#scientific-issues .unnumbered}

#### Chemical Separations {#chemical-separations .unnumbered}

Chemical separations will play an important role in delineating the
scope of contamination, mitigating the damage, and facilitating recovery
from a terrorist event. Continued research is required on critical
issues including the isolation, separation, or preconcentration of
radioactive metal ions. In addition, resources should be directed toward
the development of environmentally benign separation processes that
produce no secondary wastes and consume no chemicals.

#### Ion/Molecular Recognition {#ionmolecular-recognition .unnumbered}

Selective ligands for actinides and fission products will play a key
role in technologies associated with detection, prevention, and response
and recovery. Combinatorial chemistry approaches should be used to aid
in the design of new receptors. In addition, new approaches for modeling
and characterizing the thermodynamics and kinetics of
radionuclide-ligand interaction will help to accelerate the development
of more effective ligands.

#### Interfacial Science {#interfacial-science .unnumbered}

There is a significant need to describe the behavior of actinides in
more complex media, often involving nonequilibrium conditions, and
chemical speciation/distribution at interfaces (solid/solution, aqueous
phase/biological membrane, etc.). Research should seek to establish the
nature of chemical processes, including those between actinides and
fission products and reactive surfaces. This will require the
development of new probes to characterize kinetic, thermodynamic, and
structural elements at surfaces.

#### Computing, Modeling, and Simulation {#computing-modeling-and-simulation .unnumbered}

It will be critical to develop improved algorithms and computing
platforms to provide accurate predictions for nuclear, atomic,
molecular, and macromolecular properties and interactions. Important
areas for such calculations are as diverse as determining the influence
of hyperfine, electrostatic, and magnetic interactions on atomic and
ionic spectra of actinide isotopes to improving the design of novel
scintillator materials. Insight gained from theoretical calculations
must be integrated into the planning, execution, and analysis of
experiments, particularly those designed to assess new approaches to
countering terrorism.

#### Advanced Instrumentation/ Laser and Mass Spectroscopy {#advanced-instrumentation-laser-and-mass-spectroscopy .unnumbered}

Many of the advanced instrumentation needs that were identified, such as
large-area tomography, will have to be addressed by multidisciplinary
research teams of scientists and engineers. The continued development of
high-sensitivity spectroscopic tools will underpin research efforts in
chemical speciation of actinide and fission products under a variety of
conditions. Advances in laser-based techniques are needed for improved
stand-off detection, while improvements in the performance of
conventional mass spectrometry instruments are needed to address the
broad range of isotopes and elements that need to be quantified.

#### Novel Materials {#novel-materials .unnumbered}

Combinatorial chemistry or other rapid synthesis and assessment
techniques along with insight gained from theoretical calculations
should be employed to improve scintillator performance. The same methods
can also be applied to ligand design for specific ion separations.
Research in actinide materials is required to address technology needs
in material stabilization.

#### Alternative Processing Chemistry {#alternative-processing-chemistry .unnumbered}

Fundamental research in physical and chemical separation methods,
chemistry in alternative media (including nonaqueous), and methods for
isotopic enrichment, is needed to understand the possibilities for
alternative processing of nuclear materials and their potential for
affecting nuclear proliferation. This research might also lead to the
development of new processes that have significant advantages over our
current technologies.

### Research Environment and Infrastructure

The DOE is the only source of funding for fundamental and applied
research studies involving radiation effects and nuclear and
radiological materials. The Office of Science has the stewardship role
for fundamental research in these areas. However, the resources
allocated to these areas have, in general, been decreasing over the last
three decades. This has resulted in a net loss of personnel and aging
infrastructure, including a lack of modern equipment. These problems are
not only acute at the national laboratories, but are also reflected at
universities where faculty positions and studies in radiochemistry and
nuclear chemistry have been rapidly declining.

Most of the buildings and facilities at the national laboratories used
for fundamental research with radioactive materials were built more than
thirty years ago. Upgrading and modernizing these facilities is
necessary to bring them to modern day standards and also to implement
new research tools to advance fundamental research in heavy element
chemistry and physics and the effects of radiation. This is an essential
first step necessary to re-invigorate the national laboratories.
Collaborative efforts or virtual conferencing should be encouraged to
facilitate productive interaction among geographically diverse team
members.

#### Education and Training {#education-and-training .unnumbered}

The key need for all areas of Homeland Security is trained personnel.
For the Radiological / Nuclear Threats area, this means that personnel
trends in both university and national laboratory programs must be
reversed for DOE to maintain a cadre of qualified scientists and
personnel that can address radiological technical issues and threats now
and into the future. With the realization that nuclear power represents,
at least at present, the only major source of energy without the
production of carbon dioxide, it is even more critical to attack the
personnel and infrastructure problems that can greatly handicap future
programs. In addition, the further development of nuclear power,
although it brings the risk of terrorist attacks, reduces the dependence
of the U.S. on foreign sources of oil and the risk of the U.S. being
held "hostage" by foreign oil-producing nations.

Although radio and nuclear chemistry was an active research area at many
universities, the facilities to conduct radiochemical research and
education at universities are either disappearing or have aged beyond a
useful stage. Furthermore, whereas aspects of nuclear science and
nuclear engineering were once considered an important part of the
general science and engineering curricula, others, perceived to be of
more general interest, have replaced these subjects. Without the
infrastructure to educate science and engineering undergraduates in
nuclear science and engineering, the general population becomes
increasingly ignorant of the risks associated with a radiological or
nuclear attack and will not understand response efforts.

The supply of trained radiochemists is seriously impeded by the lack of
facilities at universities to conduct research and teaching in this
area. University radiochemistry programs also provide an additional
source of novel ideas and research agendas to complement those at the
national laboratories. Without an incentive for adequate infrastructure
within the educational system, the universities will continue to close
the few remaining programs in nuclear science and engineering, and the
knowledge base in radiochemistry and actinide science, and the ability
to respond to threats will be eroded. Applications of radiochemistry
and, to some extent, actinide chemistry extend not only to defense
programs, nuclear energy, and counter terrorism, but also to areas more
attractive to the general public such as environmental cleanup and
nuclear medicine (e.g., advances in cancer treatment and diagnosis).

One attractive concept is to augment the national laboratory programs
and facilities that deal with radiation chemistry and heavy element
chemistry and physics by creating regional centers (with national
coordination) that can act as user facilities for university programs.
The model for this type of center is the user facilities and programs at
DOE's synchrotron sources. In this scenario, the national laboratories
will provide materials, training, facilities, and instrumentation for
visiting researchers to be able to come to the center and perform
experiments with materials or equipment not available at their
institutions. Part of the staff at the national laboratory will be
responsible for training these visitors and facilitating their
experiments. At the same time, universities should extend their training
and research in these areas with courses taught by national laboratory
personnel in their specialty science areas to supplement the traditional
university radiochemistry programs.

To help universities initiate and/or continue their programs in nuclear
and radiochemistry, DOE should consider the award of start-up funds for
newly appointed and established faculty in research areas that are
determined to be in the national interest. Such grants might be for five
years and renewable based upon peer review. These faculty and their
students could collaborate with the national laboratory regional centers
to avoid duplication of resources and to strengthen the ties between
academia and the national laboratories. Clearly, such programs would
benefit DOE and the U.S. by providing qualified scientists and personnel
to pursue future radiological/nuclear issues.

#### BES-Supported User Facilities {#bes-supported-user-facilities .unnumbered}

Over the last several years, both national laboratory and university
researchers have successfully capitalized on the ability to perform
experiments with radioactive materials at many of the BES-supported user
facilities. This is particularly true at the synchrotron radiation light
sources, where significant experiments contributing to the understanding
of both fundamental and applied aspects of radiological materials
relevant to issues of homeland security have been performed.

Many of the user facilities are situated at national laboratories or at
DOE centers that have sufficient infrastructure and experience handling
radioactive materials in accordance with DOE standards to permit and
support a reasonable number of such activities. However, to facilitate
more efficient and productive scientific investigations of radioactive
materials, as well as to engage a larger community of users, additional
operational support for these studies is necessary, especially since the
safety aspects are an integral and time-consuming component of the
experiments. Furthermore, having the ability to capably handle materials
close to the user facilities is also important, and the need for support
of these "satellite" user facility laboratories should be recognized. An
increased level of operational support for the use of radioactive
materials, at least in the case of synchrotron radiation sources, will
also allow utilization of a larger number of synchrotron radiation
techniques.

### 2.4.3 Relationships with Other Programs {#relationships-with-other-programs .unnumbered}

DOE is the only source of funding for fundamental radiological and
radiation chemistry because of its role in nuclear weapons design,
manufacturing, and stewardship, as well as in managing the environmental
legacy of weapons production. Strong scientific ties exist between core
BES programs and the Environmental Management Science Program (EMSP),
particularly in areas relating to the development of chemistry for waste
treatment or diagnostics of chemical behavior. It is important to note
that these specific areas have been cited as research needs in the
context of counter terrorism. Technologies derived from BES-funded
research are now beginning to find interest in appropriate NNSA
programs. Certainly research investment in analytical tools (e.g., mass
spectrometry) has been and will continue to be a vital contribution to
programs in radiochemical analysis sponsored by DOE -- National Nuclear
Security Administration (NNSA) and a variety of other federal agencies.

Strong interests exists between research in heavy element and radiation
chemistry and Defense Programs activities within the NNSA. Historically,
BES-sponsored programs have been integral to the development of process
chemistry for the chemical and isotopic separation of actinides. More
recently, these programs are playing a significant role in the
development of tools to investigate chemical and structural properties
of materials related to weapons components, including the effects of
aging and radiolysis. This has led to the development of new
partnerships between NNSA laboratories and user facilities supported by
BES.

New relationships are likely to develop as a function of increased
emphasis on relevant research areas within BES. For example, as research
is expanded to include a greater role for fission product research,
overlap will be strengthened with technical interests in BER and DOE-NE
(e.g., NE-70, the Office of Isotopes for Medicine and Science). These
include mutual interest in the biological chemistry and coordination
chemistry of radionuclides, as well as the development of novel
separations methods for purification and isolation. It is significant to
note that interactions are increasing between DOE laboratory programs in
heavy element chemistry and university-based programs in radiochemistry.
These collaborations are encouraged in principle through the Office of
Nuclear Energy through programs such as the Advanced Nuclear Medicine
Initiative (ANMI) and the Innovations in Nuclear Infrastructure and
Education (INIE) initiative. While these do not specifically fund work
in counter terrorism, they may support the infrastructure and training
needs (as cited above).

### 2.4.4 Dual-Use Opportunities {#dual-use-opportunities .unnumbered}

The knowledge to be gained from these and associated research programs
will not only hold value in countering terrorism, but can make
contributions to many other technology areas. For example, improvements
in radiation detection schemes or materials for radiation detection
would be beneficial in a range of applications from medical diagnostics
to astrophysics research. Improved understanding of chemistry in complex
matrices has already been highlighted as a research topic that can bring
great benefit to the DOE complex in meeting its responsibilities for
long-term stewardship at a number of contaminated facilities and at
waste repository sites. Improved knowledge of process and materials
chemistry will be integral to the implementation of advanced nuclear
fuel cycles, and will equally contribute to solving problems in
materials stabilization or disposition. Through examination of
interfacial and materials chemistry, this research will also devise new
scientific tools suited to addressing technical questions in one of the
primary missions of the DOE: stewardship of the nation's nuclear
stockpile (in particular, examination of the effects of aging on key
materials). Finally, it has long been recognized that the scientific
infrastructure associated with actinide and fission product research
within the DOE is very similar to that required for further development
of nuclear medicine. This is recognized directly in the DOE-funded
summer nuclear chemistry schools, as well as in the curricula of a
number of university departments emphasizing nuclear and radiochemistry.
This overlap will become even more significant in the event that
BES-sponsored research can be expanded to include more research on
fission products.

^\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_^

^1^ See for example J. Warrick, "Making of a 'Dirty Bomb'," *Washington
Post*, March 18, 2002, page 1; J. Glanz, "Despite New Tools, Detecting
Nuclear Materials Is Doubtful," *New York Times*, March 18, 2002, page
13.

^2^ "Proliferation concerns: assessing U.S. efforts to help contain
nuclear and other dangerous materials and technologies in the former
Soviet Union," National Research Council (U.S.), Office of International
Affairs, Washington, D.C., National Academy Press, 1997.

^3^ "Technology R&D for Arms Control," Arms Control and Nonproliferation
Technologies, Office of Nonproliferation Research and Engineering,
National Nuclear Security Agency, Defense Nuclear Nonproliferation
Program, Spring 2001, http://www.llnl.gov/nai/communication.html.

^4^ "Mixed Oxide Fuel (MOX) Exploitation and Destruction in Power
Reactors," Proceedings of the NATO Advanced Research Workshop, Obninsk,
Russia, October 16--19, 1994, Eds., Erich R. Merz , Carl E. Walter,
Gennady M. Pshakin, Kluwer Academic Publishers, Dordrecht, 1995.

^5^ "Groundwater & soil cleanup: improving management of persistent
contaminants," National Research Council. Committee on Technologies for
Cleanup of Subsurface Contaminants in the DOE Weapons Complex: Board on
Radioactive Waste Management.; National Research Council, Commission on
Geosciences, Environment, and Resources, Washington, D.C.: National
Academy Press, 1999.

#   {#section-2 .unnumbered}

# Chemical Threats

## Terrorism Threats and Technology Needs

Potential chemical threats from terrorist attacks include chemical
weapons, toxic industrial chemicals and materials (referred to in this
report as TIMs), and explosives. Chemical warfare agents, or simply
chemical agents (i.e., nerve, choke, blister agents, etc.), are well
known and therefore possibly perceived by the general public to be the
greatest threat. However, TIMs are far more readily available and
constitute a significant threat. TIMs are defined as those chemicals
with an LCt50 value (lethal concentration for 50% of the population
multiplied by exposure time) of less than 100,000 mg-min/m^3^ in any
mammalian species and produced in quantities exceeding 30 tons per year.
[^2] Explosives, on the other hand, are undoubtedly the chemical threat
agent that has historically been most highly utilized by terrorists.

This section deals only with the challenges associated with conventional
(e.g., non-nuclear) explosives. Nuclear and radiological threats are
discussed in Section 2 of this report. Each of these specific threats
has unique characteristic and associated technology needs to facilitate
detection, preparedness, prevention, protection, and response and
recovery. This section describes these threats and associated technology
needs in more detail, gives examples of how current and previous
research within Basic Energy Sciences (BES) is helping to counter these
threats, and defines future research directions for improving homeland
defense capabilities with respect to chemical threats.

### Chemical Warfare Agents

Chemical warfare agents were designed to have devastating effects on
their target and to achieve those effects in a short period of time.
Chemical weapons are commonly grouped according to their major
physiological activity as blister, nerve, choking, and blood agents. The
nerve agent Sarin, for example, was used by the Aum Shinrikio terrorist
organization in an attack on the Tokyo subway in 1995. The attack
exposed 5,000--6,000 people to the agent, hospitalizing nearly 500
people and killing 11. Some of those requiring medical attention because
of exposure to the nerve agent were first responders and medical
personnel.

#### Detection {#detection-2 .unnumbered}

Rapid and specific detection of chemical weapons is an important
technological need. The first responders in future terrorist incidents
within the U.S. will be local law enforcement, fire, and medical
personnel, and the budgets of many localities will not accommodate
expensive detection equipment. Thus, cost restrictions are imposed on
future detectors intended for widespread use and field deployment.

The Institute of Medicine, National Research Council, published a survey
of detectors for chemical agents in 1999.[^3] Of the 100 detectors
identified, funding for their development came from the Department of
Defense (DoD) (28%), commercial companies (56%), and the remainder from
other agencies, including the Department of Energy (DOE), Environmental
Protection Agency (EPA), National Aeronautics and Space Administration
(NASA), and the Technical Support Working Group (TSWG). These figures
reflect what was previously considered to be a military need, as opposed
to a homeland defense need; however, the figures do not necessarily
reflect the source of basic research funding that led to the discovery
of fundamental principles on which these instruments are based.

All detectors surveyed had sufficient sensitivity to detect chemical
agents at high enough concentrations to present an immediate health
hazard, but only the most expensive systems had sensitivities sufficient
to ensure the complete health and safety of victims and
responders.Error: Reference source not found Further, false-positive
responses were a problem in some chemical agent detectors, which is a
highly undesirable characteristic for detectors used in a civilian
environment. The future of chemical weapons detectors relies on new
fundamental developments in the areas of separation and analysis,
materials chemistry, chemical transformations, and atomic and molecular
spectroscopy.

#### Protection/Response and Recovery {#protectionresponse-and-recovery-2 .unnumbered}

An integral part of incident response and recovery is the
decontamination of chemical agents to remove any residual source of
slowly vaporizing material. Chemical-agent simulants have been shown to
penetrate porous building materials, thereby providing a continuously
emitting source and complicating the decontamination process.[^4] An
understanding of the movement of chemical agents and decontaminating
reagents through porous building materials constitutes a technological
need for efficient and complete decontamination. This need is emphasized
by a general lack of knowledge regarding health effects from long-term
exposure to low concentrations of chemical agents. The potential for
low-level exposure also points to the need for finding biological
markers of low-level exposure to chemical agents, as well as other
chemical threats, to facilitate early detection and treatment for
exposure. Decontamination of victims and nonporous surfaces exposed to
many chemical agents can be achieved with dilute bleach and through
adsorption onto dry decontamination materials. Supporting fundamental
knowledge from BES-funded studies of chemical reactions in complex
media, materials synthesis and processing, and catalysis and chemical
transformations will guide developments in this important area.

Personal protection equipment (PPE) for chemical agents consists of
protective clothing and masks for respiratory protection. PPE suitable
for use against chemical weapons is commercially available, but the
items are bulky and physically demanding to wear. Technological needs
exist for lighter weight protective and reactive barrier materials for
PPE. Future technologies for catalytic decomposition and adsorptive
binding of chemical agents will be founded on basic research advances in
areas such as physical and chemical properties of materials, surface and
interface science, catalysis and chemical transformations, and materials
synthesis and processing.

### TIMs

In 1999, the General Accounting Office reported to Congress
(Subcommittee on National Security, Veterans Affairs and International
Relations, Committee on Government Reform, U.S. House of
Representatives) its finding from a survey conducted among law
enforcement and intelligence agencies regarding the threat of chemical
and biological terrorism in the U.S. The report concluded that "in most
cases terrorists would have to overcome significant technical and
operational challenges to successfully make and release chemical or
biological agents of sufficient quantity to kill or injure large numbers
of people without substantial assistance from a state sponsor." [^5] In
the GAO report, a "large number of people" was defined to be greater
than one thousand.

A likely alternative chemical weapon for terrorists is often considered
to be TIMs. Unlike chemical weapons, TIMs are not designed to kill
people; however, many TIMs are highly toxic and are produced in very
large quantities by chemical manufacturers throughout the world. A list
of approximately 100 TIMs and their respective toxicity ratings has been
published elsewhere.Error: Reference source not found The onset of
symptoms from TIMs exposure may be delayed for up to several days in
some cases. A powerful example of the deadly nature of some TIMs is the
accidental release of methylisocyanate in Bhopal, India, on December 2,
1984. In the Bhopal accident, 40 tons of methylisocyanate were released
over 90 minutes, exposing 200,000 people and killing 8,000. This single
incident claimed almost three times as many lives as the September 11,
2001, attacks on New York and Washington, D.C.

#### Detection {#detection-3 .unnumbered}

Many technological needs for homeland defense from terrorist attacks
utilizing TIMs are very similar to those for chemical weapons. However,
detection devices designed for use with one class of chemical threat
(i.e., chemical weapons) may not properly identify or respond to the
other (i.e., TIMs). The Department of Justice recently published the
results of a survey of 148 detectors capable of detecting chemical
weapons and TIMs.Error: Reference source not found Of 69
handheld-portable instruments surveyed, 12 had chemical weapons
detection capabilities, 52 had TIMs detection capabilities, and only 5
would respond to both chemical weapons and TIMs. None of the
vehicle-mounted, fixed-site detection systems or fixed-site analytical
or stand-off detectors had TIMs detection capability. Technological
barriers to generalized multi-threat detectors will require basic
research in separations and analysis, atomic and molecular spectroscopy,
and materials synthesis and processing.

