June 2006

Trends and Opportunities in

Photonics Technologies:

Solid-State Lighting and Healthcare

NISTIR 7305

National Institute of Standards and Technology • Technology Administration • U.S. Department of Commerce

Grady S. White

Kris A. Bertness
NISTIR 7305

June 2006

Trends and Opportunities in Photonics 

Technologies: Solid-State Lighting and 

Healthcare 

Grady S. White

Ceramics Division

MSEL

100 Bureau Dr. Stop 8520

Gaithersburg, MD 20899

Kris A. Bertness

Optoelectronics Division

EEEL

Mailcode 815.04

325 Broadway

Boulder, CO 80305

U.S. Department of Commerce 

Carlos M. Gutierrez, Secretary

Technology Administration

Robert Cresanti, Under Secretary of Commerce for Technology

 
TABLE OF CONTENTS 

I. INTRODUCTION 4

II. SOLID-STATE LIGHTING (SSL) 6 

A. Current Status 6

B. White Light Generation 8

1. Blue light source with fluorescing particles 8 

 2. UV LED with fluorescing particles 9 

 3. Three Color LEDs/OLEDs 10

C. Scientific and Technical Barriers 10

 1. 1 – 3 year time frame 14

 2. 5 – 10 year time frame 17

 3. Additional considerations 20

D. NIST Interaction Opportunities in SSL 21

 1. DOE 21

 a) NIST Laboratories 

 b) ATP

 2. NEMA 22

 a) NIST Laboratories 

 b) ATP

 3. Next Generation Lighting Industry Alliance 22 

 a) NIST Laboratories 

 b) ATP

 4. OIDA 23

 a) NIST Laboratories 

 b) ATP

E. NIST Laboratory Research Opportunities 23

 1. Inorganic devices 24

 2. Organic specific 25

III. PHOTONICS IN HEALTHCARE 26

A. Current Status 26

 1. Clinical 27

2. Research and development 27

 a) In vitro 27

 i. Optical microscopy 28

 ii. Spectroscopy 34

 iii. Combinatorial approaches 35

 b) In vivo 35

 i. Imaging 36

 ii. Diagnostics 39

 iii. Treatment 39

B. Long-term issues 40

 1. Implant/biomarker issues 41

 2. Imaging/spectroscopy 41

 

3
C. NIST Interaction Opportunities in Photonics in Healthcare 42 

 1. Food and Drug Administration 42

 a) NIST Laboratories 

 b) ATP

2. National Institutes of Health 43

 a) NIST Laboratories 

 b) ATP

 3. National Science Foundation 44

 a) NIST Laboratories 

 b) ATP

D. NIST Research Opportunities 44

IV. REFERENCES 46

V. APPENDIX I: NIST staff sources for this report 49

VI. APPENDIX II: Non-NIST sources 51

VII. APPENDIX III: ATP-funded projects 56

VIII. APPENDIX IV: Benefits accrued to ATP detail 58

TABLES and FIGURES

Table 1: Sector and CRI estimates of teralumen-hours 6 

lighting demand in 2005 

Table 2: Typical efficacies of LEDs/OLEDs in 1999 7 

Table 3: Strengths and weaknesses of current optical techniques 26 

 (Healthcare) 

Figure 1: Three approaches to generate a solid state white lamp 9 

Figure 2a: Scientific and technical barriers to LEDs 12 

Figure 2b: Scientific and technical barriers to OLEDs 13 

Figure 3: Confocal microscope schematic 29 

Figure 4: Two-photon energy schematic 30 

Figure 5: Higher harmonic generation 31 

Figure 6: Fluorescent resonant energy transfer schematic 32 

Figure 7: Total internal reflections schematic 33 

Figure 8: Flowchart showing sequential, semi-independent relationship 36 

between diagnosis, treatment, and treatment evaluation in current 

medical practice 

 Figure 9: Penetration depth through water and hemoglobin across the visible 37 

wavelength range 

 Figure 10: Schematic of future use of photonics in medical care 40 

4
I. INTRODUCTION 

Photonics, the use of photons in optics, laser technology, electrical engineering, materials 

science, or information storage and processinga

, has migrated from being almost 

exclusively associated with research laboratories into mainstream industrial and 

consumer markets across the economy, including information technology, healthcare, 

security and safety, and lighting. In this document, we consider emerging photonic 

applications in the areas of solid-state lighting (frequently referred to as SSL) and 

medical applications. Our purpose is to provide a snapshot of the current state of 

photonics, as applied to SSL and healthcare, as well as to provide an estimate of future 

directions and anticipated achievements in these fields in the five to ten year time frame. 

At the same time, we will endeavor to highlight major technical barriers, as currently 

perceived, to reaching those goal. We base this document on a variety of sources of 

information. As detailed in Appendices I and II, we have interviewed NIST staff, both in 

the ATP and in the laboratories, representatives of other government agencies, and 

representatives from a variety of private companies. In addition, we have consulted 

reports and roadmaps generated by industrial consortia and government funding agencies. 

Because the issues in SSL and healthcare are quite different, the two topics will be 

considered in separate sections. However, the format for the sections will be the same: 

 

1) a description of the current status, including a synopsis of both the technology 

 and the current applications, 

2) a discussion of where the technology and applications are expected to be 

 moving in the 1 to 10 year time frame, and 

3) the technical/scientific barriers that need to be overcome for anticipated 

 progress to occur. 

It is our intention that this document provides insight both for the ATP to identify 

technical areas for expanded outreach activities and for the NIST laboratories to identify

potentially high-impact areas for future research. To assist with this goal, we have 

included, in Appendix III a list of current and past ATP-funded projects in the areas of 

SSL and photonics in healthcare. 