#### Protection/Response and Recovery {#protectionresponse-and-recovery-3 .unnumbered}

Many of the decontamination and personal protective equipment issues
associated with chemical agents also apply to TIMs. However, in the case
of TIMS, material safety data sheets and first-aid information are
readily available for these industrial products. In addition, risk
assessment studies have already been performed for most common
industrial materials. Biological markers and long-term health effects of
low-level exposure are also important for TIMs.

### Explosives

As a chemical threat, explosives are dramatically different from
chemical agents and TIMs. A terrorist action utilizing a conventional
explosive may result in a catastrophic event that takes many lives, but
the event is not likely to result in post-event decontamination and
mitigation problems associated with the explosives compounds themselves.
Like TIMs, explosives are produced in large quantities throughout the
world for military and commercial applications. Some explosives can be
prepared from materials available at virtually any pharmacy. The
availability of explosives and the widespread recipes for their use in
publicly available books and on the internet contribute to the large
number of terrorist events involving explosives.

Explosives have been used in many terrorist attacks within the U.S. and
abroad. The most notable terrorist attack within the U.S. that utilized
explosives was undoubtedly the bombing of Oklahoma City's Alfred P.
Murrah Federal Building in 1995. In that event, the detonation of
several tons of ammonium nitrate fertilizer mixed with
nitromethane-based racing fuel took the lives of 168 people, including
19 children. In 1993, the World Trade Center withstood an attack by a
bomb containing in excess of 1,000 pounds of nitrourea and hydrogen gas
cylinders. Six people died and more than 1,000 people were injured in
the attack. More recently, a mixture of pentaerythritiol tetranitrate
(PETN) and triacetone triperoxide (TATP) packed into the soles of a
terrorist's shoes failed to detonate aboard an American Airlines flight
in December 2001.

#### Detection {#detection-4 .unnumbered}

Commercial detectors for explosives are deployed throughout the world to
safeguard against terrorist attacks. Lower limits of detection and
higher specificity are ever-present technological needs in the area of
explosives detection. Chemically specific standoff detection can be
especially important for safe detection of explosives. The low vapor
pressures of most explosives impose technological challenges in sample
collection and transport that are unique to the detection of this
chemical threat.

#### Protection/Response and Recovery {#protectionresponse-and-recovery-4 .unnumbered}

In some instances, the severity of a terrorist event involving an
explosive device could be mitigated by containing the primary blast or
through shielding from the blast. The fundamental technological barriers
involved in containing a blast are embodied in materials science and
structural engineering. Fundamental advances in the areas of separations
and analysis, atomic and molecular spectroscopy, and surface and
interface science will lead to better detectors, sampling methodologies,
and incident containment technologies in the future.

## BES Research Accomplishments and Implications for Countering Terrorism

Fundamental research within the DOE's Office of Basic Energy Sciences
has contributed significantly to existing and emerging technologies that
can be applied to countering terrorist chemical threats. Fundamental
research will continue to have an impact on all areas of homeland
defense, including detection, preparedness, prevention, protection, and
response and recovery. Examples of some of this research are outlined
below.

### Detection 

#### Optical Spectroscopy {#optical-spectroscopy .unnumbered}

Interfering background components are a ubiquitous barrier to real-world
deployment of sensors and detectors. BES-supported research programs in
separations and analysis are assisting in breaking down these barriers
and enhancing the ability to confidently detect trace compounds. Several
research programs are devoted to the development and utilization of
laser-based ultra-sensitive detection schemes for monitoring molecular
species. Fluorescence, absorption, and laser/mass spectrometric
techniques are employed to push the detection limits toward the ultimate
goal of single molecule detection. Research in advanced laser-based
chemical measurement problems has led to advances in high-sensitivity
and high-resolution measurements in gas and condensed-phase chemical
systems. This research has evolved to investigate molecules in micro-
and nano-domains and at interfaces, including molecules adsorbed on
individual particles, contained in microdroplets, and within
microfluidic "lab-on-a-chip" devices.

Specialized light sources at BES Scientific User Facilities provide
researchers with the ability to scan the electromagnetic spectrum from
x-rays up to the infrared. These powerful light sources provide a tool
for gaining fundamental insight into molecular spectroscopy and
properties that may form the basis for future detection techniques.
Resonant laser photoionization of sputtered atoms from surfaces can
measure as few as 10 atoms and can measure target analytes in
concentrations as low as parts per trillion. Fundamental laser-based
studies, coupled with advances in microfabricated separation and
analysis systems such as lab-on-a-chip devices, hold much promise for
future technologies to counter terrorism. BES-supported fundamental
studies in energy transfer and optical spectroscopy have led to the
discovery of detectors for nitroaromatic explosives and structurally
related compounds at the ppb level.

Microfluidics for Chip-Based Detection

Many of the detection and identification approaches for countering
terrorism will benefit from microfabricated chemical and biochemical
measurement devices. To meet these needs, lab-on-a-chip technology must
be able to identify chemical and biological materials in liquids with
low false signatures. In these devices, typical analysis volumes will be
in the range of one nanoliter where a concentration of one femtomolar
would represent only one to several molecules for
analysis.![](media/image7.jpeg){width="2.2875in"
height="3.2395833333333335in"}

Measurement at the single molecule limit discussed above requires
fundamental under-standing of the transfer of target species through the
measurement system. Investigations supported by BES have advanced our
understanding of the requirements for low-level (single molecule)
detection in the liquid phase. Statistical principles developed and
experimentally confirmed in these studies allow molecular detection
efficiencies to be estimated for a given experimental condition.

*\[Oak Ridge National Laboratories\]*

Photochemical Nanomaterials for Explosives Detection

Rapid detection of chemical, biological, or explosives threats has
emerged as a major need in countering terrorism. In this area,
low-power, portable, and inexpensive devices are key to widespread
deployment. BES-funded research on the photochemistry of materials has
focused on understanding photosynthesis. In photosynthesis, a large
assembly of molecules in a green plant each collects a photon of light,
and the energy is then funneled into a small spot, where the chemical
conversion of carbon dioxide into fuel can occur. The concept of
building an antenna to harvest energy over a large area can also be used
to amplify the detection of chemicals. Studies of luminescent silicon
nanoparticles, sponsored by DOE BES, led to the development of quantum
dots and nanowires of silicon that collect light over a large area and
then funnel the energy to the vicinity of a molecule of an explosive,
which amplifies the optical signature of the target molecule. Similar
light harvesting/amplification detection concepts are being developed in
other university laboratories and in private industry.

*\[University of California, San Diego\]*

![](media/image8.jpeg){width="3.4972222222222222in"
height="3.3319444444444444in"}

**A fingerprint from a person who had recently handled TNT shows**

**up as a dark spot on a subway ticket after treatment with the
imaging**

**agent (right ticket).**

Mass Spectrometry for Airport Screening

Mass spectrometry has proven to be one of the more effective tools for
the rapid trace detection of threat compounds, such as explosives, toxic
chemicals, and biological materials. BES-funded research has led to the
development of quadrupole ion trap mass spectroscopy, many features of
which are incorporated in commercial ion trap instruments that may be
found at airport screening stations. Ion traps greatly improve our
ability to miniaturize high-performance MS. These basic research
developments are also incorporated into the U.S. Army Soldier and
Biological Chemical Command that is developing the Block II Chemical
Biological Mass Spectrometer (CBMS). This program is developing,
demonstrating, and delivering to the Army the first integrated
instrument capable of real-time detection and identification of both
chemical and biological warfare agents on the battlefield.

*\[Oak Ridge National Laboratory\]*

![](media/image9.jpeg){width="3.172222222222222in"
height="4.229861111111111in"}

Nanocomposite Materials for Chemical Sensing

![](media/image10.png){width="1.7811023622047244in"
height="2.3751968503937007in"}

An important class of chemical sensors is based on metal/polymer
composites materials whose ability to conduct electricity changes in a
dramatic fashion when exposed to target chemicals. The secret of this
behavior is in controlling the spacing between the electrically
conductive metal particles. As chemicals are absorbed, the polymer
expands, creating more space between the particles and making it harder
for electrons to pass from one particle to the next. While extremely
sensitive, the practical application of these sensors is limited by
previous ability to build composites with precise and uniform spacing
between the metal particles.

BES supported research has led to a new approach for building extremely
uniform and controlled composite structures. These composites are
members of a new class of Field-Structured Composites.^1^ They consist
of 1--5 micron sized magnetic metallic particles suspended in an uncured
polymer solution. The suspension is then exposed to an axial magnetic
field, causing the magnetic particles to form chains with highly uniform
particle spacing. Upon final curing, these composites demonstrate high
sensitivity and extremely reproducible sensing performance.\
*\[Sandia National Laboratories\]*

^1^ J. E. Martin, R. C. Hughes, and R. A. Anderson, *Science*, Dec. 21
news brief.

#### Magnetic Resonance Imaging and Spectroscopy {#magnetic-resonance-imaging-and-spectroscopy .unnumbered}

The emerging technique of Magnetic Resonance Force Microscopy (MRFM) is
being utilized to study problems where high-resolution 3D imaging is
important. Scientists are combining the resolution of atomic force
microscopy and the imaging capabilities of magnetic resonance to produce
a new method of nondestructive and chemical-specific analysis. Ex situ
magnetic resonance imaging is a fundamental breakthrough that may
provide a future detection technology. Nuclear magnetic resonance, which
places the sample "outside" the magnet, has potential for detecting bulk
quantities of enclosed materials.

#### Mass Spectrometry {#mass-spectrometry .unnumbered}

The specificity required by many analytical problems benefits from the
high information content of mass spectral analysis. Fundamental research
has led to many advances in our understanding of the chemical processes
comprising the framework of mass spectrometry, ion formation,
manipulation, and detection and exploiting its multidimensional
capabilities for chemical analysis and characterization.
Electron-transfer chemistry, correlation of gas- and condensed-phase
chemistry, ion-molecule and ion-ion chemistry, surface chemistry, and
mechanisms and energetics of ion processes are among the wide array
fundamental issues addressed in this research. Many of the advances from
these studies aid in enhanced analysis capabilities and for the future
miniaturization of mass spectrometers for field detection devices and
have already demonstrated capabilities for detection of chemical agents
and explosives. Precise methods have also been developed for analyzing
the distribution of stable light isotopes (e.g., D/H, ^13^C/^12^C, and
^18^O/^16^O) to better than 1 part in 10^5^ for samples with masses less
than one nanogram. Precise isotopic ratio measurement may play a
significant role in future forensic and attribution efforts to counter
terrorism by helping to identify the geographical and manufacturing
origin of terrorist tools.

#### Detection and Nanoscale Properties of Materials {#detection-and-nanoscale-properties-of-materials .unnumbered}

The future of detectors for countering chemical threats from terrorists
lies in making the devices smaller and more robust. Fundamental studies
in materials synthesis and processing are providing the groundwork for
future developments in this area. Research into the use of templated
self-assembly to create nanoporous inorganic materials may find

Nanomaterials for Integrated Chemical Analysis

Detection of low levels of chemical toxins with high reliability (low
false response) is a major challenge to sensor technologies for
countering terrorism. An alternative approach to improved detection
sensitivity and selectivity can be realized by integrating chemical
preconcentration, chemical separations, and detection into a single
miniaturized total chemical analysis system. This approach relies on
multiple levels of discrimination to achieve high sensitivity and low
false responses.

BES-supported research has made critical contributions to the
development of hand-held chemical and biological detection systems. In
the example, self-assembled mesoporous sol-gel materials provide highly
controlled nano-sized pores for preconcentration of chemical toxins.
BES-supported research on thin film deposition processes has allowed
direct integration these chemically selective films resulting in greater
than one-hundred fold improvement in the miniaturized system analysis
sensitivity. The improved sensitivity is critical to the overall
capability for the integrated system that is now being evaluated for
protection of public assets from terrorist attacks on U.S. soil.

![](media/image11.wmf){width="2.1354166666666665in"
height="1.6055555555555556in"}

The micro-scale heater with its integrated nanoporous film is used in
the Sandia National Laboratories developed µChemLab to provide a
100-fold boost to the performance of this hand-held total analysis
system.^1^

^1^ W. A. Groves, E. T. Zellers, G. C. Frye, ***Analytica Chimica
Acta,*** 37 (1998), 131-143.

applications in future development of sensor platforms and separations
elements. The basic principles governing self-assembly of complex hybrid
interfacial and laminar species are also being addressed in parallel
efforts. Novel ceramic/polymer and metal/polymer nanocomposites,
prepared by employing magnetic fields, represent new classes of tailored
materials with a variety of potential applications in chemical sensing.
The fundamentals of thin film growth, epitaxy, and structural evolution
are also being studied with a focus on elastic strain resulting from
film microstructure and surface morphology. Materials containing d- and
f-electrons can exhibit complex and collective states resulting from
competing interactions. Research has shown that these complex states are
highly susceptible to small perturbations and may form the basis for
future detectors of weak magnetic fields, small temperature or volume
changes, and chemical environment and incident electromagnetic
radiation. The results of these studies provide important support for
future development of field sensors for chemical threats.

The role of nanostructures in controlling the behavior of materials is
being elucidated through fundamental research. Theoretical and
experimental tools are being utilized to understand the fundamental
mechanisms governing the electronic and optical properties of
nanostructured materials. The basic understanding gained from these
studies will lead to the discovery of new material properties and
physics architectures that can be utilized for improved efficiency and
sensitivity in electronic and optical detector systems. In related
research, advances in our fundamental understanding of the atomic and
nanostructural processes governing materials properties are being sought
through the study of energetic-particle synthesis, modification, and
analysis. The physics and deformations of ultrafine scale composites
that exhibit extremely high specific strength levels and that can be
assembled into nanostructures capable of responding to their environment
are also being investigated.

The role of surfaces and interfaces in the development of new materials
for detecting chemical threats is being elucidated through fundamental
studies at several national laboratories and universities. The
atomic-scale kinetic processes of diffusion and atom-defect
interactions, as well as collective phenomena such as self-assembly, on
solid surfaces are being studied. Self-assembly of metals and
semiconductor materials is a promising approach to rapidly producing
nanoscale sensor arrays and quantum dot networks that may be employed in
future chemical threat detection devices. An atomistic understanding of
the chemical and physical interactions that control solid/solid and
solid/liquid interface formation is important for developing predictive
models of adhesive bond strength, interfacial stability, and flow
kinetics. Understanding these phenomena will assist in tailoring
material surfaces for use in sensing applications. Surface phenomena in
thin films are likely to be the basis of microelectromechanical sensors
of the future. Studies of surface acoustic waves (Raleigh waves) in thin
films can serve as the basis for future developments in this important
area. Modification of Raleigh wave velocity resulting from surface
modification may be used to detect airborne chemical agents.

Finally, detectors of chemical threats will continue to get smaller and
less expensive through the advances in the area of microfabrication.
Research has led to the development of high-throughput x-ray
microtomography, capable of providing full reconstructions of
micron-size parts, and high-resolution 3D imaging. Advances in
lithography, electroforming, and molding (LIGA) research is providing
the fundamental knowledge required to produce many of the micron-sized
parts that will be required in detectors of the future.

### Preparedness

An important aspect of countering terrorism is maintaining a state of
preparedness. Remaining prepared may require that detection devices be
deployed with an onboard power source. When an event occurs, devices
need to operate reliably, without a power-source failure. Maximizing the
power and lifetime of batteries is important to maintaining a state of
preparedness. Fundamental research into the synthesis and properties of
materials for thin film rechargeable lithium batteries has examined the
physical vapor deposition and properties of electrochemically active
thin film materials between 50 nm and 5 microns thick. The resulting
batteries are very thin, less than 15 microns, and exceptionally stable,
and they provide both a long cycle life and a long shelf life in the
charged state. Design changes required to achieve the optimal low cost
and environmentally benign rechargeable lithium batteries are being
addressed. The high costs and environmental unacceptability of cobalt
containing electrodes is an important issue addressed in this research.
The formation and control of interfacial films that form on the
electrode surfaces as a result of chemical reactions between the
electrodes and electrolytes are also being addressed, along with
overcharge and overdischarge problems, and mass transport at electrodes.

### Prevention

Preventing terrorist attacks is the ultimate goal of many agencies and
the focus of much fundamental and applied research. Basic research into
amorphous and aperiodic materials is being conducted with the goal of
understanding the effects of initial atomic arrangements on
devitrification and deformation behavior. The influence of crystal
chemistry on the structural stability of aperiodic systems and atomic
mobility in these systems plays key roles in determining the physical
properties of the materials. This research is laying the groundwork for
the development of improved heat-resistant materials, longer-lived
insulators, and ultra-hard materials. Such materials would potentially
be harder to breach, harder to damage, and even less susceptible to
fire.

### Protection

If a terrorist event occurs, the first responders are typically local
emergency personnel. Fundamental research may result in materials that
better protect first responders. Investigations into the fabrication of
carbon nanotube membranes may lead to new adsorbent barriers. Membranes
consisting of well-defined arrays of small, aligned graphitic pores are
being sought to separate energy-related molecules such as hydrogen,
methane, carbon monoxide, and carbon dioxide. Extending the results from
this work to the adsorption of larger molecules used as chemical threats
may contribute significantly to the personal protective equipment of the
future. In related research, mesoporous materials containing
mesostructures characterized by a precise periodic arrangement of
inorganic and organic constituents on the 1--50 nm scale can be prepared
by evaporation-driven self-assembly. Scientists have shown that the pore
size can be controlled in thin films prepared by the process. The
synthetic method holds potential for the preparation of new materials
with membrane/filtration applications.

Adsorption, absorption, filtration, and separation are processes that
can potentially remove selectively targeted chemical agents from the
environment. A unique high-pressure adsorption process has been
discovered in fully hydrated zeolites. Superhydrated nanoporous
materials can retain an excess of water after pressure release, thus
permitting selective adsorption, immobilization, and storage of chemical
species. At high pressures, the pores of zeolites expand because of the
excess of water, allowing larger cations to enter the nanopores. After
the pressure release, the pores contract and trap cations. Superhydrated
zeolites and nanoporous materials can find application in waste
remediation and immobilization (separation) of chemical and biological
material.

Fundamental catalysis studies are examining the reactivity of Au/TiO~2~
catalyst. A unique activity of this system for destruction of SO~2~ has
been discovered for catalysts of Au/TiO2, and related gold/oxide
catalysts may find utility in the destruction of sulfur mustard chemical
agents. Research has shown that chemical species adsorbed onto the
surface of oxides, such as silica, alumina, and zirconia, undergo
radiolytic processes more efficiently. A combination of sonication and
radiolysis enhances the efficiency of remediation even more. Sensitized
large-gap semiconducting nanocrystals (ZnO, porous Si) are being used to
detect the presence of chemical vapors. Frontier research supported by
BES in surface-supported polymerization and supported-polymer phase
formation holds promise for future advances in lightweight protective
clothing.

### Response and Recovery

In open environments, even semi-volatile chemical agents and TIMs will
dissipate. Nonporous surfaces are readily decontaminated with existing
products. However, when semi-volatile chemicals diffuse into porous
building materials, they become much more difficult to decontaminate,
and they can form slowly emitting sources of low-level concentrations of
agent. Research into the fundamental aspects of advanced oxidation
processes may play a significant role in the development of future
decontamination strategies for porous materials.

Photo- and ionizing-radiation induced effects at nonocrystalline oxide
materials are being investigated. Photolytically and radiolytically
formed species in heterogeneous system may degrade, neutralize, and
destroy toxins, chemical agents, and TIMs. By chemical modification of
the oxide surface a selective adsorption and destruction of reactants
may be achieved.

## Scientific Issues and Research Opportunities

The scientific issues associated with countering chemical threats of
terrorism are discussed below in terms of the major emphasis areas of
homeland defense. The fundamental issues and the research opportunities
in the areas of detection, preparedness, prevention, protection, and
response and recovery fall into the BES funding areas of materials
synthesis and processing, physical and chemical properties of materials,
surfaces interfaces and thin films, microfabrication, catalysis and
chemical transformations, separations and analysis, and atomic and
molecular spectroscopy.

### Detection

  ----------------------------------- -----------------------------------
  **Technology Need**                 **Present Problem**

  Devices to enable chemical threat   Sensors and detection systems must
  detection are required for both     become smaller and less expensive
  "detect to treat" and "detect to    to be available for *all* first
  protect" scenarios.                 responders and for deployment in
                                      surveillance arrays.
  ----------------------------------- -----------------------------------

Micro- and nano-fabricated devices that combine separation and detection
elements into an integrated device (lab-on-a-chip) are an emerging
technology that will play a significant future role in countering
terrorism. There is a need for sensors that respond selectively to a
given analyte, as well as those that recognize and respond to a broader
set of threat chemicals and/or harsh conditions that pose a health
hazard. Advances in materials chemistry, such as the development of
selective coatings, are needed before molecule-specific recognition
elements for sensors can be realized. High information content
analytical methods, such as mass spectrometry, provide means of
minimizing false positives while being sufficiently sensitive to achieve
zero false negatives. Fundamental advances are required to make these
methods fieldable and to expand their utility. Sample collection and
transport requirements will necessarily change as detection technology
morphs to meet the challenges of the future. The technological frontiers
associated with each of these challenges are discussed here.

#### Microfluidics {#microfluidics .unnumbered}

Although some microfabricated lab-on-a-chip technologies have already
moved from the laboratory to the market, fundamental research topics
remain to be addressed. In particular, fundamental understanding of
electrokinetic transport is not well developed. The structure of the
electrical double layer formed at the solid/liquid interface has still
not been directly probed experimentally even though its existence was
articulated long ago. Nonintrusive probes must be developed with
nanometer spatial resolution for such studies. Additional fluid pumping
mechanisms must also be developed to allow compact low-power devices to
be realized.

As the lateral dimensions of microfluidic channels shrink, the
surface-to-volume ratio increases, as do the demands on our ability to
pacify surfaces to preclude nonspecific adsorption of liquid-borne
materials. Surface characterization tools and improved micron-scale
surface modification and patterning chemistries are needed to allow
viable manufacture of lab-on-a-chip devices with spatially heterogeneous
surface chemistry. These chemistries will also find utility in improving
microfabricated gas phase separation and analysis devices.

New quantification tools are also needed for microfluidic devices.
Typical analysis volumes in lab-on-a-chip devices are in the
one-nanoliter range. Femtomolar concentrations in such volumes imply low
numbers of molecules in the analysis volume. Measurement tools with
extreme sensitivity are needed, and ideally, they should also be
miniature in size and compatible with microfabrication procedures.

***Nanofluidics***

The transport of fluids through nanoscopic conduits is an area of study
that has received very little attention, although it is fundamental to
life. The fabrication of such conduits and the active transport of fluid
through them are referred to as nanofluidics. Detailed understanding of
nanofluidic transport will likely lead to revolutionary technological
capabilities (e.g., the ability to sequence *single* molecules of DNA at
rates many orders of magnitude faster than currently possible).
Understanding of molecular transport in nanoscopic domains will require
probing many fundamental questions in the fields of fluid dynamics and
statistical physics. Theories that need to be investigated under
nanoscale confinement include one- and two-dimensional fluid theories,
fundamental assumptions of fluid dynamics such as \"stick\" or \"slip\"
boundary conditions, the scaling of polymer structure and dynamics with
chain length, and the validity of continuum theories.

Fabrication tools must be developed to realize nanofluidic devices.
Although multiple strategies for formation of nanochannels appear
feasible, fundamental questions regarding intrinsic surface roughness
associated with each fabrication strategy will be important.
Molecular-scale channels are essentially entirely interfaced with no
bulk fluid; thus, understanding and control of interfacial chemistry on
the nanometer scale are paramount. Molecular dynamics simulation tools
will be needed to understand transport at this scale, and an
understanding of the validity of continuum theories at nanometer scale
must be established. Importantly, transport through molecular-scale
conduits implies that quantification tools must be effective at the
single molecule limit. Optical and electrochemical techniques must be
developed to interrogate single molecule transport.

Chemical Sensors

  ----------------------------------- -----------------------------------
  **Technology Need**                 **Present Problem**

  Highly selective sensors are needed Easy-to-use chemical sensing
  to identify target chemicals in     techniques are not capable of
  complex backgrounds.                molecule specific recognition.
  ----------------------------------- -----------------------------------

The current trend in portable chemical detection is to make sensors
selective to the extent of giving analyte discrimination at the
molecular level. Detection with molecular specificity is a difficult
challenge, and as the number of compounds posing chemical threats
continues to increase, the problem only becomes increasingly difficult.
Within the context of terrorist chemical threats, it is useful to
consider a second paradigm---that of detecting chemical properties or
environmental conditions presenting an immediate health hazard. For
example, a large number of materials will hydrolyze to produce highly
acidic environments that generate a health hazard. It may not be
feasible to detect all these chemicals with molecular specificity;
however, it is feasible to detect acidic environments. Potential targets
for generalized detection schemes include molecules that bind to iron
competitively with oxygen, and molecules that mimic acetylcholine. It
may be useful to think of detectors for these chemical threat groups as
"effects sensors," with the emphasis on the effect, rather than on the
specific chemical. Fundamental research to overcome the challenges of
developing "effects sensors" should be pursued as a worthwhile target,
even though the challenge may not be as great as that of
molecule-selective sensor development.

Molecule-selective chemical sensors for standalone application, as well
as those embedded into integrated systems discussed above, will play a
crucial role in countering threats of terrorism. At the core of a
threat-specific sensor is a molecular recognition event coupled to a
transducer to produce a detectable signal. Many sensors employ a thin
sorbent layer of chemically selective material to collect and
concentrate analyte at the interface of the coating and transducer.
Detection is elicited by some change in the physiochemical properties of
the interface. There are a number of transducer platforms for coupling
the binding event to some observable signal. Designing the coating for
specific analytes so as to maximize the collection of analyte and to
minimize the collection of interferents is the most significant
challenge to produce an effective chemical sensor.

Chemical sensors can employ biological entities such as antibodies,
enzymes, receptors, or whole cells as recognition elements, commonly
referred to as biosensors. With the advent of recombinant antibodies and
phage display antibody libraries, recognition elements can now be found
even for analytes for which a natural receptor does not exist. However,
biological receptors have rather limited chemical and physical stability
that can restrict their use under harsh conditions that include high
temperatures, extremes in pH, or nonaqueous media. Biomimetic receptors
are attractive alternatives for these applications, since they lend
themselves to rational design and chemical synthesis. In some cases,
affinities and specificities that rival natural receptors have been
achieved. The most successful examples of this type have been for
inorganic ions as analytes. However, with targets of increasing
complexity, this strategy becomes less tenable because of the synthetic
challenges associated with the receptors.

New chemically selective materials are needed that can recognize complex
analytes. A further requirement is that the synthesis and processing of
these materials be readily incorporated into transducer platforms for
use as sensors. It would also be desirable that the processes to produce
these materials be amenable to existing microfabrication technologies.
Strategies such as molecular imprinting offer considerable potential for
making important contributions to this area. Molecularly imprinted
polymers (MIPs) are robust network materials that may be tailored for
specific analytes. They offer an advantage in that they can function
under harsh conditions. Not surprisingly, there has been considerable
effort in recent years to employ MIPs as the recognition element of
chemical sensors. Basic research is needed to expand the range of
targets (ligands) for which this technique can be used. Important
ligands include water soluble biologicals such as peptides and proteins.
Imprinted polymers are produced by bulk polymerization and, as such, are
not conveniently coupled to transducer platforms. Important developments
would include new imprinting formulations and processes that are
amenable to thin film formation. The ability to produce selective
materials that can be produced in 2D or 3D spatially resolved domains by
photolithographic processes would facilitate their incorporation into
devices. There is also a lack of basic understanding of how recognition
sites of MIPs are produced. An understanding of this process can lead to
improvements in selectivity and in convergence towards producing more
uniform \"monoclonal\" recognition sites.

An additional approach to producing recognition elements for chemical
sensors is through organic polymer nanophases grafted-from sensor
platforms by surface initiated polymerization (SIP). SIP is a new and
powerful method for tethering ultrathin (10--100 nm) polymer layers onto
surfaces. SIP offers potential advantages over attaching preformed
polymers to the surface because, for example, it is easier to achieve
high grafting densities. However, most of the efforts devoted to SIP
have employed standard free radical initiators, resulting in polymers
with broad molecular weight distributions and limited control over
polymer architecture. Only recently have methods like living radical and
living ionic polymerization been used to gain better control over the
SIP process. Using these methods, diblock, triblock, and other
architectures could be grown from the surface, and chain end
functionalization could be achieved. Block copolymer composition can be
used to control nanophase formation in tethered polymer brush systems.
While experimental work in this area is in its infancy, theory and
simulation predict that a rich range of patterned films could be
achieved by controlling block copolymer composition, architecture,
grafting density, and environment. Systematic studies to synthesize
well-defined block copolymer brushes by living SIP processes and to
investigate their properties are needed.

Control over the spatial extent of polymerization is a critical issue
for incorporating functional polymers into micro- and nano-fabricated
devices by both MIPs and SIP polymer formation. The small scales of
modern MEMS devices provide an additional barrier to producing polymeric
recognition elements. The chemistries discussed above must be performed
on platforms and within the confines of micro- and nano-channels with
dimensions less than that of a human hair. The prospect of producing
chemically distinct domains within these limited real-estate devices is
particularly challenging. Multiple domains within a single device are
one strategy for expanding system functionality.

One of the "holy grails" of trace explosives detection is the quest for
detectors so sensitive that detection of low vapor pressure explosives
becomes realistic. While some volatile explosives (e.g., nitroglycerin)
typically have vapor pressures in the parts per million (ppm) range or
higher, explosives such as RDX and PETN have vapor pressures in the low
parts per trillion (ppt) range. When these compounds are incorporated
into plastic explosives such as C-4, semtex, and detasheet, the vapor
pressures are reduced further by matrix effects, and of course, any
packaging or concealment of the explosive will further reduce the amount
of vapor available for collection and analysis. As a result, actual
vapor pressures in the field may be in the parts per quadrillion range
or even lower. Basic research in interface and surface science,
separations and analysis, and materials synthesis and processing are
needed to produce the breakthrough advances required to enhance the
sensitivity of existing detectors or to develop a completely new sensor
with superior sensitivity. Incremental improvement in sensitivity will
lead to improved vapor detection of explosives with intermediate
volatilities (e.g., TNT).

#### Mass Spectrometry {#mass-spectrometry-1 .unnumbered}

High information content analytical methods, such as mass spectrometry,
can obviate the selectivity problems that are so troublesome for
MEMS-based sensors. Mass spectrometry has inherent sensitivity but is
hampered by efficiency in ionization and ion detection. Tandem mass
spectrometry techniques can detect targeted compounds with high
confidence, but this technique is limited to analyzing one target
molecule at a time. While a computer can step through the detection of
up to about 50 analytes sequentially, new techniques to permit the
detection of many targets without reducing the detection duty cycle will
be needed to meet the requirements of TIMs detection.

Bringing the high information content and sensitivity of mass
spectrometers into a size and price range that makes them widely
available to first responders and as continuous monitors of air and
water sources will require overcoming some fundamental barriers.
Reducing the size of mass analyzers requires studies that investigate
the effects of Coulomb forces on ion manipulation and analysis.
Microfabricated gas phase micro-instrumentation is a rapidly emerging
area of science. The development of truly miniature mass spectrometers
that can be hand held could have a huge impact on our ability to monitor
the air for harmful materials. Understanding of ion chemistry and
physics in confined spaces must be developed. Small lateral dimensions
for gas phase devices also implies increased interaction with container
walls. Small mass spectrometers may also allow operation at relatively
small mean free path conditions (high pressure), and new quantification
tools for ions may be needed.

There is also a need for advances in laboratory-based approaches to
separations and analysis. The recent anthrax terrorist attack on the
U.S. has shown how quickly our analytical laboratory capacity can become
overwhelmed. New methods of applying high information content analytical
methodologies will provide faster sample throughput and improve the
accuracy of analysis.

  ----------------------------------- -----------------------------------
  **Technology Need**                 **Present Problem**

  Chemical signatures must be         Develop versatile collection
  extracted from gas, liquid, and     approaches that couple well with
  solid sources.                      miniaturized sensor systems.
  ----------------------------------- -----------------------------------

One of the principal basic research areas related to chemical detection
is the development of adsorptive materials for the collection of
chemical agents, TIMs, and explosives. A common sampling application
involves adsorption of gas phase species from air, but adsorption of
molecules from other media such as water is also important. Selective
adsorption from air by molecular recognition processes represents a
fundamental research problem with the potential for enhancing detection
levels and reducing background interference.

#### Sample Collection and Transport {#sample-collection-and-transport .unnumbered}

Fundamental research in polymer films and molecular recognition that
will lead to advances in selective sensing elements is directly relevant
to selective sampling. In addition to SIP and MIP soft materials,
several other materials offer promise in this area, including sol-gels,
carbon-based materials such as carbon foams or carbon-nanotubes, and
composite materials. Several properties are needed for a material to be
a good adsorbent for chemical agents, TIMs, or explosives. The material
needs to have a high adsorption efficiency for the molecules of
interest-----as close to 100% as possible. For low volatility species
such as some explosives, it may be relatively easy to find such a
material, but the problem becomes more difficult as the volatility of
the species to be trapped increases. The adsorptive material should also
have a high surface area, which combined with efficient adsorption would
result in a high adsorptive capacity for the analytes of interest. For
reactive chemical agents and explosives, it is also necessary for the
adsorptive material to release the analyte collected to a detector with
minimal decomposition. One common means of releasing the analyte from
the adsorbent is via surface heating, and with some current
adsorbent/analyte pairs, this can lead to significant sample loss
through decomposition. For use in real-world settings, the adsorbent
ought to be robust, difficult to poison, and easily regenerable if
degradation over time is a problem. Future research in materials
synthesis and processing and separations and analysis will provide
enhancements for chemical threat detection devices of the future.

Sample transport is another key issue associated with sampling of
chemical agents and explosives. This is most likely to be important with
low vapor pressure species, where detection in air will rely upon either
very low amounts of vapor or airborne particles. Both experimental and
modeling studies of particle dispersion and transport in air can be
useful in addressing these issues. Such studies can, for example, help
to establish how much sample is available in air under different
environmental conditions, when a low vapor pressure dictates the need to
detect particulate matter. Several sampling issues are more likely to
arise during the detection of explosives rather than chemical agents.
These issues are mainly related to the lower vapor pressures of many
explosives, so they may also arise in the detection of some chemical
agents with relatively low volatilities. When relying on particles to
perform trace chemical detection, it will often be necessary to dislodge
particles from various surfaces as a first step in sample collection.
Low vapor pressure explosives are so adsorptive that they will adhere to
almost any surface at room temperature.

Development of a material that shows little adsorption of these
compounds at room temperature could enhance detection systems by
reducing adsorptive losses on ductwork and other surfaces during
transport. Dislodging material for sampling can employ either direct
physical contact (swiping) or air flow methods (e.g., air jets). In
either case, optimization of the sampling procedure can be critical.
While this area is somewhat applied, there are fundamental aspects of
particle physics, surface and interface science, and fundamental
interactions that are at the heart of particle sampling under realistic
conditions.

  ----------------------------------- -----------------------------------
  **Technology Need**                 **Present Problem**

  Standoff detection of chemical      Improvements in range, portability,
  toxins.                             and sensitivity are required.
  ----------------------------------- -----------------------------------

In addition to the technological needs in support of new sensors
discussed above, advances in stand-off detection methods for field use
are necessary for countering future chemical threats. In stand-off
detection, the sample is not physically transferred to the detection
device, as required for the sensing and analytical methods discussed
above. Instead it is interrogated from some distance based on a physical
or spectral property of the material.

#### Atomic and Molecular Spectroscopy {#atomic-and-molecular-spectroscopy .unnumbered}

Remote laser induced fluorescence (LIF) sensing has been widely used for
atmospheric monitoring, especially for the detection of small molecules
such as OH, NO~2~, and SO~2~. An interesting modification to the LIF
method is to perform laser-induced photodissociation on the species of
interest and then measure LIF of a sensitive fragment molecule. This
photofragmentation LIF approach has been used to detect
2,4,6-trinitrotoluene (TNT) vapor in air with a limit of detection of 8
ppb.[^6] Detection of fluorescence from photodissociated NO makes this
method somewhat selective; however, the bulk of the equipment required
and the associated laser hazards currently make this technique
impractical for hand-held field use.

Laser induced breakdown spectroscopy (LIBS) is another laser-based
method beginning to be used for the characterization of many solid
materials, including single particles. LIBS is an atomic emission
spectroscopy technique that uses a laser-induced microplasma,
functioning as both the sample volume and the excitation source. The
laser-induced breakdown itself can be defined as the generation of a
near totally ionized gas (i.e., plasma) by the end of the initiating
laser pulse. Advances in laser technology are required to bring these
analytical methods out of the laboratory. Vibrational spectroscopy has
found practical use as a stand-off detection method. Laser induced Raman
(LIR) spectroscopy is a highly informative technique for molecule
detection. Excellent selectivity has already been demonstrated for many
of the substances of interest to homeland security. While it is less
sensitive than LIF or LIBS, it is clearly useful as a remote probe for
the detection of what are essentially pure substances. It also has the
inherent advantage, shared with LIF, of having the potential to probe
large areas of sample, using powerful expanded lasers and highly
selective imaging detectors, although this is incompatible with easily
transportable hand-held systems.

No single laser-based spectroscopic technique can be expected to detect
the wide range of chemical compounds with the necessary sensitivity and
selectivity. However, each method has important merits, and some
combination of these methods could form the basis for a powerful and
highly useful routine monitoring instrument. Fundamental issues that
remain to be addressed include a lack of basic spectroscopic data (LIBS,
LIF, and LRS) for some species, improvement in overall sensitivity for
all methods, and sampling statistics (especially for LIBS).
High-throughput applications may require new imaging detection systems
with improved sensitivity.

### Prevention

  ----------------------------------- -----------------------------------
  **Technology Need**                 **Present Problem**

  Widespread use of TIMs in industry  Minimize or eliminate inventories
  creates targets for terrorists.     of TIMs by developing alternative
                                      chemistries and processes to reduce
                                      TIMs inventories.
  ----------------------------------- -----------------------------------

Many of the opportunities for preventing future acts of terrorism with
chemical threats involve limiting access to materials through
institutional controls. However, opportunities exist for fundamental
research to assist in countering terrorism through the development of
new chemical processes that assist in reducing inventories and access to
highly toxic industrial materials. Industrial processing centers that
use large quantities of TIMs are significant targets of opportunity for
terrorist attacks because of the potential release of these dangerous
materials and their impact on the public. Significant opportunities
exist to develop new chemistries that minimize or eliminate the use of
TIMs and to reduce inventories of these materials. For example, since
the accidental release in Bhopal, many chemical manufacturers have found
ways to make pesticides either without using or without storing large
amounts of methyl isocyanide. Development of alternative synthetic
chemistries, new robust catalysts, and production and processing systems
that minimize the use of hazardous materials significantly reduce the
threat to the public from terrorist actions. An example would be the
development of robust solid acid catalysts to eliminate the use of
liquid HF in petroleum processing.

### Protection, Response, and Recovery

  ----------------------------------- -----------------------------------
  **Technology Need**                 **Present Problem**

  Personal protective equipment and   Current barrier materials are
  barrier materials require further   cumbersome to use.
  development.                        

  Advances in filtration technologies Knowledge must be developed to
  are needed.                         design better, more efficient,
                                      stable, and selective catalysts for
                                      chemical threat destruction with no
                                      toxic byproducts

  Lighter weight protective clothing  Fundamental research at the
  is required.                        forefront of materials chemistry
                                      must be developed.
  ----------------------------------- -----------------------------------

Personal protective equipment to guard against the effects of chemical
agents and TIMs has existed for many years, yet there are many
opportunities for fundamental research to provide a basis for improved
systems. Technological barriers impede the development of catalytic
materials that operate under ambient conditions to decompose chemical
agents and TIMs. Catalysis research sponsored by BES can address these
issues. Materials synthesis and processing advances hold promise for
developing lightweight barrier materials for comfortable protective
clothing. The porous nature of common building materials coupled with
uncertainties about the lifetime of chemical agents in environmental
settings presents technological challenges to decontamination in a
post-event recovery after a chemical attack. These issues, along with
the need for stronger barrier materials, present a set of technological
challenges for future protection, response, and recovery aspects of
homeland defense.