It should also be recognized from the outset that, because of regulatory considerations,

the business models for healthcare applications are necessarily quite different from those 

for SSL. With SSL, an analysis of scientific barriers, device effectiveness, and cost 

comparisons provides a reasonable predictor of market penetration and economic benefits 

for specific applications. However, because safety concerns override economic benefit, 

healthcare applications, i.e., drugs, treatments, or devices, must undergo an additional 

level of scrutiny. This scrutiny is typically applied through clinical trials, which are both 

 

a The American Heritage® Dictionary of the English Language, Fourth Edition

Copyright © 2000 by Houghton Mifflin Company. Published by Houghton Mifflin 

Company.

5
expensive and time consuming. Because of the expense of the clinical trials, companies 

sometimes view certain products, which might prove highly competitive in niche 

markets, as not worth pursuing. In addition, unsuccessful or partially successful results 

of clinical trials can either terminate or greatly alter potential market applications in all 

healthcare products. The applications of photonics in healthcare discussed in this 

document are almost all in the pre-clinical testing stage. Therefore, while we discuss 

market and economic predictions due to advances in SSL, with regard to healthcare, we 

restrict our discussions to potential applications and do not attempt to predict market 

impacts. 

6
II. SOLID-STATE LIGHTING (SSL)

Solid-state lighting is the name given to lighting generated through exciton 

recombination rather than through black body radiation (standard incandescent or 

halogen) or gas discharge (fluorescent or High Intensity Discharge). The basis of solidstate light emitting devices consists of an electron-rich (or easily injected) region and a 

hole-rich (or easily injected) region separated by a carrier depleted zone. When a voltage 

is applied electrons and holes are injected into the depleted region where they recombine, 

emitting light. This rather broad brush description is applicable to both light emitting 

diode (LED) based lamps, which are composed of traditional semiconductor materials, 

and organic light emitting diodes (OLED’s), which are made of conduction and emission 

organic layers. 

A. Current Status

The primary driving force for the development of solid-state lighting is the reduction of 

energy use, with concomitant reductions in chemical pollution, light pollution, and cost to 

the consumer. According to a 2003 report1

 by the Next Generation Lighting Industry 

Alliance (NGLIA), in 2001, 22% of the electricity generated in the United States was 

used for lighting. This is the equivalent output of 100 power plants, each generating 

1000 MW, for a total cost of 55 billion dollars. The lighting requirements for 2005 in the 

United States are shown in Table 12

, broken down into residential, commercial, 

industrial, and outdoor categories and into low, medium, high, and very high color 

rendering index (CRI)b

 bins. 

Table 1: Sector and CRI estimates of teralumen-hours lighting demand in 2005 (after 

Reference 2)

(Tlm-h/y) Residential Commercial Industrial Outdoor CRI-Bin 

Total 

Low CRI 33 1,021 711 4,145 5,910 

Medium

CRI 

1,336 12,451 3755 572 18,113

High CRI 62 7,932 4,258 64 12,316 

Very High 

CRI 

2,632 1,956 41 88 4,717

Totals 4,062 23,361 8,765 4,868 41,056

 

Table 1 shows that commercial lighting is expected to account for 74% of the generated 

light. For very high CRI, residential applications account for fully 55% of the usage. 

According to the NGLIA report1

, when LEDs and OLEDs reach 150 lum/W for white 

light generation, the United States will be able to reduce its annual consumption of 

electricity by 6% - 7%, equivalent to about $17 billion. This reduction is projected to 

 

b

 The CRI is a parameter that quantifies how closely the appearance of a set of eight pastel colors 

illuminated by a test lamp compares to the appearance when illuminated by an accepted “standard” lamp of 

the same light temperature (i.e., warmth). The maximum value of the CRI is 100, which corresponds to an

appearance identical to that obtained from the reference lamp. 

7
result in reductions of pollutants on the order of 150 x 106

 tons of CO2, 0.3 x 106 tons of 

NOx, and 0.67 x 106

 tons of SO2. However, the current status of SSL sources falls well 

short of the 150 lum/W goal (in 2004, white LEDs lamps achieved ≅ 30 lum/W). Table 2 

shows efficacy values3 for three LEDs and one OLED that span the visible spectral range 

in 1999. 

For comparison, an unfiltered incandescent lamp2

 has an efficacy of 10 – 25 lum/W and 

fluorescent lamps

2

 reach 50 - 95 lum/W, depending upon the specific lamp geometry and 

application. By 2005, commercial LEDs improved to 100 lum/W at 50% wall plug 

efficiency.4

 In addition, commercial solid-state white lamps that provide 60 lum are now 

available, although they only provide about 15 lum/W. At this time, the DOE “World 

Record” for white lamps

5

 is 74 lum/W for a laboratory LED and 20 lum/W for a 

laboratory OLED. Clearly, substantial progress needs to occur before the 150 lum/W

goal is achieved. 

Table 2: Typical efficacies of LEDs/OLEDs in 1999 (after reference 3) 

Material Color Efficacy 

InGaN Blue >10 lum/W

InGaN Green >25 lum/W

OLED Green >25 lum/W

AlInGaP/GaP Red/orange >100 lum/W

Along with the primary benefit of energy conservation, a number of secondary benefits 

also accrue with SSL. Possibly the most important secondary benefit is reliability. 

Today, blue LEDs provide over 5,000 h of light and red LEDs can last well over 100,000 

h. When failure occurs, it is seldom catastrophic, as for incandescent and fluorescent 

lamps; rather, LEDs typically fail via a gradual diminution of light output over time. The 

long lifetimes and the non-catastrophic failure processes explain why LEDs have already 

made substantial inroads replacing incandescent traffic signal lamps and have almost 

completely replaced all other lamps for use in emergency exit signs throughout the 

United States.6

 In another aspect of reliability, the absence of breakable filaments 

contributes to make the idea of SSL attractive as light sources in environments inherently 

subject to vibration; e.g., instrument control lamps in all forms of transportation, 

overhead reading lamps in aircraft, brake lamps in automobiles and trucks, and vanity 

and door panel lamps in automobiles. 

In addition to these prosaic, albeit important, benefits, SSL opens the possibility that

architects, designers, and casual users of lighting will easily be able to achieve or to 

modify lighting-induced ambience without having to resort to energy robbing filters or 

having to maintain a collection of expensive specialty lamps. These possibilities include, 

but are not limited to, varying lamp color by mixing relative intensities of different 

colored LEDs or OLEDs, of dimming lamps without altering their color output, and, for 

OLEDs, of designing entire walls, table tops, or any other continuous surface to act as a 

controllable, distributed light source.7

 Finally, there are many niche markets that, while 

8
forming only a small part of the overall lighting energy budget, would still provide 

substantial energy savings if incandescent lamps were replaced by SSL; the most 

important of these niche applications are holiday lighting and commercial signage.6

However, for SSL to displace most of these applications and, certainly, for it to 

disruptively take over any significant portion of the white light market, three advances 

must occur: 1) the price must come down (for white LEDs, a reduction of x100 is 

needed), 2) the efficiency must increase, and 3) the reliability must increase (this is 

especially important for OLEDs although it is also true for blue, green, and yellow 

LEDs). Because white-light lamps and area lighting form the largest component of the 

lighting budget and because efficient, reliable, and cheap generation of such white light 

from LEDs and OLEDs, which are inherently narrow in spectral output, forms the 

greatest barrier to the displacement of incandescent and fluorescent lamps by SSL, the 

remaining discussion of SSL will focus primarily on white lamps. 

B. White Light Generation

There currently are three mechanisms by which solid-state lamps can produce white 

light:3

 

1) use of a blue source surrounded by a matrix containing one or two kinds of 

 fluorescing particles, i.e., particles that will fluoresce in one or two 

 wavelengths, 

2) use of an UV LED surrounded by a matrix containing several different types of 

 fluorescing particles, and 

3) use of multiple active sources, either LEDs or OLEDs, to generate white light

 (Figure 1). This third approach avoids the need for fluorescent particles. 

While it is commonly felt that the third approach will be the most efficient and is the 

most versatile, the first two approaches are more likely to enter the marketplace first.3

 

Advantages and disadvantages with each approach are enumerated below. 

1. Blue light source with phosphor particles

This approach uses a blue source that is surrounded by a matrix containing a single, 

yellow-fluorescing particle or a matrix containing two different fluorescing particles, e.g., 

a red and a green. The phosphor material can be a traditional fluorescent, similar in 

behavior although quite different in material requirements to coatings in fluorescent 

lamps, or the material could be made up of quantum dots (QDs). In either case, the lamp

concept is the same. Because the phosphor particles only partially occlude the blue light 

source and because the capture and conversion efficiency of blue light by the fluorescing 

particles is less than 100%, the light out of the lamp is a combination of the fluorescing 

wavelength(s) and the original bluesource wavelength. By choosing phosphor particle 

wavelengths appropriately, the combination of fluorescence and blue source light results 

in a white output. Two of the main difficulties with this approach are the “halo” effect 

9
and weak blue light absorption. The halo effect arises because the light from the blue 

diode is directional while the light from the phosphors is uniformly distributed. 

Consequently, while the center of the light spot appears white, the edges are dominated 

by the phosphor emission. Weak blue absorption requires thick phosphor layers. 

Currently, research is underway to make the diodes less directional in their output and to 

develop phosphor materials that are more efficient in both photon capture and photon 

emission. 

Figure 1: Schematics of the three approaches to making a white lamp. All three approaches involve 

placing LEDs or OLEDs (colored rectangles) on a conductor and substrate (shown schematically as the 

black rectangle). A transparent electrode is placed over the diodes and the entire system is enclosed in a

hermetic seal that often acts as a lens. Differences in the approaches: a) A blue emitting LED excites a 

phosphor containing layer that emits complementary color(s), e.g., yellow. The combination of blue and

phosphor generated colors gives a white light. b) An UV emitting diode excites a phosphor containing 3 

colors whose combination gives a white light. c) Three distinct diodes emit red, green, and blue to give a 

white light. 

2. UV LED with fluorescing particles 

This approach is similar to the blue light source approach except that the LED output 

does not contribute to the visible light output. Therefore, all of the wavelengths required

for white light generation must be supplied by the phosphors (i.e., phosphors for blue 

10
output must be included into the layer). The UV excitation results in high CRI values but 

it also means that the phosphor particle, in addition to being thermally stable, must be 

stable under UV radiation. Additionally, because the LED is not contributing to the 

visible output, the phosphor particles must be highly efficient in converting the UV light. 

Finally, because UV radiation typically degrades polymers, this approach is more likely 

to be used for LEDs than OLEDs. 

3. Three Color LEDs/OLEDs 

Use of three independent colored LEDs to generate a white light has two important 

advantages. First, by avoiding the need for phosphor particles, the conversion efficiency 

of the phosphors no longer limits the efficiency of the lamps. Second, because the light is 

being generated directly from the LEDs/OLEDs, the output color can be controlled by 

individual control of the separate LEDs or OLEDs, i.e., intelligent pixel management. 