Current filtration technologies remove nerve agents by adsorption,
whereas more volatile reagents (e.g., blood, choke, and blister agents)
are removed through a combined process of catalytic decomposition and
adsorption. Advances in filtration technology will leverage a
significant BES investment in catalysis and chemical transformations.
Adsorption of reactive chemical agents and TIMs onto different
substrates is insufficiently understood. Data for adsorption on metal
oxides, surfaces of plastics, fibers, and lipid bilayers (e.g., cellular
membranes) are needed. Fundamental studies will allow a systematic
mapping of adsorption properties of chemical threat agents and their
analogues. Little is known about surface chemistry of G-agents, and even
less is known about the complex reactivity of VX,[^7] and their
analogues or simulants. Current detoxification, decontamination,
neutralization, and destruction schemes do not involve catalysis, and
fundamental investigations of homogeneous and heterogeneous catalysis
are warranted. Surface science studies of model compounds related to
chemical threat agents would lead to an improved understanding of the
fundamental principles of bond activation on surfaces of oxide, metals,
and supported metal catalysts. Fundamental studies are required to
develop model catalytic systems that operate at ambient temperatures and
are resistant to poisoning. The ultimate product from these studies
would be the knowledge required to design better, more efficient,
stable, and selective catalysts for chemical threat destruction with no
toxic byproducts.

Solvated electron technology (SET) is one of several alternatives tested
for chemical threat agent destruction. Little is known about details of
this reaction on molecular scale. The reactivity of solvated electrons
and reactions of materials called electrides with chemical threat agents
or suitable analogues is an area that needs further investigation.[^8]
In addition, sodium vapor reduction of CFC may have potential for
chemical threat agent destruction.

Protective clothing to guard against the effects of chemical agents will
be made of lighter weight materials than current protective suits.
Permeability of materials to chemical threats is directly related to the
underlying chemical structure of the material. Fundamental research at
the forefront of materials chemistry will lead the way to lighter weight
materials. Both military and civilian personnel need clothing that is
lightweight, inexpensive, and comfortable to wear, while providing
protection against chemical agents. Block copolymers are one obvious
candidate for such applications because of their low cost and ease of
processing.

In preliminary experiments, it has been demonstrated that linear
triblock copolymers based on a continuous phase of butyl rubber with
dispersed nanodomains of partially sulfonated polystyrene fulfill many
of these characteristics. They allow water vapor to transport through
the material while preventing the passage of common toxic chemical
agents. However, both the mechanical properties and permselectivity of
these materials require further improvement. Simultaneously, work has
been conducted that demonstrates the strong impact of changing polymer
architecture (linear diblock triblock versus branched graft copolymer
architectures) on permeability characteristics and mechanical
properties. Introduction of controlled branching into block copolymers
is thus a tool that can be used to enhance both mechanical properties
and permselectivity. Both these areas are only beginning to be explored
systematically, and much fundamental research needs to be conducted in
these areas. Small angle neutron scattering (SANS) and neutron
reflectivity are powerful tools for studying the structures of such
materials. DOE facilities for neutron studies of soft materials will be
highly utilized in these studies.

  ----------------------------------- -----------------------------------
  **Technology Need**                 **Present Problem**

  Volatile and semi-volatile chemical Fundamental studies are needed to
  agents in a confined area will      further determine the lifetime of
  adhere to surfaces and diffuse into chemical agents and TIMs in porous
  pores and open spaces.              building materials, soils, and
                                      natural environments.

  Self-cleaning and                   Fundamental research is required to
  self-decontaminating titanium       increase the photoefficiency of
  dioxide surfaces technology may not TiO~2~-containing barriers and
  be adequate for the rigors of       improve their function.
  counter-terrorism response and      
  recovery applications.              
  ----------------------------------- -----------------------------------

Volatile and semi-volatile chemical agents will dissipate in an open
environment, but in a confined area, they will adhere to surfaces and
diffuse into pores and open spaces. Decontaminating exterior surfaces
can be achieved in a number of ways; however, the pores may be
inaccessible, and the remaining material can slowly diffuse from the
pores providing long-term, low-level human exposure. Fundamental studies
are needed to further determine the lifetime of chemical agents and TIMs
in porous building materials, soils, and natural environments. Vapor
phase decontaminants are limited in number and scope, and additional
approaches to this problem are required. One approach is to apply an
overlayer of titanium dioxide (TiO~2~) material to catalytically
decompose the chemical agent or TIMs as they diffuse out of the
contaminated media. Photocatalytic materials can bring about the
oxidation of a wide range of organic and some inorganic substances.
Photocatalytic particles, coatings, and thin films have been
demonstrated to oxidize (or reduce) a very wide range of organic and
inorganic compounds at ambient temperatures, pressures, and humidities.

Self-cleaning and self-decontaminating titanium dioxide surfaces are
well demonstrated. The current technology, however, may not be adequate
for the rigors of counter-terrorism response and recovery applications.
Fundamental research is required to increase the photoefficiency of
TiO~2~-containing barriers and improve their function. The nature of
active sites involved in chemical processes at the air/solid interface
is not understood, and the mechanism of photocatalytic oxidation is
worthy of further study. The role of noble metals deposited on TiO~2~
for specific reactions is not understood, and catalyst deactivation by
inorganic reaction residues remains a problem. In addition to these
fundamental technological barriers, durable catalyst coatings for
high-wear situations and new methods to incorporate photocatalysts into
textiles and filter media are engineering challenges to be overcome in
order to apply photocatalyst to problems of response and recovery from
chemical acts of terrorism. Other technical challenges include the
development of new, light transmission materials to distribute light to
catalyst sites for uniform illumination, polymers or functional
structure coatings for photocatalytic surfaces to increase reactivity,
and formation of nano-textured surface structures to effect catalytic
activity, selective adsorption, or light adsorption.

  ----------------------------------- -----------------------------------
  **Technology Need**                 **Present Problem**

  Materials are needed that can       Current materials can't combine low
  contain or protect against the      weight, impact resistance, and low
  effects of an explosives            cost.
  detonation.                         
  ----------------------------------- -----------------------------------

In the area of explosives protection/mitigation, there is a need for the
development of materials that can be used to contain or protect against
the effects of an explosives detonation. Applications of such a material
might include containers for luggage/cargo being transported in
airplanes or other vehicles, barriers within high-security buildings,
barriers to protect VIPs at high profile events, and stronger building
materials. The desired properties of such a material would include high
blast resistance, low frangibility (i.e., if the material is breached by
a blast, it should not shatter into many airborne pieces, but should
allow pressure to escape through cracks or holes), light weight, and
low-to-moderate cost. The Federal Aviation Administration has funded
some work in this area, but fundamental materials synthesis and
processing research is needed with a focus on engineering the desired
properties into the materials.

  ----------------------------------- -----------------------------------
  **Technology Need**                 **Present Problem**

  Presymptomatic diagnosis of         Medical diagnostic tools to detect
  exposure to chemical threat agents  early signs of exposure to a
  at sub-lethal levels is needed.     chemical threat agent require
                                      development.
  ----------------------------------- -----------------------------------

An additional important aspect of response and recovery is the
presymptomatic diagnosis of exposure to chemical threat agents at
sub-lethal levels. This is particularly important in addressing social
issues associated with a terrorist chemical attack by providing a means
of gauging exposure and preventing public hysteria. Medical diagnostic
tools capable of detecting early signs of exposure to a chemical threat
agent would also reduce stress levels in the medical community under
pressure to manage a crisis situation. Biological markers of exposure to
a chemical agent will be formed, as the result of cellular processes,
long before the clinical presentation of symptoms of exposure.
Identifying the biological markers of exposure will allow early
screening and detection of exposure to facilitate treatment of only
those individuals exposed to a chemical agent. Once these marker
compounds are identified, new analytical techniques for the rapid and
confident detection of these compounds in physiological media (blood,
saliva, sputum, etc.) will be required. As in the case of detection of
chemical agents themselves, research in separations and analysis, and
materials chemistry could provide detection systems that could be used
by medical personnel to assess public exposure to chemical threats.

### Preparedness 

  ----------------------------------- -----------------------------------
  **Technology Need**                 **Present Problem**

  Needs include the development       Fundamental research is needed to
  materials and deposition processes  identify mechanisms, flaws, or film
  to fabricate bipolar thin-film      properties that limit the
  battery stacks and development of   fabrication yield for thin-film
  alternative battery chemistries for batteries.
  low-voltage batteries               

  Fieldable detection and mitigation  Fuel cell research is required.
  devices are needed.                 
  ----------------------------------- -----------------------------------

Basic research needs for improved batteries and miniaturized fuel cells
will contribute to future developments in the homeland defense area of
preparedness. Fundamental research is needed to identify mechanisms,
flaws, or film properties that limit the fabrication yield for thin-film
batteries. Mechanisms leading to degraded performance after storage or
use of batteries at elevated temperatures (60--100 °C) need to be
identified. In addition, synthetic methods need to be adapted to allow
fabrication at low temperatures, very thin, and inexpensive substrates
(e.g., plastics) and to facilitate direct integration of the battery
with integrated circuits. Development of improved packaging for the
thin-film batteries is also needed. Long-term research needs include the
development materials and deposition processes to fabricate bipolar
thin-film battery stacks and development of alternative battery
chemistries for low-voltage batteries.

Miniaturized fuel cells offer alternatives to batteries for powering
more demanding fieldable detection and mitigation devices. Fundamental
research is needed in the area of membrane technology for ion and small
molecule transport and separation. Chemical reactions and stability at
electrode-electrolyte interfaces is a topic for future research from
both experimental and computational approaches. Mechanisms of corrosion
also remain a topic of importance for the future of fuel-cell research.

## Research Needs

To seize the research opportunities discussed above and address the
scientific issues associated with countering chemical terrorism, several
research needs must be met.

### Scientific Issues

#### Miniaturized Integrated Systems {#miniaturized-integrated-systems .unnumbered}

Miniaturization and integration research themes underlie future ability
to develop inexpensive and reliable devices for first responders.
Critical research issues include microfluid and nanofluid transport,
surface treatment and functionalization, combination of top-down and
bottom-up fabrication techniques, and coupling of nanoscale and
continuum models for mass transport.

#### Chemical Recognition {#chemical-recognition .unnumbered}

Research is required to enable highly selective sensors capable of
identifying target chemicals in complex backgrounds. Critical research
topics include the use of biological or biomimetic receptor elements,
imprinted polymers, nanophase grafted polymers, and miniaturized mass
spectroscopy.

#### Interfacial Chemistry {#interfacial-chemistry .unnumbered}

Fundamental theoretical and experimental tools and models to probe
molecular interactions with solid and liquid surfaces will be critical
to development of new, selective chemical sensors, transport and fate
models for toxic chemicals that are released into a wide range of
environmental conditions, development of improved separations chemistry,
and the development of new protective barrier and catalytic materials
for protective clothing and toxin neutralization.

#### Novel Materials {#novel-materials-1 .unnumbered}

A wide range of novel and nanophase materials will be critical for the
development of new catalysts to break down chemical toxins, strong and
lightweight materials to contain explosive blasts, as well as nanoporous
and membrane materials for advanced battery and fuel cell miniaturized
power supplies.

#### Computing, Modeling, and Theory {#computing-modeling-and-theory .unnumbered}

It will be critical to fully understand and predict the equilibrium and
kinetic chemical interactions in flow fields and at solid interfaces.
Models will be important for predicting the fate of chemical toxins in a
wide range of environmental conditions and for predicting the
performance characteristics of sensors and chemical preconcentration and
sampling approaches. Modeling will also contribute to a broad range
materials development and optimization tasks associated with detection,
protection, and response to chemical threats.

#### Nanoscale Science {#nanoscale-science .unnumbered}

Many critical scientific issues and challenges associated with chemical
threats are rooted at the nanoscale behavior of materials and
interfaces. New tools for fabricating nanoscale structures, probing
structure and chemistry at the nanoscale, and modeling properties and
behavior will be needed. The Nanoscale Science Research Centers
currently being developed by BES can play a critical role in providing
the tools and research environment needed to address these critical
problems.

### Research Environment and Infrastructure

Existing BES scientific user facilities at DOE laboratories and
universities, coupled with those currently under construction, such as
the Nanoscale Science Research Centers, will provide many important
capabilities needed to address critical scientific issues associated
with chemical-based threats of terrorism. However, it is important to
recognize that because no single institution possesses all the required
assets, it is vitally important that future research programs be
multi-institutional to ensure that all research needs are met. It will
be essential to initiate collaborative projects that promote the
formation of cross-disciplinary and cross-institutional teams to address
these complex and critical challenges. For example, although surrogate
chemical threats may work fine for much of the fundamental research
discussed above, at some point it becomes important to test fundamental
principles using real chemical threats. The necessary facilities for
handling these materials safely, especially chemical warfare agents, are
not and should not be available at all DOE sites and universities. Many
tools for characterization and analysis of both hard and soft materials
will be available in the nanoscience research centers being developed at
several sites throughout the DOE laboratory system and at other existing
and developing BES resources.

The Office of Basic Energy Sciences possesses many unique resources, in
the form of scientific user facilities that can contribute to developing
the fundamental knowledge base required to counter future acts of
terrorism involving chemical threats. The four BES synchrotron radiation
light sources provide access to radiation ranging from x-rays through
the infrared region for spectroscopic and structural studies. Four
high-flux neutron sources will provide the neutron scattering and
materials irradiation resources to meet the fundamental research needs.
Four BES electron beam and micro-characterization centers are among the
world's best high-resolution electron-optical microcharacterization and
analytical facilities. These facilities will be crucial for
characterizing fundamental advances in materials research. BES-funded
specialized single-purpose centers including the Materials Preparation
Center at Ames, the Surface Modification and Characterization Research
Center at Oak Ridge, the James R. Macdonald Laboratory at Kansas State
University, and the Pulse Radiolysis Facility at Notre Dame provide
additional resources.

### Relationships with Other Programs

### Dual-Use Opportunities

The very fundamental nature of the advances required for countering
future chemical threats by terrorist organizations opens the door to
many dual-use opportunities. The more applied programs within DOE that
look to BES for fundamental scientific advances will directly benefit
from basic research applied to counter terrorism. For example,
miniaturization and integration of separations and analyses systems will
find use in field analysis for environmental monitoring in support of
remediation efforts. Small, inexpensive sensors with high chemical
selectivity will play a significant role in environmental monitoring.
Selective sensors deployed in a monitoring network can potentially save
millions of dollars each year in manual sample collection and fixed
laboratory analysis costs. New fundamental knowledge in the areas of
materials and interfacial chemistry will provide breakthrough advances
in many areas, including increased energy efficiency in lighter weight
vehicles and stronger composites for industrial applications. The
knowledge base for improved adsorption and catalytic decomposition of
chemical agents and TIMs will certainly lead to better catalytic
materials and processes for environmental restoration and environmental
protection through reduced emissions. Advances in nanotechnology are
going to influence developments in virtually every area of science and
technology, making the dual-use opportunities endless.

# Biological Threats

## Terrorism Threats and Technology Needs

The challenges we face from biological threat agents are increasing.
While microbes continue to evolve and biotechnology becomes more
powerful, the inherent hazards to humans, plants, and animals from
infectious microorganisms are greatly increased by their intentional use
by terrorists. The recent mailing of anthrax-laced letters to our
political leaders and members of the press demonstrated how simply a
pathogen can be used to kill, instill fear, and radically disrupt normal
societal activities. The need for faster and better capabilities for
warning, response, and cleanup was painfully evident as we responded to
this one case of a small-scale deployment of a noncontagious, naturally
occurring pathogen. The specter of terrorist use of other biological
agents that could result in far greater loss of life has risen in our
consciousness---agents that might be contagious or perhaps engineered
for increased virulence and resistance to our medical treatments such as
antibiotics and vaccines. In this context, we must recognize that as
microbes evolve and compete for survival, we also face naturally
emerging threats that we must be able to quickly identify and
distinguish from a suspected terrorist act.

While today's focus on bioterrorism is being driven primarily by
concerns about attacks on humans, attacks on livestock and/or crops can
be just as devastating. The recent outbreak of foot and mouth disease in
Great Britain demonstrates the devastating impact microbes can have on
livestock, and the consequent impact on food supply and economies. We
know, for example from the work of the United Nations inspectors in
Iraq, that rogue nation's have actively explored both animal and plant
pathogens as weapons. This report was written with strong reference to
attacks directly on humans, however, the science and technology base
needed to protect crops and livestock is highly related.

The biological threat is real, and we must tap into new science and
technologies in order to reduce that threat. Advances in material and
chemical sciences not traditionally applied to biothreat reduction
technology requirements hold great promise for rapid improvements in the
U.S. counter-bioterrorism posture. Fundamental advances are needed to
fill gaps in our needs and to develop the next-generation technologies
for

-   Detection and identification

-   Medical diagnostics

-   Protection

-   Decontamination and remediation

The Department of Energy (DOE) materials and chemical sciences research
and development (R&D) programs in Basic Energy Science (BES) are poised
to make significant contributions to reducing the biothreat through
scientific advances that have great potential for transition to other
developmental efforts that focus on shorter term deployment of
technology to address the biological threat, including the DOE National
Nuclear Security Administration (NNSA) Chemical and Biological National
Security Program (CBNP). A multidisciplinary approach that leverages
advances in the chemical and physical sciences holds great potential for
decreasing our vulnerabilities. The advances envisioned in this report
would provide quantum leaps in technology that will alter existing
approaches to prevention, response, and mitigation of the biological
threat. In addition, the technology will enjoy wide application in
resolving related public health challenges from infectious diseases.

The Department of Defense has addressed the biological threat in the
context of the battlefield. However, biothreat reduction in the context
of the civilian population is very different. For example, the average
civilian is not trained or equipped for response, the public health
system is not supported with the kind of central command and control
systems associated with the military, different requirements exist on
sensitivity and different levels of tolerance for false positives and
false negatives, and there is a need for dealing with a broader set of
potential agents. Also, much higher sensitivity is required for Counter
Terrorism (CT) detection, raising substantial technology challenges and
the need to assess background interferences that will be much more
significant for low-level detection/monitoring issues.

Scientific research and technology development to reduce the threat from
bioterrorism must be conducted in an environment that has strong
multidisciplinary capabilities, that includes biology along with
materials and chemical sciences, that has the infrastructure to support
large teams and projects, and that has the ability to separate and
compartmentalize work that must be classified or protected while still
being able to attract the best scientists and technologists.

The technological challenges that need to be addressed are significant
and diverse. Some examples that will be specifically addressed in this
report are the following:

> *Environmental backgrounds.* In general, backgrounds are complex with
> an imponderable diversity of biology. They are not well characterized,
> are highly variable (in time and space), and can contain measurable
> levels of the \"smoking gun\" chemicals from normal industrial
> activities. False positive and false negative detections of biological
> agents will be extremely unpredictable without a more thorough
> understanding of the chemical and biological environments being
> sampled.
>
> *Transport and transformation in the environment.* Understanding the
> fate of signature species in the environment is required to minimize
> large uncertainties. Few studies have examined the natural
> distribution and survival capabilities of pathogens like *Bacillus
> anthracis* in even the most common environments.
>
> *Sample collection.* Means for collection, concentration, and
> separation of low-level agents in highly variable, complex
> environments are required for reliable detection of many agents. The
> development of materials and systems that achieve this task with high
> efficiency is a significant challenge.
>
> *Development and characterization of new materials.* New materials for
> many applications are needed (e.g., remediation and decontamination
> materials that can be rapidly deployed to mitigate initial impacts and
> that are environmentally friendly, coatings and materials to protect
> against hazardous substances, and materials for new sensors and
> diagnostics).
>
> *Coupling sensitivity, selectivity, and reliability**.*** Many systems
> with the required sensitivities are prone to false alarms.
>
> *Developing durable and reliable unattended systems**.*** To achieve
> broad area surveillance, some detection systems may need to be left in
> place with little oversight for years of time and need to be stable,
> subject to reliability checks, etc.
>
> *Speed**.*** High-speed, secure, reliable information flow can be
> critical to screening of high volumes of materials (e.g., travel bags,
> shipping containers) or providing adequate time for a response (e.g.,
> shutting down an air handling system or taking some neutralizing
> counter-measure).
>
> *Complexity.* The ability of biological agents to mutate or to be
> manipulated and the inherent diversity of the biosphere are challenges
> in this regard. Also, large volumes of complex data need to be
> processed and analyzed rapidly in order to make sound decisions (e.g.,
> through artificial intelligence).
>
> *Development of new trigger systems.* Rapid response to bioterrorist
> threats has been hampered by the focus on initial detection that
> relies upon highly specific and expensive detection systems.
> Techniques that detect simple environmental changes that are easily
> measured (e.g., rapid increases in total bacteria numbers or highly
> conserved biosignatures unrelated to any other changes in the
> environment) could provide much better and cheaper initial warning
> systems for first responders.