However, this control can be difficult, as pointed out in a report from the Optoelectronic 

Industry Development Association3

: while “[i]n the long term, this option may be the 

preferred method for producing high quality white light for general illumination,” these 

benefits come at a cost. “... [B]ecause the ... different color components have different 

voltage requirements, different degradation characteristics and different temperature 

dependencies, a sophisticated control system might be required.”3

 In addition, the 

lifetime of the lamp will be determined by the minimum lifetime of the various 

LEDs/OLEDs that contribute to the white light. Currently the lifetime of red LEDs is 5 

times that of blue LEDs. To achieve the desired lamp lifetimes, degradation mechanisms

for the blue, green, and yellow sources must be identified and solutions to the degradation 

must be developed. Finally, there currently are no efficient green LED candidates. 

Therefore, for solid-state white lamps, without phosphor particles, there is an urgent need 

for the development of green LEDs to achieve the correct color control. 

C. Scientific and Technical Barriers

The process of generating white light from solid-state sources requires several steps, each 

of which involves its own loss mechanisms and concomitant cost in efficiency. Because 

the overall device efficiency is the product of these individual efficiencies, each step in 

the process must be optimized to maximize the overall efficiency of the final device. A 

simplistic description of the key processes involved in developing a white lamp will help 

clarify the research and development prioritization schemes that are discussed below. In 

SSL, photons are generated via recombination of electrons and holes. Mechanisms that 

reduce carrier concentration, carrier mobility, or non-radiative exciton recombination 

limit the net output of the device. Therefore, such things as electric fields that inhibit 

charge injection, Fermi surfaces that reduce mobility, and point/distributed defects that 

act as alternative trapping sites, need to be identified and reduced or eliminated in order 

to increase light generation. Once generated, photons must escape the material without 

being reabsorbed or scattered into non-productive pathways. Consequently, the active 

region needs to be thin, the index of refraction for the surrounding material needs to be 

large and the geometry of the active region needs to be designed to minimize internal 

reflection. If the white lamp depends on down-conversion of blue or UV light, the 

11
efficiencies of the phosphor particles in capturing the excitation photons and in 

converting the energy of the captured photons into light act as additional limiting factors 

on the overall efficiency of the lamp. Additionally, for down-conversion lamps, the 

phosphor particles and their surrounding matrix must withstand high intensities of blue or 

UV light with minimal property degradation in order for the lamp to achieve the desired 

lifetime of multiple tens of thousands of hours. Finally, thermal management of the lamp

is essential at all scales. While SSL generates light by direct electron/hole recombination 

rather than by joule heating, as an incandescent lamp does, the fact remains that, if a lamp 

has a 50% wall plug efficiency, as the best commercial LEDs currently do, then half of 

the energy used by the lamp will be converted to heat. If SSL is improved to achieve the 

goal of 80% wall plug efficiency, there will still be 20% of the energy being used to 

generate heat within the lamp. While much less energy is being used to generate heat in 

SSL than in incandescent lamps, the heat is being generated in very small volumes and 

can result in locally large thermal excursions that lower the efficiency, alter the output 

wavelengths, and degrade the lifetimes of the lamps. Therefore, thermal management is 

a critical aspect of SSL design from the semiconductor size scale all the way through the 

lamp and housing scale. These various issues form the basic conceptual barriers that 

must be addressed for SSL to function. However, for SSL to succeed as an industry, the 

solutions to these barriers must be economical and practical as well as scientifically 

possible. 

At the spring Department of Energy (DOE) SSL Workshop and Program Review8

 held in 

San Diego, CA, February 3-4, 2005, industry, national lab, and university representatives 

discussed the scientific and technical barriers that must be overcome for SSL to displace 

incandescent and fluorescent lighting. The identified barriers were prioritized in terms of 

urgency and, based upon that prioritization, were placed into 2 – 3 year or 5 – 10 year 

time-frame bins. Because the barriers are essentially the same as those previously 

identified by the Optoelectronic Industry Development Association (OIDA),3

 the 

NGLIA,1

 National Electrical Manufacturers Association (NEMA),9 and a presentation 

made by a SSL company, LUMILEDS, at a DOE conference on SSL,10 the discussion of 

technical barriers and priorities below will focus predominately on the consensus-based 

conclusions reached at the February 2005 DOE Program Review. 

Figure 1 lays out the primary barriers that must be overcome for SSL to break into the 

lighting industry at a substantive level. The figure is divided into issues associated with 

inorganic SSL, or LEDs (Fig. 1a), and those associated with organic SSL, or OLEDs 

(Fig. 1b). Issues are divided into needed progress for both LEDs and OLEDs: 

• further research and understanding are necessary (Core Technology) 

• basic understanding is (or will be) in place and the remaining barriers are 

engineering and economic (Product Development). 

Items that are italicized were, by consensus of the participants, determined to be the most 

urgent items; i.e., issues that need to be addressed in the 1 – 3 year time frame. The 

remaining items need to be addressed in the 5 – 10 year time frame or, in a few cases, are 

expected to be issues that would be addressed by individual companies on a proprietary 

12
13
14
level rather than on a consortium level. The following discussion addresses topics in 

both the 1 – 3 year time frame and the 5 – 10 year time frame. The ordering presented in 

the 1 – 3 year time frame discussion has no significance; the five items at the workshop

that received the largest number of votes in each category were designated as the most 

urgent. The number of attendees at the workshop was not large enough to allow a 

meaningful prioritization of the five “most urgent” items in each category. 