## BES Research Accomplishments and Implications

DOE's Basic Energy Sciences program has supported research and
development in many areas that are critical to advancing our
capabilities for addressing the emerging biological threat, including
the threat posed by potential terrorism. These areas include basic
research and technology development relating to molecular recognition,
integrated molecular systems, interfacial science, novel materials
development, nanoscience and technology, spectroscopy, computing,
modeling and simulation, and integrated devices, as well as advanced
instrumentation and the development of large-scale facilities for
materials and molecular characterization. A few examples are given here
of BES research accomplishments that highlight fundamental advances in
these areas.

### Nanophase Materials

BES is one of the larger sponsors of research that addresses fundamental
issues controlling the synthesis, characterization, and properties of
nanophase materials. Materials that are structured on the same scale as
the molecular machinery of life offer extraordinary approaches to
address complex biological problems. Current research is being pursued
in areas including the development of new semiconductors for
spectroscopic analysis of bio-agents, membranes and nanoporous materials
for detection and protective applications, and nanocrystals that can be
used to provide new approaches for molecular recognition for detection,
medical diagnostics, and response and recovery.

Nanoparticles for Novel DNA and Protein Sensing Technology

BES-sponsored research has led to the development of new methods for
chemically coupling biomolecules to metal oxide nanoparticles, opening
up opportunities for development of new families of electronic sensors
of DNA hybridization (bio-chips), protein binding, and in situ DNA
imaging. Single-strand DNA-linked nanoparticles retain the ability to
hybridize to complementary DNA and to carry out sequence-specific,
light-triggered DNA recognition. Light-generated silver deposition on
metal oxide nanoparticles is observed only when attached DNA sequences
are in a double helix form. This allows the electronic sensing of the
DNA double helix, as well as the development of new electrochemical
probes for DNA-binding. This system also extends to detection of DNA
binding polymers because of a change in redox properties of DNA after
binding to proteins as well as detection of protein-protein
interactions.

> *\[Argonne National Laboratory\]*

+-----------------------------------------------------------------------+
| > ![](media/image5.wmf){width="3.6013888888888888in"                  |
| > height="2.0381944444444446in"}                                      |
| >                                                                     |
| > **SQUID-Based Pathogen Detection**                                  |
| >                                                                     |
| > BES sponsored researchers are developing a sensitive, fast, and     |
| > versatile new technique for detecting pathogenic organisms or       |
| > molecules using a "microscope" based on a Superconducting Quantum   |
| > Interference Device (SQUID).                                        |
| >                                                                     |
| > \[Lawrence Berkeley National Laboratory\]                           |
+-----------------------------------------------------------------------+

Host-Pathogen Interactions Probed Using Neutron and X-Ray Scattering

Neutron and x-ray diffraction and reflectometry experiments being
performed at the BES-supported Los Alamos Neutron Science Center have
been used to probe the molecular recognition interaction of cholera
toxin with its natural receptor, GM1, on a cell membrane surface.
Binding of the cholera B5 subunit to a phospholipid monolayer containing
GM1 in a Langmuir Blodgett trough results in an ordered array of cholera
with electron density distribution shown in the Figure. Binding of the
full cholera protein, AB5, results in disruption of the order in the
aliphatic portion of the phospholipid monolayer, possibly indicating
incorporation of the A subunit into the membrane. Improved models for
toxin molecular recognition can contribute to the development of new
biomimetic sensor technology as well as the development of improved
human vaccines.![](media/image6.wmf){width="2.4930555555555554in"
height="2.2069444444444444in"}

*\[Los Alamos National Laboratory\]*

+-----------------------------------------------------------------------+
| > ![](media/image7.wmf){width="1.9229166666666666in"                  |
| > height="2.625in"}                                                   |
|                                                                       |
| Nanostructured, Interfacial Materials for Biosensors                  |
|                                                                       |
| BES-supported research is exploring the use of templated              |
| self-assembly approaches to create nanoporous inorganic materials and |
| hybrid organic/inorganic materials that could serve as novel          |
| platforms for bio- or chem-sensors and as separation elements in      |
| purification and filtration devices. While molecular self-assembly is |
| routinely used to precisely control nano-scale porous materials, new  |
| research focuses on the co-assembly of soft organic structures within |
| more robust inorganic scaffolds. Specific examples include the        |
| co-assembly of lipid bilayers within sol-gel silica meso-porous       |
| materials. Results show that the co-assembled lipid membranes retain  |
| their biomimetic sensing capabilities while the hybrid composite      |
| material provides greater stability and ease of processing. The       |
| emphasis of this research is on the                                   |
|                                                                       |
| development of material preparation strategies, on characterization   |
| of the resulting materials, and on understanding the interaction of   |
| these materials with other nanostructured components such as          |
| biological membranes or electronically active macromolecular systems. |
|                                                                       |
| *\[Los Alamos and Sandia National Laboratories\]*                     |
+-----------------------------------------------------------------------+

### Interfaces

The structure and properties of interfaces between living systems and
man-made materials play an extremely important role in technologies
related to the detection, medical diagnostics, protection, and response
to biological threats. BES research has led to the development and
application of experimental and theoretical tools that are providing new
insights into the structure and dynamics of these interfaces.
Developments include local and scanning probe techniques for measuring
structure and molecular interactions, time resolved spectroscopic tools
to examine interfacial energy transfer, X-ray and neutron tools to
determine detailed molecular structure, and a wide range of
computational tools.

###  Integrated Systems

Integrated systems for chip-based detection and diagnostics are already
being developed to counter biological terrorism threats. BES research
has played a pioneering role in the development of these technologies by
providing underpinning science addressing microfabrication, integration
of new materials and synthesis approaches, fluid and energy transport at
small dimensions, and the control of interfacial properties and
interactions.

### Atomic and Molecular Spectroscopy

Advanced spectroscopic tools being developed in BES research programs
have significant impact on technologies for detection and source
attribution of biological agents. Developments included high-resolution
mass spectroscopy for identifying bacteria or other biological agents,
laser-based spectroscopy for both microanalysis and stand-off detection
and identification of bioagents, and nuclear isotope detection that can
help in identifying the source of specific bioagents.

In addition to the individual research projects highlighted above, BES
is developing a major new initiative to establish a number of Nanoscale
Science Research Centers: Molecular Foundry (LBNL), Center for Nanoscale
Materials Sciences Science (ORNL), and Center for Integrated
Nanotechnology (Sandia/LANL). The research centers will provide
facilities and support collaborative research that will bring together
the best researchers in the national laboratories, academia, and
industry with the latest technologies to carry out breakthrough research
and development in nanoscience and technology. These intellectual and
resource centers will be major assets in advancing the research and
development needed for biothreat reduction applications described in
this report.

Finally, BES is steward of a number of the nation's major facilities for
materials and molecular characterization; specifically synchrotron
(Advanced Photon Source, National Synchrotron Light Source, Stanford
Synchrotron Radiation Laboratory, Advanced Light Source) and neutron
scattering (Spallation Neutron Source, High Flux Reactor \[HIFR\],
Intense Pulsed Neutron Source, and Los Alamos Neutron Science Center)
facilities that each year serve hundreds of users. These facilities will
play a key role in advancing the materials and chemical sciences
underpinning advances in biothreat technologies.

Biocavity Laser for Real-Time Detection of Pathogens

BES-funded research on nanostructured compound semiconductor light
emitters has supported the development of a highly sensitive micro laser
device, the Biocavity Laser. Consisting of a microfluid channel
introduced into the optical cavity of a quantum-well semiconductor
laser, the Biocavity Laser has been successfully demonstrated for
rapidly screening human cells for abnormalities (e.g., brain tumors and
sickle cell anemia). The power of this approach relies on the intimate
coupling of solid-state nanostructured materials with living biological
systems. Operationally, the bio agent, suspended in a fluid, enters the
optical cavity of the laser via the microfluid channel and becomes a
part of the cavity, impressing bio agent information on the spectral
output of the laser. Spectral analysis using a laptop computer leads to
the identification of the agent. While this work has focused on human
disease detection, it is directly applicable to the rapid identification
of potential biowarfare agents in the form of tiny pathogens like
bacteria, spores, or viral particles.

*\[Sandia National Laboratories\]*

^1^ P. L. Gourley and D. Y. Sasaki, "Biocavity lasers*," American
Scientist*, v. 89(#2) pp. 152-159 Mar-Apr 2001.

> ![](media/image8.jpeg){width="4.9875in" height="3.6305555555555555in"}

Mass Spectrometry Based Bio-Agent Detection

Fourier Transform Ion Trap (FTICR) mass spectrometry has already
demonstrated. Preliminary work has already demonstrated the usefulness
of this approach, providing advanced designs that have many of the
features needed for reliable field instrumentation with the required
performance. It has the required mass range, sensitivity and resolution.
However, significant advances are needed to turn this instrument into a
sufficiently small, rugged, reliable, and easily used instrument for
routine work outside a research laboratory. To this end, numerous issues
associated with the fundamental physics of these instruments are being
investigated in BES research projects. Perhaps the most important
problems are those associated with electric and magnetic field
quality.![](media/image9.wmf){width="1.9111111111111112in"
height="1.9347222222222222in"}

*\[Pacific Northwest National Laboratory\]*

## Scientific Issues and Opportunities

To keep the focus clearly on the goals of biothreat reduction, this part
of the report is organized around the four critical application areas
broadly recognized as key to our ultimate defense against biological
threats: (1) Detection and Identification, (2) Medical Diagnostics, (3)
Protection, and (4) Decontamination and Remediation. Each of these areas
will be discussed in terms of the specific scientific issues and
opportunities. The common themes emerging from these discussions are
summarized at the end under Research Needs, which will also consider
infrastructure, research environment, and relationship to other
programs.

### Detection and Identification

  ----------------------------------- -----------------------------------
  **Technology Need**                 **Present Problem**

  Identify biohazards in wide variety Need improved techniques to rapidly
  of ambient settings.                and selectively sample biohazards
                                      from complex biomaterial
                                      backgrounds.
  ----------------------------------- -----------------------------------

Here we consider detection and identification technologies needed across
the full spectrum of intervention scenarios: indications and warning,
environmental surveillance, diagnostics, residual hazard surveys, and
attribution and forensics*.* The key attributes required for effective
detection and identification technologies across this entire spectrum
include high sensitivity, specificity, speed, no false positives or
false negatives, reliable discernment of targets against complex
backgrounds, simple operation, inexpensive to deploy for broad coverage
devices, systems integration, and size (potential for miniaturization,
microfluidics, portability). We will consider these attributes as we
address the issues and needs for different phases of detection: sampling
and collection, triggers, early warning and point sensors, and
characterization and forensics.

#### Sampling and Collection {#sampling-and-collection .unnumbered}

Biohazards will be presented in the context of an already complex
environment that is rich with materials that both dilute and interfere
with the intended detection signal. Sampling technologies are required
to improve the sensitivity and specificity of detection and analysis
methods for assessment of contamination of the environment as well as
the related personnel and surfaces. Of particular importance is the
characterization of aerosol hazards using systems that can be automated
and allow operational simplicity. System attributes should include means
for selective concentration of the species of concern to avoid
complications from the widely varying and complex background.

***Extraction, Purification, and Concentrating Technologies.*** There is
a clear need for novel technologies for the extraction, purification,
and concentration of bio-agents. Key to this technology will be
molecules that exhibit very high affinity and specificity for the agent
of interest. These molecules may be synthetic, such as abiotic
receptors, polymers imprinted to achieve high specificity, or biological
molecules selected from large, diverse libraries for their high affinity
and specificity to the agent of interest, such as single-chain antibody
variable domains. Methods to engineer high stability into these specific
ligands represent an important challenge for this problem, as well as
the development of detectors and point sensors discussed below.

Affinity purification will require molecules designed for specific
recognition and binding followed by reversible release of the targets so
that they can be recovered. Scaling down to the use of microfluidic
devices, including flow cytometry to select specifically labeled cells
or size selected cells and the ability to lyse cells for further
analysis, are all capabilities that need to be developed significantly
to make possible extraction of agents from small, dirty samples in the
field. New materials for separations, such as novel polymer resins for
column chromatography will need to be developed that are robust,
reusable, and inert to environmental contaminants.

***Sampling and Collection Materials.*** Selective adsorbents for
pathogens that are compatible with biomaterials are needed to collect
environmental samples from both the aqueous and gas phase. These
materials must be designed both to specifically entrap the pathogens,
via molecular or shape recognition, and to maintain the biomaterial's
structure and function. Molecular or shape recognition can be pursued
using biologically or synthetically derived receptors that can be
engineered onto various surfaces/materials. The supporting surface or
material must not only support functionalization for specific binding of
the biomaterial, but must also be engineered to resist nonspecific
adhesion of the biomaterial. Besides the main issue of nonselective
capture of the biomaterials from the environment, nonspecific adsorption
of biomaterials can lead to numerous additional problems. For proteins,
nonspecific adsorption often will lead to denaturation, thereby changing
the function of the protein as well as its affinity characteristics to
sensor systems downstream. Denaturation also can mean tenacious binding
of the protein to the surface and thus ineffective desorption of the
protein for subsequent identification. Cellular adhesion to surfaces can
also run into similar problems and even lead to cell lysis, again
rendering downstream detection schemes useless. Surfaces coated with
polymers (e.g., surface grafted polymers, block copolymers, or
dendrimers) or self-assembled materials (e.g., SAMs, lipid bilayers, or
liquid crystals) with unique functionality (e.g., PEG, PNIPAM, or
polysaccharides) have proven effective as biomaterial-passive coatings,
but further advances in the materials with regard to molecular-level
structure, nano- and micro-scale patterning, functional group
orientation and placement, and post-functionalization capability would
greatly improve upon existing systems.

The sampling and collection materials must not only possess the ability
to capture the bioagent but must also reversibly desorb the captured
agent. In that sense, the receptor sites, and the material, must have
either reasonably low on/off rates, such that relatively small changes
in temperature can effect biomaterial desorption, or the ability to
reversibly alter its structure to reduce ligand affinity on command.
Reversible structure schemes could be triggered by temperature, light,
or chemical treatment. For any scheme to succeed, the material must be
robust to the physical or chemically changes used to impose desorption.

#### Triggers  {#triggers .unnumbered}

  ----------------------------------- -----------------------------------
  **Technology Need**                 **Present Problem**

  Simple, inexpensive triggers that   Current biomolecular analysis
  alert the need for detailed         approaches not suited to widespread
  biohazard analysis.                 and continuous applications.

  Stand-off detection of biohazards.  Laser-based techniques must become
                                      more portable with greater range
                                      and sensitivity.
  ----------------------------------- -----------------------------------

It can be very expensive and challenging to deploy sensing systems that
detect biological agents with reliability adequate for taking actions
that may have major economic impact or cause significant societal
disruption. An alternative is to deploy less definitive and less
expensive devices for providing information that would "trigger" further
analysis and sample collection for definitive decision making. Trigger
sensors fall into two general types, point sensors and stand-off
sensors. Point sensors are described in their own section as they can
play roles as either trigger of definitive sensors depending on their
characteristics. We consider here the needs for development of improved
stand-off sensors.

***Laser-Based Remote Detection Methods.*** Laser based detection
systems are inherently capable of remote real-time characterization.
Their value as triggers for biothreat agents will be determined only by
research leading to the development of advanced tools to enable
exhaustive characterization of ambient microflora versus biothreat
clouds, demonstration of detection above background, and identification
of organisms in different states. Next generation instruments will be
more portable, more sensitive, lower in cost, and more reliable. X-ray
fluorescence and synchrotron FTIR may prove to be valuable tools for
obtaining materials properties leading to remote trigger detection
methods. Creation of mathematical tools (e.g., artificial intelligence)
for the extraction of reliable information from large volumes of complex
data will be a valuable adjunct to any trigger system.

Fundamental issues that must be addressed include a lack of basic
spectroscopic data for bio-particles such as bacteria, improvement in
overall sensitivity for all of these methods, sampling statistics, and
the ever-present issue of eye safety that must be adequately addressed
if such instruments are ever to find widespread use in commercial and
industrial environments. High-throughput applications may require new
imaging detection systems with improved sensitivity. Examples of three
applications of lasers to remote sensing are given below.

> *Laser Induced Breakdown Spectroscopy (LIBS).* Characterization of
> many solid materials, including single particles, can be accomplished
> using LIBS, an atomic emission spectroscopy technique that uses a
> laser-induced microplasma for the highly efficient dissociation of the
> components of fine particulates (\~10 microns diameter) producing
> light emission characteristic of the atomic constituents. Detection of
> the emission can be used for chemical analysis at a distance of up to
> 24 m and for about 75% of the known elements. Research is needed to
> evaluate and extend the sensitivity (current detection limits are of
> the order of tens of ppm for most elements) and selectivity of this
> technique for characterization of aerosol dispersed biological agents,
> as well as chemical agents and explosives.
>
> *Laser Induced Fluorescence (LIF).* For substances that luminesce,
> which include most bioaerosols and many organic aerosols, LIF is a
> sensitive remote characterization method.^1,2^ Detection of small
> molecules can be highly sensitive with limits of detection in the tens
> of parts per trillion levels.^3,4^ The simple presence of particle
> luminescence can be used to distinguish between biological and
> nonbiological particles, and the spectra of individual particles can
> often be used for more detailed identification. Successful
> applications have included detecting allergens and spores. However,
> spectral similarities have made it difficult to identify specific
> bacteria. Research is needed to better understand the photophysical
> processes leading to fluorescence from dispersed biological agents to
> extend the diagnostic potential of LIF for stand-off detection in
> complex atmospheric environments. A modification to the LIF method as
> applied to volatile explosives at the ppb levels is to perform
> laser-induced photodissociation on the species of interest and then
> measure LIF of a fluorescent fragment molecule.
>
> *Laser Raman Spectroscopy (LRS).* An inherently remote method, LRS can
> provide functional group specific spectral information over a distance
> of tens of meters. Recent advances in laser Raman spectroscopy are
> from the development of spectroscopic systems using UV excitation for
> resonance enhancement, near-IR excitation for freedom from
> fluorescence background, sensitive array detectors, and Fourier
> transform techniques. Research is needed to continue the recent
> advances in spectral selectivity (i.e., using acousto-optic tunable
> filters) and sensitive optical detection schemes. Raman
> characterization of individual particles currently requires that the
> particle under study be held stationary using relatively simple
> electromagnetic or electrostatic particle traps in order to have
> sufficient time to acquire adequate signal-to-noise ratios. Spectra of
> particles of less than 1 μm diameter have been obtained in this
> manner. While these techniques have so far only been used in the
> laboratory, they could be promising approaches for field detection of
> a wide variety of toxic particles in air. Researchers have found that
> bacteria can be readily distinguished by their Raman spectra, as can
> explosives. Raman spectroscopy is the least sensitive of the laser
> techniques but can be the most specific.

#### Early Warning and Point Sensors  {#early-warning-and-point-sensors .unnumbered}

  ----------------------------------- -----------------------------------
  **Technology Need**                 **Present Problem**

  Point sensors for early warning     Present sensors cannot combine
  detection.                          rapid, sensitive and specific
                                      detection.

  Real-time continuous biohazard      Sensors will have to become more
  monitoring.                         robust, reliable and able to
                                      operate at low power in air.
  ----------------------------------- -----------------------------------

Advanced point sensors for environmental detection of biological
pathogens are critical for early warning and for assessing possible
contamination. Sensor systems capable of rapid, sensitive, and specific
detection of biothreat agents are needed to deal with not only the
terrorist threat, but also naturally emerging biological threats.
Environmental point sensors could be used by first responders (firemen,
police, hazmat personnel, etc.) as portal monitors or in sensor
networks. The sensors must be simple, robust, reliable, compact, and, in
many instances, battery operated. They must also be able to
differentiate between pathogens in the context of the inherently complex
environment. These attributes are difficult to achieve for environmental
sensing. Moreover, there is a pressing need for real-time and continuous
monitoring, and for the sensor system to operate directly in air with no
prior aerosol collection. What is addressed here is the basic science
that underpins the development of advanced sensor systems and entirely
new detection methods.