1. 1 – 3 year 

a) Inorganic Core Research 

In this area, the five most urgent research areas are: 1) large area substrates, buffer layers, 

and wafer research; 2) high-efficiency semiconductor materials; 3) device architecture 

approaches, structures, and systems; 4) strategies for improved light extraction and 

manipulation; and 5) phosphors and conversion materials. Some of the key aspects of 

each of these areas are: 

1) Large area substrates, buffer layers, and wafer research 

a. Defects in substrates that propagate into the film active areas act as nonradiative recombination sites that degrade the efficiency of the lightemitting devices built on the substrates. Therefore, defect reduction in 

substrates is a high priority. However, defect reduction becomes 

increasingly difficult as substrates with larger areas are grown. 

b. Ideal buffer layers between the substrates and the actives layers will not 

only isolate the active layers from defect propagation from the substrate 

but will also reduce dislocation formation in the active layers that results 

from thermal expansion mismatch between the substrate and subsequent 

film layers. The buffer layers need to accomplish this while allowing a 

high level of crystalline perfection in the active layer. 

c. Research into fabrication of high quality (i.e., low defect density) wafers 

that come close to lattice matching the active layers could result in much 

lower dislocation densities in the active layers and avoid the need for the 

buffer layers. The nitrides are prime contenders in this area. In addition, 

ZnO is being investigated as a material that provides an alternate path. 

2) High-efficiency semiconductor materials 

a. As mentioned previously, one of the highest priorities for multicolor LED 

white lamp fabrication is the development of an efficient, long-lived green 

LED. 

b. In addition to development of an adequate green LED, cost reduction and 

reliability improvement of all of the nitride-based and ZnO-based LEDs 

remain high priority research areas. Increasing the active area, i.e., defect 

free region, of nitride films would provide an economy of scale as well as 

lead to more efficient LEDs. 

3) Device architecture approaches, structures, and systems 

Directional light emission, either through light generation via directed 

sources, e.g., lasers, or through post-generation guidance, e.g., photonic 

crystals, would help alleviate light extraction issues associated with internal 

15
reflection. Directional sources would also be valuable in the development of 

SSL spot sources or accent lamps that would provide light where needed 

while reducing wasteful and undesirable light pollution. In addition, 

improved procedures such as surface preparation, e.g., roughening and 

faceting, or index matching to reduce internal scattering and improve 

extraction efficiency, fit within this task definition. 

4) Strategies for improved light extraction and manipulation 

This task has the same goal as task 3, above. However, the emphasis here is 

on modeling or highly innovative ideas that can be used to increase light 

extraction and directional control. 

5) Phosphors and conversion materials 

a. Optimization of deposition methods, particle packing and distribution, 

particle layering, particle conversion efficiency, and matrix optical 

properties are critical to enhancing the efficiency of the down-conversion 

of the incident light. This task also includes issues such as design 

requirements to enhance forward scattering, rather than backscattering of 

the incident light and reduction of secondary absorption in the 

phosphorescing particles. 

b. In addition to control of initial optical properties and conversion 

efficiencies of the phosphorescent particles, SSL requires long-term

stability. Therefore, degradation mechanisms, via exposure to high 

intensity incident light, high local thermal excursions, chemical interface 

interactions, etc., must be identified and quantified, and strategies for 

minimizing degradation must be developed. 

 

b) Inorganic Product Development 

The corresponding five most urgent items for inorganic LED “Product Development” 

are: 1) integration of manufactured materials, 2) integration of LED packages and 

packaging materials, 3) optical coupling and modeling, 4) integration of electronics 

design, and 5) integration of thermal design. 

1) Integration of manufactured materials 

The integration of the phosphor particles with the encapsulate material and 

mounting materials must include optical, thermal and chemical compatibility 

of each of the individual materials as well as stability among the materials. 

2) Integration of LED packages and packaging materials 

a. Integrated packages must include compatibility with both electrodes, and 

commercial design requirements as well as a thermal management system 

( i.e., thermal pathways to dissipate heat without interfering with optical

requirements). 

b. Compatible electrodes must be chosen to fit package design requirements, 

e.g., transparent or opaque, low resistance, high adhesion. 

3) Optical coupling and modeling 

Although each of the individual material optical properties was addressed 

under “Core Technology”, the integration of the elements can lead to 

16
unforeseen complications. In particular, optical paths and optical interfaces 

must be carefully modeled and designed to achieve high efficiency lamps. 

4) Integration of electronics design 

As alluded to previously, the electronics for SSL must be designed to provide 

the required voltages and currents without occluding the optical pathways and 

while maintaining the desired form factor. The electronics must also be 

designed to minimize joule heating in the lamps. In the case of multi-LED 

lamps, the current and voltage requirements, and associated controllers, for 

each LED must be designed and then integrated into a single package. 

5) Integration of thermal design 

Thermal issues have been mentioned several times previously and thermal 

management must be incorporated at each step in the lamp design. The 

integration of multiple materials and, potentially, multiple current and voltage 

sources into very small volumes make thermal management of the entire 

system complicated. Current high intensity white lamps incorporate large 

heat sinks that greatly increase the lamp size and mass. It is commonly 

assumed that future lamps will need to be designed to minimize such heat

sinks, both for practical as well as aesthetic reasons. 

It is important to bear in mind that, in the DOE SSL framework, the tasks listed under 

“Product Development” are expected to require minimal additional research. At this 

stage, the expectation is that the tasks should be headed toward commercialization. 

However, with regard to the NIST mission, the Product Development tasks remain 

important for two reasons. First, as commercialization is begun, issues associated with

standards become more evident. Second, the steps between basic understanding, i.e., 

“Core Technology,” and commercialization lie precisely in the mandated mission of the 

Advanced Technology Program. Therefore, knowledge of these issues could allow DOE 

and NIST/ATP to leverage off of each other’s resources, to the benefit of all. 

c) OLED Core Research 

Exactly the same process was used to identify the five most urgent issues on “Core 

Research” for OLEDS: 

1) High efficiency, low voltage materials; 

2) Approaches, structures, and systems for improved-performance; 

3) Transparent electrodes;

4) Low-cost encapsulation and packaging technology; and 

5) Investigation of low-cost fabrication and patterning techniques. 

d) OLED Product Development 

1) Substrates for electro-active organic materials. 