***Molecular Recognition.*** Molecular recognition (the process by which
two molecules come together, recognize one another, and initiate the
process by which they finally bind in a specific, high-affinity
interaction) is one of the most important processes in any technology to
detect biological (or chemical) agents. However, the chemistry and
physics of the recognition process, which involves initially weak
interactions, are poorly understood. Questions that arise when
considering molecular recognition in the biological arena are: How does
the binding site of proteins convert from a typically disordered state
to one that achieves strong ligand recognition? How does a disordered
loop of peptide on the surface of a protein recognize a small molecule?
How can the interaction of the small molecule lead to the formation of a
stable, protein--small-molecule complex? How is the specificity and
affinity of the interaction coded into the structure of the binding
partners prior to their interaction? We need to find answers to these
fundamental questions to make progress in engineering host-guest
complexes that will be important for design of sensors, whether they use
biological or inorganic molecules as components.

> *Engineering of Robust Ligands**.*** There is a huge need for highly
> specific ligands that are robust for use in field detectors, as well
> as in collection devices. One option for these ligands is to use
> polymers treated by molecular imprinting to provide specificity.
> Another approach is to utilize carbohydrates and small peptides (7--20
> mers) that are inherently stable.^5^ Both of these approaches satisfy
> the need for stability but suffer from low affinities and relatively
> poor specificity owing to cross reactivity to multiple biomolecules. A
> third method is the engineering of proteins or DNA/RNA aptamers
> obtained from large, diverse molecular libraries.^6,7^ For instance,
> antibodies have many properties that are highly favorable for use in
> sensors (or collectors), but often lack the stability required for use
> in the field or for long-term storage. Structure-based engineering of
> antibody domains can be used to create hyper-stable, single-chain
> variable domains. Alternative approaches involve the use of other
> scaffolds that have greater intrinsic stability.
>
> *Structural Biology of Surface Epitopes and Macromolecular Complexes*.
> Protein-based detection of bioagents will depend on interaction of a
> detector molecule(s) (such as a single-chain antibody variable domain)
> and a surface epitope of the agent. Characterization of the surface
> epitopes can be carried out either through the crystallographic
> analysis of structural proteins that make up the surface of the
> agent,^8^ or through epitope analysis using libraries of antibodies
> displayed on the surface of phage particles. Screening of antibody
> libraries will lead to the identification of those with affinity for
> surface epitopes of the agent. The epitope can then be identified by
> screening peptide sequences, which may or may not be derived from the
> gene of interest, displayed on the surface of phage particles.
> Characterization of the specificity of the antibody will provide the
> identification of the epitope. Identification of these epitopes is a
> significant step towards an understanding of the parameters needed for
> vaccine design, design of drugs targeting the adhesion molecules of
> the agents, or the design of drugs involved in agent neutralization.

***Signaling and Amplification.*** Cell signaling in nature is an
exquisitely sensitive molecular cascade that converts a highly specific
molecular recognition event to a macroscopic change. Nature does this by
directly coupling a molecular recognition event to a signal, often a
structural change that is then amplified through the enzymatic
production of secondary messenger molecules that open, for example, ion
channels. There is continued need to develop new molecular transduction
approaches that mimic cell signaling in increasingly innovative ways.

Examples of recent advances in signal transduction and amplification
include the coupling of novel electronic and photonic materials to
recognition. Conducting polymers have been used to provide amplification
through the fluorescence quenching of the entire polymer by a single
molecule.^9^ Similar approaches have been taken with carbon nanotubes
and related "molecular" wires to provide exquisitely sensitive response
to a molecular-level event. Molecular recognition has also been used to
open and close ion channels to provide signal amplification that mimics
nature.^10^

In addition to new transduction approaches that build on novel new
materials, entirely new approaches are needed to provide the level of
specificity and sensitivity inherent in high-affinity recognition
ligands yet with lower affinity permitting continuous monitoring.
Current approaches based on immuno-assays are, in effect, irreversible.
Mammalian olfaction is an example of how nature utilizes low affinity
but highly specific recognition to achieve rapid reversibility of an
event and avoid saturation. The development of new sensing approaches
that build on biomimicry and biomimetic materials could well provide the
underlying scientific foundation for near real-time continuous monitors
for environmental sensing of threat agents.

***Interfacial Phenomena.*** Sensors that are based on mimicking
biological recognition and response must be able to interface the
biomimetic system with a sensor platform that can interpret the signals.
Biochemically based identification devices correspondingly require
quantification tools that approach single molecule sensitivities.
Moreover, technologies that have features with small (\< 10 µm) length
scales necessarily have high surface-to-volume ratios increasing the
importance of understanding interfacial chemistry. Understanding how
ultrasensitive spectroscopy and interfacial phenomena interrelate is
fundamental to developing more sophisticated, robust sensors.
Spectroscopic probes can be applied to condensed-phase systems and have
applications in both biological and materials sciences.^11,12^ These
ultrasensitive laser-based probes have been used to interrogate physical
and chemical interactions in micro- and nano-domains and at interfaces.
These probes can now be used to study systems where biological or
biomimetic molecules interact with hard and soft materials.

***Dry Sensors.*** Environmental sensing of biological markers generally
requires an aerosol collection followed by sample injection. It would be
highly desirable to develop sensors that could directly respond to
biological markers dissolved in aerosols without first concentrating the
aerosol. Such "dry" sensors may need a permeable barrier material that
separates the air to be monitored from the active element of the sensor
system. Mesoporous materials (sol-gel, hydrogel, aerogel,
block-copolymers, etc.) with controlled pore size and character
(hydrophilicity and functionality) could be used to separate the air to
be sampled from the active sensor elements. Ideally, these would be
hybrid materials where proteins or genes could be, for example,
electrophoretically (or physically) driven across the membrane barrier
into the active sensor region. Other transduction approaches that use
biomimetic materials that incorporate recognition and reporter molecules
in a stable fluid media (e.g., membrane mimetic architectures) also have
promise as dry sensors.

***Single Particle Methods.*** Instrumentation is becoming available for
the rapid, real-time analysis of individual aerosol particles. Such
instrumentation can be highly diagnostic, as it does not average
information about a specific agent with that from background
constituents---finding the needles in the haystack by rapidly looking at
a large number of individual "straws." Many field-portable instruments
have been developed that follow an initial sorting of the aerosols by
their aerodynamic size with a volatilization, fragmentation, and
ionization step (sometimes through the use of lasers) and mass spectral
characterization of the ionic fragments.^13,14^ Instruments using ion
traps for mass analysis are especially powerful because of their MS/MS
capability, permitting the generation of sequence tags for protein
identification, for example.^15,16,17,18^ Research into laser material
interactions is needed to improve the quantitative aspects of such
instruments, with particular attention to characterization of biological
agents and explosive materials. Aerodynamic sorting can also be followed
by deposition of the aerosols on a substrate for later laboratory
analyses. Recent advances allow elemental analyses on tens of thousands
of individual particles (as small as 0.1 μm) to be performed via
automated electron induced x-ray emission detection. Advances in
high-resolution mass spectrometry indicate the potential for direct
biological species identification through detection of highly specific
signature molecules, following laser ablation of molecules from the
surface of an individual spore, for example. These recent examples show
that there is much to be gained in the speed and certainty of detection
of biological agents through additional research into methods of single
particle analysis.

***Miniaturization**.* Among the technologies needed for addressing the
identification of biological threat agents will be microfabricated
devices. Different aspects of R&D needed to achieve miniaturization will
be described here.

> *Microfluidics.* Microfluidics enables samples and reagents to be
> easily manipulated, analyzed, and detected "on-chip." This suggests
> the eventual ability to perform virtually any type of "wet-chemical"
> bench procedure on a microfabricated device.^19,20,21^ This moving of
> the chemical or biological laboratory to a microchip includes the
> advantages of reducing reagent volumes, automating material
> manipulation without human intervention, reducing capital costs,
> parallel processing, faster analysis, and remote operation away from
> large laboratories. The volume of fluids manipulated or dispensed in
> the microfluidic structures depends on the channel dimensions but is
> typically on the order of picoliters to nanoliters. By implementing
> multiple processes in a single device (serial integration), these
> small fluid quantities can be manipulated from process to process
> efficiently and automatically under computer control. An operator
> would only have to load the sample to be analyzed. This serial
> integration of multiple analysis steps can be combined with parallel
> processing by replicating microfabricated structures on the same
> device.
>
> Although significant progress has been made, microfluidic devices need
> to reach the next level of sophistication to contribute significantly
> to deterring terrorism. Fundamental research issues include materials
> development, novel fabrication techniques, fluid transport phenomena,
> and system integration. Developments with microfabricated fluidic
> devices would need to parallel advances in biochemical assays for
> future integration.
>
> *Nanofluidics.* Understanding the chemistry and physics of molecular
> transport through fabricated channels with molecular-scale lateral
> dimension is fundamental to developing the next generation of
> biological sensors. Although such transport is fundamental to life,
> there is little molecular scale understanding of the requirements for
> such processes. Studying such phenomena using well-characterized
> nanometer scale channels fabricated in substrates such as silicon,
> quartz, or other materials is one approach.^22,23^ Fundamental
> transport issues for fluids and solutes need to be studied within
> these nanoscale conduits.^24,25^ These studies should include
> chemistry and physics issues related to hard materials (the materials
> that form the fluid enclosures), soft materials (fluids, molecular
> coatings, and biological molecules), and the interface between the two
> types of materials. Fundamental questions that need to be addressed
> include phase transitions and scaling of polymer transport through
> nanoconduits, the validity of continuum fluid mechanics at the
> nanoscale, and fundamental limits of forming nanoscale conduits.
>
> *Miniature Gas Phase Analysis; Mass Spectrometry*. The inherent
> selectivity and speed of mass spectrometry has the potential to
> provide significant capability for rapid identification of biological
> agents. The idea of advanced, selective miniature mass
> spectrometer-based sensor systems is intriguing.^26,27^ Experimental
> and computational approaches to study the fundamental chemical and
> physical processes that permit the reduction of size, cost, and
> analysis speed for mass spectrometer systems would be needed. Evidence
> suggests that the fundamental processes underpinning laboratory scale
> mass spectrometry will not scale with size when moving from the
> centimeter to the micrometer domain (and beyond). Thus, transitioning
> mass spectrometry from laboratory to small-scale (hand-held) sensor
> devices will require the study and understanding of fundamental
> phenomena in the new size regime both to determine the limits of scale
> as well as to identify and exploit new opportunities. These phenomena
> include ion transport, ion energetics, and gas phase ion and ion-ion
> chemistry at micrometer dimensions.^28,29^

#### Characterization, Attribution, and Forensics  {#characterization-attribution-and-forensics .unnumbered}

  ----------------------------------- -----------------------------------
  **Technology Need**                 **Present Problem**

  Rapidly characterize and attribute  New methods must provide rapid
  the origin of biohazard material.   species analysis and stain specific
                                      detection.
  ----------------------------------- -----------------------------------

For bioagent characterizations, a variety of technologies ranging from
compact fieldable sensors to elegant laboratory-based bioanalytical
methods are needed. The discussion above for sample collection and
environmental point sensors applies equally to forensics and
attribution. Forensics and attribution can also be achieved by isotopic
and elemental analysis of nonbiological constituents of a sample, as
well as by DNA analyses for the species and strain identification.
Analysis of DNA variations using Amplified Fragment Length Polymorphism
(AFLP), Multiple Locus Variable number tandem repeat Analysis (MLVA),
and single nucleotide polymorphism (SNPs) have proven invaluable in
characterizing agents. These DNA-based techniques will remain important,
but we also need novel methods that will provide for faster analysis for
species and, if possible, strain-specific detection and
characterization. In this section, we will concentrate on technologies
needed for attribution and forensics applications of isotopic analysis
and high-throughput bioassays.

***Isotopic Signatures for Attribution.*** Sensitive techniques for
stable isotope separation provide a means of determining the origin of
biological agents in forensic reconstructions. A specific example of
this kind of application is the potential use of Sr and Pb isotopic
compositions in tracing the source of the anthrax causing B. anthracis
recently sent through the mail system, either through the composition of
the spores themselves or of their carrier medium. In the natural
environment, different sources of Sr and Pb can have different isotopic
compositions because of decay of ^87^Rb to ^87^Sr, ^235^U, ^238^U, and
^232^Th to isotopes of Pb, coupled with variable time integrated Rb/Sr,
U/Pb, and Th/Pb ratios in different natural materials. This variation,
related to underlying regional geology, imparts to different fresh-water
sources contrasting Sr and Pb isotopic composition that can be used to
constrain geographically the source of fresh water. For example, water
from the Connecticut River has a distinct range in Sr and Pb isotopic
composition from water from the Sacramento River (in contrast, while the
Pb isotopic composition of seawater is variable, the world's oceans are
essentially homogeneous in Sr isotopic composition). Likewise, the trace
amounts of Sr and Pb in chemical reagents are likely to have distinct
isotopic compositions. When Bacillus anthracis sporulates, it
incorporates small amounts of Sr and Pb, faithfully recording the Sr and
Pb isotopic composition of the growth medium. This provides then an
isotopic fingerprint of the source of the spores. This can be used to
not only compare different aliquots of the spores, but could also
potentially provide clues to the geographic origin of spore production
or to sources of utilized reagents.

***High-Throughput Assays for Agent Characterization.*** There are many
instances (e.g., distinguishing a pathogenic agent from a vaccine
strain) where it is critical to be able to rapidly characterize
biothreat agents in the field.

> *Gene Probe and Protein Chip-Based Assays.* Immunological (protein
> based) and DNA or RNA (gene based) detection currently provides
> sufficient accuracy for identification and characterization.
> Microarrays provide an efficient way of performing large numbers of
> nucleic acid hybridizations or protein-protein interactions
> simultaneously, but there are challenges concerning costs and quality
> control. They rely at the moment on the arraying of nucleic acids or
> proteins on glass slides or membranes. Protein arrays still rely on
> sandwich assay formats that require both capture and reporter
> antibodies. For this reason, protein arrays suffer from problems of
> relatively low affinities (the weaker of the antigen\'s affinities to
> the capture or reporter antibodies) and higher levels of cross
> reactivity relative to gene arrays.^30^ New reagent-free assay formats
> that build in higher binding affinities, and simple chemistries to
> pattern recognition ligands onto chips are needed. In addition,
> advances in reactive chemistries to improve binding of these ligands
> to the array matrix, as well as the development of modified or
> synthetic ligands to improve the stability of ligands (to permit reuse
> of arrays, for example) would make these techniques more robust. In
> addition, construction of hybrid organic sol-gel materials or modified
> semiconductor materials (e.g., Nanogen's chip technology) may provide
> rapid, more reproducible fabrication methods. There are also issues
> concerning cost and quality control to be addressed before this
> technology can be broadly applied to the biothreat problem.
>
> Next-generation microarray technology likely will involve the
> elimination of confocal optical techniques for readout and will,
> rather, integrate the molecular interactions with signal transduction
> at the silicon surface, or in thin film composites. Current directions
> in BES Nanoscience and Technology are already producing prototype
> devices demonstrating what might be possible.
>
> *Single Molecule DNA Sequencing.* The possibility of sequencing single
> molecules of DNA at kilohertz rates using nanotechnologies would be
> essential for real-time, high-sensitivity identification of pathogens
> or real-time DNA fingerprinting of individuals at portals. One
> approach to the sequencing of single polynucleotide molecules is to
> use conductance probes within a molecular-scale aperture. There have
> recently been intriguing suggestions about how one might rapidly
> determine the sequence of a single DNA molecule contained in a buffer
> solution by transporting it through a voltage-biased nanoscale
> aperture while monitoring the ionic current through that
> aperture.^31,32^
>
> Fundamental research issues are to develop fabrication strategies for
> forming nanometer-scale structures, understand limits to dimensional
> stability and surface roughness, evaluate transport for solvated ions
> and polyelectrolytes in confined fluids, investigate polymer dynamics
> in confined spaces, and interface nanostructured material to the
> "real-world." These investigations should be pursued both
> experimentally and theoretically.

## Medical Diagnostics 

  ----------------------------------- -----------------------------------
  **Technology Need**                 **Present Problem**

  Rapid diagnosis of infection or     Clinical diagnosis is too slow for
  detection of human exposure.        effective early treatment
                                      approaches.

  Diagnostic tools for use in         Instruments need to become simpler,
  point-of-care facilities.           less expensive, and able to operate
                                      after prolonged storage times.
  ----------------------------------- -----------------------------------

In the event of a bioterrorist attack, it will be essential to have
technologies that can be used to rapidly detect infection from, or
exposure to, biothreat agents within potentially large human
populations. Early diagnosis of infection or detection of exposure can
make all the difference in successfully treating victims and in
minimizing the impact to the local medical community. For example, if
intoxication by botulinum neurotoxin (BoNT) can be detected prior to
clinical diagnosis, this disease can be effectively treated with
therapeutic antibodies; if not, the only recourse is respiratory aid for
6--8 weeks in an intensive care unit.^33^ Even a limited terrorist
attack with BoNT could paralyze the medical community. Medical diagnosis
will, most likely, take place in a doctor\'s office or point-of-care
facility. Given the expected low incidence of events, diagnostic
instrumentation or sensors will be used sparingly, if at all, to address
biothreat attacks. Accordingly, it is critical that they have dual use
capabilities and be used regularly to address common infectious disease,
or they are likely to be ineffective in the event of a real biothreat
attack.^34^ Other attributes, such as cost, speed, and simplicity of use
are also important. The most important contributions of BES are likely
to come from the preparation and characterization of novel materials for
new diagnostic or therapeutic devices, from the development of new tools
for diagnosis and the development and application of new materials and
tools to study host-pathogen interactions at a fundamental level.

#### Bio-Compatible Materials for Therapeutic and Diagnostic Applications {#bio-compatible-materials-for-therapeutic-and-diagnostic-applications .unnumbered}

New bio-compatible materials are need for a variety of biomedical
applications encompassing diagnosis and treatment. These include
optoelectronic materials that have ideal light-emitting characteristics
for probing biological systems. The ability to implant macro- and
nano-structured materials for detecting disease, monitoring exposure,
and therapy after exposure is also an area to explore.

#### New Materials for Diagnostic Devices {#new-materials-for-diagnostic-devices .unnumbered}

This area of research seeks to apply materials (self-assembled,
semiconductor, glass, and polymer) science and technology toward early
detection of infection by biomedical analysis of blood, body fluids, and
tissues in real time at a point-of-care setting. Such detection includes
measuring the response of the human immune system to invading viral and
bacterial pathogens as well as detecting markers of the pathogens
themselves. Important candidate technologies include novel
microfabricated and nanofabricated structures and devices that are
integrated with cells, microorganisms, or biomolecules for analysis,
separation, or processing. They exploit the interplay of the
microfabricated structure/device materials and architectures with the
biosystem by interrogating the biophysical or biochemical properties of
bioparticles. Such materials may be used for in vitro detection, in
noninvasive monitoring as in ex vivo detectors and dermal contact
sensors, or in vivo for detection, imaging, and therapy.^35^

Microfabricated and nanofabricated materials for
optical-electrical-mechanical systems enable characterization techniques
that offer higher speed, sensitivity, and efficiency over conventional
methods. Such structures or devices could include microfabricated flow
structures; micro-cytometers for cell analysis, identification, and
sorting; DNA, RNA, and protein sequencing; insulin or glucose detectors;
antibody and virus detectors.^36^

This area will need modeling and simulation to better understand and
predict the material or biosystem interactions at micro- or nano-meter
scales. Examples include the studies of the surface modification of
semiconductors and biocompatible materials (semiconductors, glasses, and
polymers) integrated at the wafer level (lab on a chip), optical
microcavities or porous fabricated materials containing biological
fluids under analysis or modification by enhanced physical or chemical
effects, and micromanipulation of molecules/cells/particulates by
microfabricated devices. Also included are nanostructured surfaces that
exploit enhanced surface effects to study, modify, or manipulate cells,
molecules, or particulates; surface-enhanced phenomena arising from
direct contact of biosystems with materials; biomimetic materials such
as membrane mimetic architectures; and hybrid organic-inorganic
materials.