2) High efficiency, low voltage, stable materials. 

3) Implementing strategies for improved light extraction and manipulation. 

4) Develop architectures that improve device robustness, increase lifetime and 

increase efficiency. 

5) OLED packaging for lighting applications. 

17
It is immediately clear that many of the issues associated with LEDs and OLEDs are the 

same, albeit, because of the differences between material properties of semiconductors 

and polymers, typically different solutions to technical barriers will be required. 

Nevertheless, efficiency, improved device structure, improved light extraction, low cost 

packaging technology, increased lifetimes, and thermal management are critical areas that 

need to be addressed in both materials systems. Indeed, one of the suggestions that came

out of the workshop8

 is that there needs to be “more cross-fertilization between LED and 

OLED” activities. However, because of the inherent differences in long-term stability 

between semiconductors and polymers, there is substantially greater emphasis in the 

OLEDs on low voltage materials, improved performance, and improved lifetimes. 

2. 5 – 10 year time frame

Longer-term research and development requirements exist. Some of the items are 

considered long term because they reflect ongoing improvements and extensions of the 

current state of understanding in the basic sciences that underpin SSL. Others tasks are 

considered long term because their implementation is predicated on solutions being found 

for the more urgent, 1 – 3 year tasks discussed above. 

a) Inorganic Core Technology 

High priority inorganic “Core Technology” research issues in the 5 – 10 year time frame 

are: 1) development of reliability predictions and defect physics for improved LED 

lifetime; 2) development of improved encapsulate and packaging materials; 3) 

development of improved electrodes and interconnects; 4) development of measurement 

metrics and human factors for SSL; 5) improved physical, chemical, and optical 

modeling for epitaxial processes; and 6) design and development of in situ diagnostic 

tools for epitaxial processes. 

1) Development of reliability predictions and defect physics for improved LED 

lifetime. 

a. An improved theoretical understanding and associated experimental 

tools are desired for predicting material or device properties as well as 

device failure interpretation. Current models are more empirical 

and/or qualitative than desired for device design or lifetime prediction, 

particularly as materials used in SSL evolve. 

b. Droop, i.e., efficiency degradation at high temperature and current 

density, is a well recognized but poorly understood phenomenon. 

Accurate theoretical analysis with experimental confirmation is needed 

for droop to be overcome in current device designs and avoided in 

future devices. 

2) Development of improved encapsulate and packaging materials. 

a. Similar to the phosphor particles and the active light generation 

medium that are highlighted in tasks for the 1 – 3 year time frame, 

packaging materials have to withstand elevated temperature, high 

intensity of visible and, perhaps, UV radiation, and environmental 

attack while allowing efficient optical extraction. In addition, the 

18
packaging material has to maintain its properties for the lifetime of the 

lamp. 

b. As discussed previously, thermal management is a ubiquitous and 

potentially limiting issue that must be addressed at every level of lamp

design. 

3) Development of improved electrodes and interconnects. 

Low resistance electrodes and interconnects are important to reduce 

thermal loading and improve lamp efficiency. Additionally, issues such as

adhesion reliability are poorly understood and potentially limit device 

lifetime. 

4) Development of measurement metrics and human factors for SSL. 

a. The interface with human usage and perception is critical for the 

widespread adoption of SSL. Human experience, expectations, and 

preferences for lighting need to be incorporated into lamp design; 

regardless of lamp efficiency and output power, if the lamp output is 

not perceived to be attractive, convenient, or desirable, SSL will not 

replace current lamps in the general lighting market. 

b. Industry definitions of “white” light, and “quality” of light need to be 

developed and adopted. The variation of both white light and quality 

of light with specific applications need to be designed into lamps. 

c. Standards for photometric measurements need to developed and 

adopted by the industry. 

5) Improved physical, chemical, and optical modeling for epitaxial processes. 

Improved theoretical understanding of epitaxial processes needs to be 

developed, both to provide better control of current material systems and 

to provide guidance for material systems of the future. 

6) Design and development of in-situ diagnostic tools for epitaxial processes. 

Tools need to be developed, in parallel with item 5) above, to provide real 

time, quantitative evaluation of film systems. 

b) Inorganic Product Development 

The 5 – 10 year time frame tasks for the inorganic SSL “Product Development” are 

closely tied to success of the 1 – 3 year tasks of the inorganic “Core Research”. In 

particular, four tasks in Materials Development are clearly dependent upon success in 

development of large, low defect density substrates, improved buffer layers, new highefficiency LEDs that span the visible spectrum, and improved high-efficiency phosphors. 

These tasks are: 1) substrate, buffer layer, and wafer engineering and development; 2) 

high-efficiency semiconductor materials; 3) implementing strategies for improved light 

extraction and manipulation; and 4) device architectures with high power conversion 

efficiencies. Two other long-range goals, modeling of coupling issues for device 

integration and luminaire design and field tests, build upon the short-range tasks 1 and 2 

(i.e., packaging issues) for inorganic “Product Development”. The final two “Product 

Development” long-range activities, (a) evaluation of human factors and evaluation of 

lifetime and (b) performance characteristics, are tightly coupled to similar long term tasks 

laid out under “Core Research”. 