It is evident that the research opportunities include a broad range of
materials science such as self-assembled and hybrid materials,
semiconductors (silicon, III-Vs, and other compounds) insulators
(glasses, dielectrics, fibers), and organics (polymers). The essential
focus is on understanding and making very small structures and devices
from these materials and applying them to the flow, capture, detection,
or processing of biological species. Novel theories of
substrate-organism interactions, experimental techniques, fundamental
materials science, and materials processing are all included.

#### Spectromicroscopic Imaging at Molecular and Cellular Levels {#spectromicroscopic-imaging-at-molecular-and-cellular-levels .unnumbered}

Imaging technologies have experienced great advances in recent years,
and their use in biology has been increasingly exploited for both
research and medical diagnostics. The traditional imaging techniques
such as MRI and CT, for example, can generate highly detailed spatial
images, but the observed contrast does not directly contain useful
biochemical information. If one could obtain a *biomolecular image* of
tissues or cells, it would be possible to discern the structurally
specific chemical basis of dynamic biological processes or take
advantage of the combination of shape and unique chemical composition of
individual cells to obtain fingerprint signatures, including diseased
cells and pathogenic bacteria, without the addition of dyes or labels.
Vibrational imaging technologies that correlate molecular spectral
(intensity as a function of energy) data with spatial variables can
provide such a molecular map. The primary challenges to the development
of this approach include needed improvements in the sensitive detection
of vibrational images and development of image understanding tools to
extract relevant information. These problems may be addressed using
infrared and coherent anti-stokes Raman (CARS) methods as outlined
below.^37^

#### FTIR Detection of Pathogens in Cells {#ftir-detection-of-pathogens-in-cells .unnumbered}

Fourier transform infrared (FTIR) spectromicroscopy is a technology that
may be enabling for new detection techniques for pathogens in infected
cells, as well as in the environment.^38^ FTIR has the advantage of a
wide spectrum, very bright beam that can interrogate surfaces with
living intact cells. It has been recently demonstrated that
high-brightness synchrotron radiation-FTIR (SR-FTIR) spectromicroscopy
with a spatial resolution of less than 10 um has the ability to detect
many biochemical changes, such as different phases of the cell cycle and
exposure to very dilute chemical agents (e.g., 10^-11^ M of dioxin).^39^
It also allows one to use the beam to study localized cellular
processes. This research also indicates that synchrotron infrared
photons do not induce detectable intracellular chemistry changes or
physiological effects (long term or short term) on cells that are
exposed to the synchrotron infrared beam. The reflected spectra can show
unique responses in particular wavelengths that indicate compounds or
suites of compounds that are unique to that organism or indicate
metabolic/biochemical changes that have occurred in a host cell in
response to infection or toxicity. FTIR spectromicroscopy is sensitive
enough to detect reproducibly distinct (spectral) changes in a single
hydrated and living fibroblast (lung) cell as the cell undergoes
different stages of its cell cycle. Thus, sputum samples from exposed
individuals could be examined to determine if they have been infected,
prior to showing any symptoms. In addition, the spectra from
environmental samples have been used to identify bacteria on
environmental surfaces and demonstrate their juxtaposition to
substrates. Once the spectra that are critical have been identified,
then a small tuned laser system that might even be handheld would enable
rapid field detection both by first responders and clinicians.

#### *IR Focal Plane Arrays for Hyperspectral Imaging* {#ir-focal-plane-arrays-for-hyperspectral-imaging .unnumbered}

SR-FTIR shows great promise as a research tool to further unravel what
can be learned about disease using spectromicoscopy techniques. It is
not, however, practical to rely on limited high-brightness sources for
rapid diagnosis that will be needed in the event of a terrorist attack.
For this reason, it is important to continue to develop more flexible
approaches based on advanced detector systems and more conventional
sources that could be deployed in a doctor\'s office. The recent
deployment of multichannel 2-D focal plane array (FPA) detectors
including InSb, HgCdTe (MCT), and quantum-well infrared photoconductors
(QWIP) on the infrared microscope has facilitated the application of
hyperspectral imaging to vibrational microspectroscopy. These
array-based technologies are being actively developed, with sensitivity
and spatial resolution issues still to be fully characterized and
optimized.

#### *Coherent Anti-Stokes Raman Scattering (CARS)* {#coherent-anti-stokes-raman-scattering-cars .unnumbered}

Recently, nonlinear multiphoton techniques have been applied to
fluorescence imaging. In these experiments, femtosecond pulses of
near-infrared light are tightly focused on the sample. Two-photon
absorption will occur only from within the focal volume where the light
intensity is high; hence, fluorescence originates only from the focal
volume. Similarly, nonlinear optical techniques for vibrational
spectroscopy have many benefits for chemical imaging. CARS is a
nonlinear Raman technique that produces coherent emission of Raman
radiation.^37^ The primary value of CARS includes its superior
resolution capability (sub-diffraction) and, as a stimulated process,
its high signal levels. Even more important is the fact that it does not
require dye-labeling as do may fluorescent probe methods. Molecule
specific imaging is possible in unmodified cells or tissues, greatly
simplifying sample preparation and other issues related to medical
applications of laser based imaging methods.

#### Image Understanding {#image-understanding .unnumbered}

While vibrational spectroscopy can provide chemical information for all
species present, the sheer volume of information generated can make data
analysis problematic. As each chemical species gives rise to many
vibrational modes, the measured spectrum will be comprised of
contributions from all of these. A similar problem has already been
successfully addressed using an alternate technique based on
"evolutionary algorithms." The macroscopic applications of astronomy and
satellite-based surveillance systems have made use of hyperspectral
imaging, and the data analysis routines used in these disciplines have
attained fairly high levels of sophistication. Two approaches, both
separately and in combination, will improve the utility of vibrational
images: (1) genetic learning algorithms that use a library of signatures
and user-selected screening algorithms to categorize individual and
combined elements within an image and (2) the application of a
multiscale, multiresolution algorithms to both compress and optimally
select the discriminating characteristics of vibrational images.

The realistic potential for correlating molecular images of cells to
disease states offers enormous technical benefits, which would accrue
from better understanding the relevant biochemical foundations of
cellular responses. In both the biological and the materials science
arenas, the instrumentation and analysis techniques proposed here will
yield information with an unprecedented level of spatial and chemical
detail, and ultimately allow the examination of how heterogeneous
molecular-level structure influences and controls macroscopic function.

#### *New Materials and Tools to Study Host Pathogen Interactions* {#new-materials-and-tools-to-study-host-pathogen-interactions .unnumbered}

An understanding of how pathogens invade the host can help guide the
development of both diagnostic and therapeutic tools. One example is the
mechanisms of cellular invasion of viruses and bacterial protein toxins.
In both cases, the cellular invasion mechanism always involves pathogen
recognition of multiple receptors on the surface of targeted cells. A
clear understanding of the ligand-receptor interactions can be used to
design man-made receptors that bind the active receptor site of the
pathogen more tightly than the natural receptors. These man-made
receptors can then be used for inhibition to block the pathogen\'s
invasion of cells or as recognition molecules for sensitive detection of
the pathogen. Structural biology (neutron and x-ray diffraction as well
as electron microscopy) can be used to clarify the receptor binding
sites to guide the synthesis of man-made receptors with high binding
affinities.^40^

The mechanisms of translocation of a bacterial toxin or viral particle
(or its genetic information and core proteins) across the cell membrane
is understood for only a limited number of pathogens. Often, the
pathogen-receptor complex further aggregates on the surface of the cell
membrane, resulting in structural changes that open a channel for
translocation of, for example, the enzymatic subunit of a protein toxin.
Understanding the detailed invasion mechanism could provide the insight
to develop entirely new ways to detect and treat. In this case, new
membrane mimetic architectures and research tools that can be used to
directly study the invasion mechanisms would help to develop that
understanding. For example, the use of neutron or x-ray reflectometry
and low angle diffraction to study protein toxins interacting with
natural receptors at the surface of a fluid phospholipid bilayers could
help in developing a more detailed understanding of host-pathogen
interactions.^41^ There are a number if other imaging (e.g., scanning
probe microscopy^42^ and various electron microscopies) and
spectroscopic techniques (above) that could also shed light on
host-pathogen interactions. Single molecule spectroscopic and imaging
methods have recently been developed that allow real-time imaging of the
entire process of viral attack, invasion, and control, providing
valuable kinetic data as a complement to these structural studies of the
mechanism.

#### *Synthesis and Study of Molecular Prophylactics and Therapeutics* {#synthesis-and-study-of-molecular-prophylactics-and-therapeutics .unnumbered}

Materials with molecular recognition moieties that are attached to
carrier vehicles could provide excellent drug delivery systems for
pathogens either in vivo as a therapeutic or in solution as a
decontaminant.^43^ These same materials could also be used to detect and
image disease by incorporating imaging molecules or materials (e.g.,
radionuclides and magnetic or fluorescent molecules). Functionalized
polymers and self-assembled structures (e.g., liposomes, liposome-coated
particles, micelles, dendrimers, and cage structures) have the
properties to physically and/or chemically carry therapeutic agents to
the pathogen. Cell or tissue-targeting molecules attached to these or
other materials could offer the targeting as well as release mechanism
for drug delivery. It has recently been possible to select peptides and
single chain antibodies that both target specific cell/tissue types and
also effect the translocation of phage particles across the cell
membrane. These molecules are obtained using phage display methods where
the selection pressure requires both recognition and endocytosis and are
remarkable in their specificity in targeting specific cell or tissue
types and in being able to distinguish between healthy and sick cells.
Schemes to link these cell/tissue targeting molecules with the drug
delivery particles must also be further developed. Moreover, these
hybrid materials that couple cell/tissue targeting molecules with drug-,
gene-, or imaging- containing particles must be made to be stealthy in
the vascular system. In the future, it may also be possible to design
and fabricate nano-structured hybrid materials where highly specific
recognition events between the cell/tissue targeting molecules and the
targeted cells/tissues triggers the generation of a measurable signal or
the activation and release of therapeutic agents.

Synthetic agents that can neutralize the pathogen by mimicking the
target receptor or docking area at the cell surface could significantly
reduce the risk of infection. To address this area, an in-depth
understanding of the modus operandi of the pathogen must be addressed.
Structural analyses of biotoxins, viral particles, and organisms on
lipid membranes should be probed at the nanoscale and in real time.
Techniques of relevant use include scanning probes, neutron and light
scattering, and modeling simulations. By thoroughly characterizing the
path of pathogen attack, weaknesses in its cell invasive mechanism will
become clear. Through this effort, small molecule reagents could be
developed to attack the pathogen during its cellular invasion, as well
as decoys prepared with cell surface mimics.

### Protection 

  ----------------------------------- -----------------------------------
  **Technology Need**                 **Present Problem**

  Protect people, animals, crops and  Current approaches not able to meet
  living spaces..                     practical needs of large
                                      populations and indoor spaces.
  ----------------------------------- -----------------------------------

Devices and systems are required to protect at-risk people, animals,
crops, and material from the adverse impacts associated with biological
threat agents. The need to protect-to-warn to facilitate protection of
people is discussed in previous sections. The risk of infectious disease
also extends to animals (e.g., impact on security dogs employed to
protect facilities) and materials (e.g., microorganisms released into
fuel storage systems can cause significant adverse impacts).

Functional devices are available to remove biological threat agents from
air and water, and the agents can be killed in foods. However, the
current protective equipment suffers from significant practical
limitations, in particular for protection of large populations and
indoor spaces. Limitations are associated with excessive unit costs
(e.g., high efficiency particulate filters), operational costs (e.g.,
fitting and certification of respirators), and impairment of function
(e.g., respiratory burden of negative pressure protective masks).
Aspects of the critical infrastructure are at risk from microorganisms
that can degrade or interfere with industrial and other large-scale
processes (e.g., fuel storage).

Research has been conducted to incrementally improve protective
equipment along traditional lines of inquiry. However, advances in BES
areas of research suggest great advances in protective equipment can be
realized as described below.

#### Individual Protection {#individual-protection .unnumbered}

There is a clear need for advanced materials from which to construct
next-generation personnel protection equipment (PPE). For example,
considerable waste could be eliminated by designing HEPA filter
canisters that contain a color indicator to indicate when the filter has
reached a conservative limit of capacity upon exposure to biological
(and chemical) agents. Such an indicator could also provide the user
with an additional degree of confidence that the filter was performing
its function. The indicator would preferably be a colorimetric scheme
(e.g., blue to red) that allows a distinct and rapid assessment of the
material's state. The color-change mechanism should be linked to a
specific chemical recognition scheme that is activated at a threshold
value. More than one color-changing material specific to different
agents could be incorporated into the filters to provide additional
information to the user about the environment he was exposed to.

New materials for protective outer garments are especially needed. Even
the more durable military garments must be discarded after exposure to
agents, as there is no means of assessing the remaining protective
capacity of the suits (short of sensory detection of the suit no longer
functioning!). SBCCOM is already investigating membrane technologies for
the next-generation JSLIST suit, and DOE's materials research programs
could accelerate this development through the development of specialized
polymers, as well as coating fabrics or other textiles with reactive
surfaces of either chemical or enzymatic nature that could detoxify CB
agents on contact (e.g., Tiller et al. at MIT recently reported that
certain polymers, such as HexylPVP, can kill 95% of bacteria on
contact). Materials that can enzymatically cleave amide bonds could
neutralize the majority of biotoxins by degrading them to small inactive
pieces. Studies of the surface structure of whole organisms or viral
particles, on the other hand, could provide insights into means of
inactivating pathogens using unique chemistries or materials to
inactivate them via cross linking or synthetic enzymatic processes that
change the organism/particle coat characteristics.

#### Collective Protection {#collective-protection .unnumbered}

The terrorist dispersal of *B. anthracis* spores through the U.S. mail
system, contaminating USPS facilities, the Hart Senate Office Building,
and other buildings through which the mail passed and was opened,
revealed a new mode for deployment of biological agents. HVAC systems as
currently designed also make it difficult to prevent re-aerosolization
of settled agent, and hinder decontamination efforts. Immediate measures
have been taken to decontaminate mail, and mail handlers have been
advised to scrutinize mail for indications that might suggest suspicious
contents. These measures are clearly reactionary, and active measures to
detect and prevent the spread of biological contamination are necessary.
Such protective measures would also be applicable to transportable
shelters and mobile platforms.

Respiratory protection, as described above, is largely accomplished
through the use of HEPA filtration given current technology. In the case
of buildings, new approaches to air filtration, from the design of more
effective air handling and prefilters, to advanced materials to increase
the duty cycle and durability of the filter matrix are necessary.
Selective filtration materials may be desirable to control influent air,
along with recirculation within a building or work area. Such materials
could also find use in the physical handling of mail and packages to
provide worker protection. The use of novel reactive or absorptive
materials that would inactivate any biological agent on contact would
represent a quantum leap over current technology. These materials would
also have the collateral benefit of providing solutions to so-called
"sick building syndrome," which is caused by a variety of fungi,
especially *Stachybotris spp*. This problem is so endemic and difficult
to combat in the U.S. that many homeowners' insurance policies
specifically exclude coverage for this problem. This also represents a
significant component of the problem in the workplace.

### Decontamination and Remediation

  ----------------------------------- -----------------------------------
  **Technology Need**                 **Present Problem**

  Biological decontamination of       Need to develop decontamination
  people, surfaces, and buildings.    approaches that are effective,
                                      efficient, environmentally benign,
                                      and not harmful to humans or
                                      materials.
  ----------------------------------- -----------------------------------

In the event of a release of biothreat agents, decontamination of
people, surfaces, and spaces will be required to facilitate crisis
response and consequence management. Decontamination will limit spread
of the biohazard and facilitate prompt medical treatment to save lives.
Following resolution of the incident, remediation of residual hazards
will be required to return property, equipment, and personal belongings,
at an acceptable level of risk, to owners.

Operational requirements for decontamination and remediation are
associated with identification and quantification of hazard levels, and
removal and/or killing of microorganisms. Biological threat agents
(e.g., spores and some viruses) can be extremely stable in the
environment, and contamination may be widespread and of low
concentration. In addition, microorganisms may be stabilized against
environmental stresses to enhance their effectiveness. Development of
reactive chemicals and materials that kill microorganisms and have
acceptable levels of environmental, health, and material risk has not
been achieved.

Spaces to be decontaminated/sterilized range from large outdoor and
indoor areas to complicated building ventilation systems. Materials
requiring treatment range from construction materials to high-value art
work (e.g., Senate Hart Building). Contaminated and infected people pose
additional challenges. Current decontamination and sterilization agents
and application equipment do not provide effective, efficient, and
environmentally benign decontamination and remediation capabilities to
address biothreats.

Fundamental scientific issues must be pursued to develop required
capabilities described above. Research needs reside within many of the
focus areas of the BES program. Of principal interest are scientific
advances that will allow large-scale inexpensive production of effective
materials that are highly specific in their destruction of
microorganisms. Potential methods for the decontamination of sensitive
equipment and valuable art include supercritical CO~2~, environmentally
friendly solvent wash systems, thermal approaches, and plasma
approaches. For ductwork and other "hard to reach" places, methods to
vaporize or encapsulate existing or newly developed noncorrosive
chemistries or the development or identification of noncorrosive gases
is needed. These chemistries may be agent-specific, since the primary
use would be for facility restoration. Methods could be developed for
deactivation and destruction of agents rapidly by solid matrices for
remediation of bulk agents. This could include methods such as reactive
nanoparticles, reactive microparticles, adsorption, and highly reactive
surface chemistries.

#### Encapsulating Materials {#encapsulating-materials .unnumbered}

Many objects that may be contaminated like desktops, chairs, large
machines (e.g., letter sorters, etc.), and fixed equipment are too large
to be quickly and efficiently decontaminated. In addition, many biocides
may also be toxic or have damaging effects on objects being treated
(e.g., oxidation, depolymerization, etc.). Thus, a simple inert material
that can quickly and fully encapsulate an object to contain a diverse
array of biological threats is highly desirable. The problem with many
current materials like polyurethane foam is that they are too porous to
be effective in containing spores. The ideal encapsulating material
would be inert, transparent, thin, resilient to normal handling, applied
as an aerosol, and easily applied by a first responder. Plastics and
polymers research will find application in this area.

#### Irradiation {#irradiation .unnumbered}

Microwave irradiation would become a viable technique for destroying
*Bacillus anthracis* or other bacterial spores if the spores were found
to have absorption lines in the few GHz region. Such specific absorption
lines would then couple power into the spore, in analogy with the 2.45
GHz line of water exploited in microwave cooking. Research is required
to determine if bacterial spores do have such absorption bands. If this
were the case, then radio frequency (RF) power sources with relatively
low powers of about 10 kW could potentially provide an effective method
for selectively destroying bacterial spores.

In the case of a federal need for sterilization of a significant mail
stream using electron irradiation, BES research expertise in the design
of specialized linear accelerators could be brought to bear on this
problem. There are a number of approaches, requiring R&D, that could
provide sources superior to those presently available including, for
example, (1) an integrated sheet-beam-klystron and linac that would
provide a very compact device using sheet electron beam technology to
spread the energy dissipation over larger areas than a conventional
round beam, thus allowing higher average powers to be reached before
destruction of the irradiated mail and (2) magnetron driven systems that
would result in low-cost, very robust linear accelerators suitable for
widespread deployment.

#### Nanoparticle Fluorescence {#nanoparticle-fluorescence .unnumbered}

High affinity ligands, with an attached reporter, in a nano-material
structure may be used for identification of surface contamination to
guide decontamination treatment. Success of this effort will require
directed synthesis of highly specific binding agents, which are attached
to nano-structures. The process must be amenable to large-quantity,
low-cost manufacturing.

#### Laser-Induced Fluorescence from Semiconductor Nanoparticles {#laser-induced-fluorescence-from-semiconductor-nanoparticles .unnumbered}

This area of research encompasses surface functionalized semiconductor
quantum dot particles equipped with specified bulk optical properties
for interacting with external electromagnetic fields generated by
lasers. The surfaces are functionalized for selective binding to cell
membranes or pathogens.^44^ One use of these luminescent semiconductor
nanoparticles is to label cell membranes, organelles, or cytoplasmic
molecules for the purpose of imaging the cell structure. They have
advantages over conventional fluorescent molecular probes, including
ease of synthesis, broadband absorption, narrowband emission, and
wavelength selection by quantum size effects.^45,46^ An array of such
nanoparticles tailored to emit at selected discrete wavelengths can be
used to identify pathogens, for example, in microfluidic systems in real
time in a field setting for evaluating residual agent levels and hence
risk.