19
c) OLED Core Research 

In the 5 – 10 year time frame, the following tasks exist for OLED “Core Research”: 

1) Research into electro-active organic materials for substrates. 

a. Addresses the difficulties associated with achieving efficient charge

injection into the polymer semiconductors from the perspective of 

material development 

2) Improved contact materials and surface modifications for improved charge

injection. 

a. Addresses the difficulties associated with achieving efficient charge

injection into the polymer semiconductors from the perspective of 

interface effects

b. Replaces the insulating substrate and the conducting film that lies 

between the substrate and the semiconducting polymer with an electroactive polymer substrate that has a work function comparable to the 

HOMO level of the semiconductor.

c. One consequence of low charge injection and mobility is the need for 

higher driving voltages (e.g., 10 – 20 volts instead of the desired 4 

volts).

3) Improved understanding of the fundamental physics associated with OLEDs. 

a. The details of charge injection, mobility, and recombination need to be 

better understood for OLEDs. 

4) Strategies for improved light extraction. 

a. This item is similar to the light extraction issues with LEDs discussed 

previously. Non-radiative recombination processes, scattering, and 

re-absorption need to be reduced to improve the efficacy of OLEDs.

5) Down-conversion materials. 

a. Again, the issues in down conversion are the same as the down 

conversion requirements in LEDs: quantum efficiency, long-term

reliability.

6) Integration of electrodes and interconnects. 

7) Measurement metrics and human factors.

a. The issues associated with measurement metrics and human factors 

(e.g., color quality, color acceptability) are identical to those 

mentioned above for LEDs. The longer time frame for this item in 

OLEDs reflects the feeling that efficacy, reliability, voltage, etc. are a 

more urgent priority for OLEDs and that human factors will follow 

after more immediate problems are solved.

8) Improved physical, chemical, and optical modeling. 

a. It is generally felt that modeling tools are not well established for 

OLEDs. This reflects the general feeling that understanding of the 

basic physics in OLEDs is not yet adequate. 

d) OLED Product Development.

In the same time frame, the OLEDs “Product Development” tasks are: 

1) Improved contact materials for improved charge injection; 

2) Demonstration of various device architectures; 

20
3) Simulation tools for modeling OLED devices; 

4) Voltage conversion, current density, power distribution and driver electronics; 

5) Luminaire design and field tests; 

6) Module and process optimization and manufacturing; 

7) Manufacturing scale-up of OLED material; and 

8) Tools for manufacturing lighting modules. 

Issues associated with manufacturability are built closely upon the perceived Core 

Research needs discussed previously. In addition, a number of these tasks mirror similar 

tasks associated with the LED lamp fabrication. These include strategies for improved 

light extraction, improved down-conversion materials, integration of electrodes and 

interconnects, measurement metrics and human factors, improved physical, chemical, and 

optical modeling, demonstration of various device architectures, driver electronics, 

luminaire design and field tests, and tools for manufacturing lighting modules. However, 

other tasks are more specifically related to the polymer aspects of OLEDs. In particular, 

the issues associated with charge injection, electrically active substrates, and 

manufacturing scale-up in OLEDs are quite different from the same issues associated 

with LED lamps. Finally, it should be noted that, while modeling and theory 

development are highlighted as needs for both LEDs and OLEDs, improved 

understanding of the fundamental physics is most pressing for OLED development. 

3. Additional considerations 

In addition to obtaining information from DOE, OIDA (Optoelectronic Industry 

Development Association), and industry sponsored workshop summaries and reports, 

information was also obtained from numerous individuals within various private 

companies involved in SSL development. Conversations were explicitly restricted to 

nonproprietary topics, focusing on generic, industry wide issues that NIST might address, 

i.e., standard reference materials, standard measurement procedures, basic research 

advances. While most of the topics that arose have been covered above, there was a 

repeated emphasis on the thin film aspects of SSL that was not explicitly addressed in 

any of the workshops or reports that we have seen. In particular, concerns exist over 

appropriate measurement techniques and data interpretation for very thin film systems, 

e.g., whether material properties remain the same as films are reduced to tens of nm in 

thickness, and what might be the impacts of reducing size to the point that systems are 

dominated by surface and interface properties rather than by bulk volume properties. In 

particular, questions exist regarding the proper procedures for measuring and interpreting 

thermal conductivity in systems composed of layers of very thin films. How does 

thermal conductivity of a film behave as film thickness decreases? These are particularly 

important problems as device size continues to shrink; designs for thermal management 

in these complicated thin film systems are made using models that assume bulk material 

thermal properties. Similar concerns accrue to other material properties as film

thicknesses continue to shrink; e.g., how do optical properties like index of refraction 

behave? Will delamination become a problem as thicknesses continue to decrease? 

What impact do the large surface/interface areas have on long term reliability? These 

21
questions become increasingly difficult to answer as size scales in SSL devices move into 

the nanometer range. 

D. NIST Interaction Opportunities in SSL

Several organizations exist in the United States that either are currently active in SSL or

have been heavily involved in the recent past. These organizations include government 

agencies, industry consortia, individual companies, and universities. A list of key 

organizations whose output and conclusions have been used in this report is presented 

below. We also provide a short discussion of potential interaction benefits to both the 

NIST laboratories and the NIST ATP for each organization. 

1. DOE

The Department of Energy (DOE) has become the national driver for SSL. This reflects 

three facts: 1) energy conservation is part of thr DOE mission, 2) as the head of a 

collection of national laboratories, the DOE has substantial research resources that it can 

direct towards SSL and 3) as the primary source of non-Department of Defense research 

funding in the United States, the DOE has financial resources to support industry efforts 

in both basic SSL research as well as in commercialization efforts. Two parts of the DOE 

are involved in the SSL program: the Office of Energy Efficiency and Renewable Energy 

(EERE)/Building Technologies and the National Energy Technology Lab (NETL). The 

overall program is directed by Dr. James Brodrick of the Office of Building 

Technologies. 

a) NIST Laboratories 

There are three benefits for the NIST laboratories in working with the DOE SSL 

program. First is the possibility for setting up collaborations with industry or DOE 

laboratory partners who are either currently receiving funding or are attempting to put 

together a research plan in order to receive future funding. Second is that the SSL 

program provides a prioritized list of research areas with clearly associated industry 

impacts that can help to guide NIST laboratories research choices. Third is the potential 

to leverage funding for LED or OLED material or device issues for both agencies. 