#### Reactive Chemistry {#reactive-chemistry .unnumbered}

Develop noncorrosive, materials compatible, nontoxic, and
environmentally friendly oxidative or enzymatic chemical and biological
decontaminants (both aqueous and nonaqueous) to replace current toxic
and corrosive formulations for use in first response and facility
restoration. These formulations should be capable of neutralizing CBW
agents at material-friendly pH of 7.5--9.5 by either oxidation or
displacement reactions yielding acceptable reaction products. The
decontaminants should be effective against standard CBW agents, TICs,
and TIMs, and other biological pathogens. Formulations should be
inexpensive and easily deployable in the field.

#### Agent Targeted Remediation {#agent-targeted-remediation .unnumbered}

Advances in ligand design and synthesis, when combined with reactive
chemistries and novel materials hold the potential for development of
decontamination systems that are selectively targeted at biological
threat agents and that can self-activate upon recognition of the target
substrate. Development of this capability would require
interdisciplinary basic research and cross-functional coordination
between researchers engaged in ligand and decontaminant development.
Bacterial chemotaxis is an example of a simple chemoreceptor system that
directly activates a response. A molecular system that contains a
specific receptor that then activates the release of a biocide is an
exciting possibility and within the realm of the Nanoscience and
Nanotechnology programs.

## Research Needs

A number of themes that emerged from the discussion of scientific issues
and opportunities build on the areas of strength in the BES research
program.

### Scientific Issues

#### Molecular Recognition {#molecular-recognition .unnumbered}

Molecular recognition is an underlying research theme for almost every
aspect of biothreat reduction discussed. There are research needs for
ligand design in terms of specificity, desired affinities and kinetics
of binding, robustness, and manufacturability. Biological and abiotic
ligands are relevant. The structural biology of receptors and complexes
with receptors will be important in detection and in therapies designed
to block infection by mimicking key receptors required for pathogen
invasion and proliferation.

#### Integrated Molecular Systems {#integrated-molecular-systems .unnumbered}

Sensing biological agents and medical diagnostics depend upon being able
to integrate recognition with signaling and amplification. Technologies
for detecting small toxins such as aflatoxin and small peptides are
needed.

#### Interfacial Science {#interfacial-science-1 .unnumbered}

Like molecular recognition, interfacial science is an underlying theme
of every aspect of biothreat reduction. Nano-bio interfaces, transport
at interfaces, functional interfaces through the attachment of
recognition molecules, stability of layered materials (phase control,
adhesion), and transport and fate of pathogens in the environment all
depend on understanding and advances in interfacial science.

#### Novel Materials {#novel-materials-2 .unnumbered}

New materials with novel properties are needed for detection,
diagnostics, protection, decontamination, and remediation. Nano-bio
materials, hybrid materials and systems, self-organized materials,
patterned surfaces, reactive materials, molecular electronics will all
be important.

#### Nanoscience and Technology {#nanoscience-and-technology .unnumbered}

Detection, diagnostic, decontamination, and remediation technologies
that build upon the principles of molecular recognition, signaling, and
amplification require tools for studying nanostructures and
nanostructured materials,

#### Spectroscopy {#spectroscopy .unnumbered}

Spectroscopic tools will be needed as sensitive, specific probes of
molecular and nano-scale structures, for probing interfacial phenomena,
as stand-off detection systems, for sensing, for single particle
analysis, etc.

#### Computing, Modeling, and Simulation {#computing-modeling-and-simulation-1 .unnumbered}

Molecular dynamics simulations will be important for understanding
recognition, collective phenomena, materials properties, and interfacial
interactions. High-speed data analysis is important for analyzing array
data, data from distributed sensors or trigger systems. Intelligent
control systems to coordinate multiple components of integrated sensor
systems or networks of sensors will be important to efficient operation
of complex systems triggered by sentinel detectors, and to
interpretation of responses from multiple sensors.

#### Advanced Instrumentation {#advanced-instrumentation .unnumbered}

New advanced instrumentation is needed for materials and interfacial
characterizations, high-resolution bio-imaging, mass spectrometry
(precision, portable, high-mass analysis), and stand-off detection using
laser systems, spectroscopy, or hyperspectral imaging.

#### Integrated Devices {#integrated-devices .unnumbered}

Integrated devices require research and development in microfluidics and
nanofluidics, optoelectronics, microelectronics, MEMS, and a wide range
of functional materials. Achieving these integration goals will require
new experimental tools and modeling approaches that are able to address
materials interfaces, energy and information transfer, device
manufacturing, and materials assembly.

### Research Environment and Infrastructure Requirements 

Addressing the R&D needs of such a complex problem as biothreat
reduction requires an unusual hybrid environment that includes elements
from both academic, industry, and defense-related research environments.
For example, the best scientists and technologists must be attracted;
there must be mechanisms to support large, cross-disciplinary teams from
across the community; and major facilities for molecular and materials
characterization are needed in a research environment that is juxtaposed
with secure environments. Specific to countering the biological
terrorist threat is the need for a biology expertise that can interact
with physical and chemical sciences as well as engineering and
computational science.

#### Special Facilities and Large-Scale User Facilities {#special-facilities-and-large-scale-user-facilities .unnumbered}

Synchrotron and neutron scattering facilities will be needed for
materials characterization and structural biology. State-of-the-art
macromolecular crystallography that can be carried out possibly in a
secure location or with Biosafety Level 3 (BSL-3) capabilities might be
an asset to consider at one of the synchrotron facilities. A "biosurety"
program and specialized facilities for handling pathogens, such as
Biological Safety level-2 and -3 laboratories are critical. All of these
elements are contained within the DOE complex of national laboratories.
Mechanisms should be put in place to make the appropriate facilities
available these teams of research scientists and engineers.

#### Nanoscale Science Research Centers {#nanoscale-science-research-centers .unnumbered}

Facilities for nanoscience and technology, including fabrication, will
be key for many aspects of biothreat reduction. The Nanoscale Science
Research Centers will also be centers of excellence for interfacial
science, synthesis of nanomaterials, self-assembly, novel materials,
biomimetics, and more.

### Relationships with Other Programs

The DOE Basic Energy Science program is partnered with other major
programs that bring critical expertise to the problem of reducing the
threat from bioterrorism. For example, there are programs in
Environmental Management (EM), Super Computing (ASCR), and Biological
and Environmental Research (BER). In particular, a partnership with the
BER and its genomic science capabilities will be a critical. Through the
Joint Genome Institute, the department has highly competitive genomic
sequencing capabilities in terms of both cost and throughput. These
sequencing capabilities can provide a wealth of information on human,
plant, and animal pathogens and the host systems they attack. The
BER/ASCR initiative, Genomes to Life, explicitly targets genome scale
analyses that will yield systems-level information on the composition
and function of the biochemical components, networks, and pathways that
carry out the fundamental processes governing life. The initiative will
also develop the computational tools and infrastructure for integrating
and understanding the vast amount of data that will be generated and
then used to gain predictive understanding of the fundamental processes
in biology. This initiative promises to be a rich source of information
on protein complexes, regulatory networks, and microbial communities
that will significantly enhance the potential for success in the
material and chemical science programs within BES efforts that will
focus on specific bio-molecular assemblies and interfacial systems for
biothreat reduction technologies. The BER program in climate modeling
and atmospherics is also an important potential partner in the race to
develop the best defense technologies against biothreats.

The NNSA, within DOE, can be a powerful ally with BES in the fight
against bio-terrorism. The mission of the NNSA's Chemical and Biological
National Security Program (CBNP) is to develop, demonstrate, and deliver
technologies and systems that will help the nation prepare for,
recognize, and respond to chemical or biological attacks on the civilian
population. The focus of this program is on developing new technologies
that can be deployed on a 3--5 year time scale. In addition, the NNSA's
nonproliferation mission has been expanded explicitly to include
chemical and biological weapons of mass destruction. The longer term R&D
focus of BES, and BER, will be important fuel for CBNP's future
generations of technology development.

It will be key for DOE to develop strategic alliances with other offices
or agencies with expertise and research and development capabilities for
different aspects of anti-bioterrorism. Perhaps most importantly among
these will be the Health and Human Services' National Institutes of
Health (NIH) and Centers for Disease Control and Prevention (CDC), the
Department of Defense, and the Department of Agriculture. Some
interactions have already formed and only need to be strengthened and
solidified. It will also be key to interface with the ultimate users of
the technologies being developed in order to understand the operational
needs, such as first responders, public health, Department of
Transportation, Immigration and Naturalization, military, and law
enforcement.

### Dual-Use Opportunities

The detection, identification, medical diagnostics, and clean up
capabilities needed to protect our citizens against the bio-terrorist
threat will also serve to strengthen our public health infrastructure in
general and provide increased protection against naturally emerging
infectious diseases. Also, the application of these technologies to
agricultural threats will aid in protecting our food supplies and ensure
its safety.

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# Workshop Conclusions and Recommendations

The goal of this workshop was to identify the critical scientific issues
and opportunities where basic research supported by the Department of
Energy (DOE) Office of Basic Energy Sciences can have an impact on our
nation's ability to counter terrorism. The two days of workshop
presentations and discussions clearly showed how many of the research
directions currently supported by BES are either currently having an
impact or may potentially have a direct impact on important technology
needs for countering terrorism. In addition, the facilities and
scientific capabilities that BES supports at the DOE national
laboratories and universities were identified as having extremely high
value to our nation's war on terrorism. It was concluded that the DOE
national laboratories and the BES special and user facilities can be
expected to play a continued and increasing role in our nation's efforts
to counter terrorism.

In this final section of the report, we turned to the advice provided by
our plenary speakers to develop a set of recommendations that will help
BES and other basic research organizations further increase the impact
of its research capabilities on problems associated with countering
terrorism.

-   [Invest Strategically]{.underline} -- Here, we focus on
    ***Cross-Cutting Research*** that has the potential to have an
    impact on a broad set of technology needs, thereby providing the
    greatest return on the research investment.

-   [Build Team Efforts]{.underline} -- We addressed team efforts in two
    contexts: (1) ***Research Environments and Infrastructures*** that
    encourage and enable cross-disciplinary science and technology teams
    to explore and integrate new scientific discoveries and (2)
    Exploring ***Relationships with Other Programs*** that will build
    connections between scientific advances and those groups responsible
    for technology development and implementation.

-   [Consider Dual Use]{.underline} -- We have identified areas of
    research that present significant ***Dual-Use Opportunities*** for
    application to countering terrorism and other complementary
    technology needs.

## Cross-Cutting Research

Sections 2--4 of this report provide detailed descriptions of critical
scientific issues and their relevance to technology needs associated
with Radiological and Nuclear, Chemical, and Biological threats. From
these underlying scientific issues, a number of cross-cutting research
themes emerged.

**[Recommendation]{.underline}:** *We recommend continued or increased
funding for the following research directions since they underpin many
technologies that have high probability to impact our nation's ability
to counter terrorism.*

> ***Novel Materials*** -- A wide range of new and nanophase materials
> will be needed as catalysts, sensors, semiconductor detectors and
> solid-state lasers, membranes, lightweight structures, and molecular
> electronic and optical materials. Capabilities are needed in synthesis
> and characterization of self- and directed assembly, nano-bio hybrids,
> complex functional materials, and patterned and templated surfaces.
> Characterization will require a suite of tools ranging from large
> user-based x-ray and neutron scattering facilities to novel local
> probes. The materials development will require an underpinning in
> predictive modeling and theory.
>
> ***Interfacial Chemistry*** -- Fundamental theoretical and
> experimental tools and models to probe molecular interactions with
> solid/vapor and solid/liquid interfaces will be critical to
> development of new selective sensors, transport and fate models,
> development of improved separations chemistry, and development of new
> protective barrier and catalytic materials for protective clothing and
> toxin neutralization. Research challenges include development of
> accurate thermodynamic and kinetic models for interfacial behavior and
> ultra-fast local probes to study interfacial molecular interactions.
>
> ***Chemical and Molecular Recognition*** -- Molecule/ion selective
> receptors could have an impact on a wide range of detection,
> protection, and response technology needs. Progress will require the
> development and application of new theoretical and experimental tools
> as well as new combinations of tools and expertise spanning physics,
> chemistry, and biology. It will be important to develop integrated
> receptors that provide pathways for transducing recognition events to
> surrounding structures and devices.
>
> ***Laser and Mass Spectroscopy*** -- Laser spectroscopy is expected to
> play a key role in stand-off detection and integrated systems.
> Research needs include new, compact, solid-state laser sources,
> semiconductor/biological interfaces, luminescent nanoparticles, and
> improved data analysis and data mining algorithms. Mass spectroscopy
> offers the ultimate in specific recognition, but investment is needed
> to develop more compact and portable approaches.
>
> ***Nanoscale Science--*** Many critical scientific issues and
> challenges associated with each threat area are rooted at the
> nanoscale behavior of materials and interfaces. New tools for
> fabricating nanoscale structures, probing structure and properties at
> the nanoscale, modeling properties and behavior, and integrating
> across multiple-length scales will be needed. The Nanoscale Science
> Research Centers being developed by BES can play a critical role in
> providing the tools and research environment needed to address these
> critical problems.
>
> ***Miniaturized Integrated Systems --*** Miniaturization and
> integration research themes underlie future ability to develop
> inexpensive and reliable devices for first responders. Critical
> research issues include microfluid and nanofluid transport, surface
> treatment and functionalization, combination of top-down and bottom-up
> fabrication techniques, and coupling of nanoscale and continuum models
> for mass and energy transport.
>
> ***Computing, Modeling, and Theory* --** Reliable predictive models
> will be required for all research directions identified in this
> report. The capabilities must span from large-scale continuum models
> for fate and transport to quantum chemical models that can predict
> molecular recognition events. The challenge is to not to just span
> these multiple length scales, but to provide continuity between the
> multiple techniques needed to cover these multiple length and time
> domains.

## Research Environments and Infrastructures

The presentations and discussions at this meeting have made it
abundantly clear that progress toward countering terrorism will require
the formation of science and technology teams that combine multiple
scientific disciplines and span from basic research to systems
engineering and manufacturing. Given this need for broad research and
technology teams, it is important to explore new opportunities to
improve the coupling between academic, national laboratory, and
industrial research and development communities. The workshop
participants agreed that the DOE national laboratories, in general, and
the highly collaborative research facilities such as the Combustion
Research Facility, the Environmental Molecular Sciences Laboratory, or
the newly initiated Nanoscale Science Research Centers, in particular,
could provide a fertile environment for nucleating these new research
teams and associated collaborative science and technology projects.

**[Recommendation:]{.underline}** *We recommend the development of new
collaborative programs that can help to stimulate the formation of, and
provide needed resources for, cross-disciplinary and multi-institutional
collaborations focused on critical needs for countering terrorism.*

The workshop discussions also pointed out the importance of DOE
specialized and user facilities. Existing BES scientific user facilities
at DOE laboratories and universities, coupled with those currently under
development, such as the Nanoscale Science Research Centers, will
provide many important capabilities needed to address critical
scientific issues associated with threats of terrorism. However, we
recognize that no single institution possesses all the required assets
to address these complex problems. It will be important that research
and technology teams are able to take full advantage of the spectrum of
capabilities available at the DOE national laboratories and
university-based programs.

**[Recommendation:]{.underline}** *We recommend continued investment in
DOE specialized and user facilities and explore new mechanisms that
enable research teams to "mix and match" capabilities needed for larger
collaborative projects.*

The topic of radiological and nuclear threats presents a unique
situation in which the Office of Science has the stewardship role for
fundamental research in these areas. Resources allocated to these areas
have, in general, been decreasing over the last three decades, resulting
in a net loss of personnel and aging infrastructure, including a lack of
modern equipment. These problems are not only acute at the national
laboratories, but are also reflected at universities where faculty
positions and studies in radiochemistry and nuclear chemistry have been
rapidly declining.

**[Recommendation:]{.underline}** *We recommend exploring approaches to
stabilize or increase the basic research funding in radiation effects
and nuclear and radiological materials programs particularly as they
apply to terrorist threat reduction and defense programs.*

## Relationships with Other Programs

The task of countering terrorism provides challenges that are extremely
complex and broad. Advice from our plenary speakers and the results of
our own technical and scientific discussions served to reinforce the
point that no one organization or federal agency will be able to provide
all of the tools and capabilities that are needed to meet this
challenge. This report cites examples that show how pooling the
strengths of various organizations within the DOE itself could provide
greater opportunity to address the complex problems associated with
countering terrorism. In addition, it will be important for DOE to
develop strategic alliances with other federal agencies whose missions
and capabilities strongly complement those of the DOE.

The examples cited in this report range from agreements that would
provide the research community with appropriate access to specialized
facilities for handling chemical and biological toxins to alliances that
would facilitate the communication of new scientific developments and
accelerate their application to important counter terrorism
applications.

**[Recommendation:]{.underline}** *We recommend evaluation of
complementary relationships with other organizations and agencies and,
where appropriate, work to develop agreements that facilitate the
formation of multi-organizational teams and the sharing of capabilities
that will improve our nation's ability to counter the threat of
terrorism.*

## Dual-Use Opportunities

Many examples cited in this report show how critical science and
technology challenges associated with countering terrorism could also
impact important needs in energy, national defense, environment, and
human health care. However, the key requirements for the success of any
of these dual-use opportunities are as follows: (1) a clear
understanding of the technology needs and (2) an effective pathway to
move from laboratory / bench-top demonstrations and prototypes to
low-cost, manufacturable technologies that can be widely implemented. In
fact, the key requirements serve to further reinforce the value of
strong technical teams and complementary relationships with other
organizations, especially including industry. The simple fact is that no
new scientific discovery or technological solution will benefit our
nation's counter-terrorism effort or any other important national need
if we are unable to translate that new science into useful and
cost-effective technology.

# Appendix I - CT Roster {#appendix-i---ct-roster .unnumbered}

***Thirteen National Laboratories Represented and 8 Non-BES
Organizations***

[^1]: These areas of research include Materials Synthesis and
    Processing, Biomolecular Materials and Interfaces, Physical &
    Chemical Properties of Materials, Surfaces, Interfaces and Thin
    Films, Nanoscale Materials and Structures, Nano- and Micro-scale
    Diagnostics, Microfabrication, Atomic and Molecular Spectroscopy,
    Catalysis and Chemical Transformations, Separations and Analysis,
    Radiation Effects, Heavy Element Chemistry, and Biochemistry.

[^2]: A. A. Fatah, J. A.; Barrett, R. D. Arcilesi, D.J. Ewing, C. H.
    Lattin, and M. S. Helinski, *Guide for the Selection of Chemical
    Agent and Toxic Industrial Material Detection Equipment for
    Emergency First Responders,* NIJ Guide 100-00, Volume I, June 2000,
    NCJ184449.

[^3]: "Chemical and Biological Terrorism: Research and Development to
    Improve Civilian Medical Response," Committee on R&D Needs for
    Improving Civilian Medical Response to Chemical and Biological
    Terrorism Incidents, Health Science Policy Program, Institute of
    Medicine; and Board on Environmental Studies and Toxicology,
    Commission on Life Sciences, National Research Council, National
    Academy Press, Washington, D.C.; 1999.

[^4]: R. A. Jenkins, M. V. Buchanan, R. Merriweather, R., R. H. Ilgner,
    T. M. Gayle, and A. P. Watson, *J. Hazardous Material* 1994, *37*,
    303.

[^5]: GAO/T-NSIAD-00-50

[^6]: T. Arusi-Parpar, D. Heflinger and R. Lavi, "Photodissociation
    followed by laser-induced fluorescence at atmospheric pressure and
    24 ^o^C: A unique scheme for remote detection of explosives," *Appl.
    Opt.*, 40, 6677- 6681 (2001).

[^7]: Y.-C. Yang, *Acc. Chem. Res*. 32 (1999) 109.

[^8]: J. L. Dey*, Inorg. Chem* 36(1997) 3816 and JACS 124 (2002) 1170