Priorities are re-evaluated yearly at the DOE program reviews, in light of yearly progress 

and potentially evolving priorities. 

b) ATP 

As discussed previously, the DOE SSL program is divided into two components: “Core 

Research” and “Technology Development”. Funding for Core Technology is intended to 

provide resources for overcoming scientific barriers to SSL. Funding for Technology 

Development is not intended for research; rather, it is intended for product development 

and commercialization. One feature of the DOE SSL program is that an industrial 

organization, the Next Generation Lighting Industry Alliance (NGLIA), provides 

technical guidance and has access to patented non-commercialized intellectual property 

(IP) that is developed under SSL Core Technology funding (see discussion below). An 

opportunity for the ATP is to provide funding to small companies that have patented IP 

22
but have remaining high risk scientific/technological barriers to overcome prior to 

commercialization. These conditions precisely meet the ATP mandate. 

2. National Electrical Manufacturers Association (NEMA) 

NEMA “is the leading trade association in the U.S. representing the interests of

electroindustry manufacturers of products used in the generation, transmission and 

distribution, control, and end-use of electricity.”9

 As part of its activities, NEMA 

develops manufacturing roadmaps, develops standards, and lobbies for the interests of 

manufacturers in the electric and electronic industries. Recently, NEMA has expanded 

its activities to include SSL. As one of the activities associated with SSL, NEMA 

manages NGLIA, although NGLIA is not a part of NEMA. 

a) NIST Laboratories 

Many NIST staff members participate in NEMA road-mapping efforts and in standards 

activities involving NEMA. NIST management also has a history of involvement with 

NEMA, e.g., attending meetings and giving presentations. These activities provide 

guidance as to industrial directions, allow NIST staff to develop relationships with 

industrial counterparts, and enhance opportunities for the NIST/industry collaborations. 

b) ATP 

Outreach activities to NEMA, via road-mapping activities, standards work, or meeting 

attendance, would provide ATP staff with the same opportunities as the laboratory staff 

to develop personal relationships with industry members as well as, both formally and 

informally, educate industry counterparts regarding the existence and purpose of the 

ATP. In addition, participation of ATP staff in road-mapping and/or standards 

discussions enhances ATP stature as being technically aware, informed and active. 

3. Next Generation Lighting Industry Alliance (NGLIA)

The NGLIA is an industry consortium focused on SSL under the DOE program. One of 

the benefits of being a member of the NGLIA is that any patented IP developed under the 

DOE SSL “Core Research” Program that is not in the process of being commercialized 

one year after the patent award is available to any consortium member under a nonexclusive license for “reasonable terms”.11 The consortium is managed by, though not a 

part of the National Engineering Manufacturing Association (NEMA). As of February, 

2005, the consortium members are: Corning, Cree, Dow/Corning, General Electric, 

GELcore, Kodak, Lumileds, OSRAM, Philips, and 3M. 

 

a) NIST Laboratories 

The primary potential benefit to the NIST laboratories for interaction with NGLIA is that 

NGLIA research directions and goals are shared by the major companies involved in the 

SSL industry. This provides guidance to the laboratories regarding the potential 

economic impact associated with SSL research directions. In addition, because the 

NGLIA provides technical guidance to the DOE regarding SSL road mapping, NGLIA 

endorsement of the importance of a proposed NIST laboratory activity enhances the 

importance that the DOE will place on the proposal. 

23
b) ATP 

If the ATP is conducting outreach activities to NEMA and sets up a relationship with 

DOE that will allow presentations at the DOE SSL program reviews, an explicit outreach 

activity to NGLIA sponsored meetings may be repetitive. This is particularly true since 

most of the members of NGLIA are clearly aware of both the existence and purpose of 

ATP, having submitted proposals in the past. 

4. Optoelectronic Industry Development Association (OIDA) 

OIDA is an industry consortium made up of predominately U.S. companies involved in 

photonics. As recently as 2000, manufacturers making up 80% of the dollar value of

photonics manufacturing and sales in the United States were members of the OIDA. 

Until the recent economic downturn, fiber optic communications, networking, and optical 

computing were the main thrusts of OIDA. Around 2001, the OIDA began promoting the 

importance of SSL and educating Congress regarding the relevant issues. Since that 

time, the DOE has become the champion for SSL and the OIDA has turned its focus 

toward optical sensors. Nevertheless, the OIDA has organized excellent workshops and 

published reviews of the issues associated with SSL that provide important and relevant 

information. 

a) NIST Laboratories 

The NIST laboratories have had a close working relationship with the OIDA for many 

years. This is particularly true for the Optoelectronics Division in the EEEL, which has 

based much of its choice of technical direction upon OIDA-generated roadmaps. 

However, because the OIDA represents such a large portion of the optoelectronics 

industry, CSTL, MSEL, and PL also have a track record of interacting with the 

organization, both in conducting research suggested by OIDA roadmaps and in 

participation at OIDA meetings. These roadmaps have provided and continue to provide 

valuable guidance to NIST laboratory research programs for assessing future directions 

of the photonics industry as a whole. 

b) ATP 

In addition to the NIST laboratories, the ATP also has a history of close interactions with 

the OIDA, with several ATP staff routinely both attending OIDA meetings and 

workshops and giving presentations. Because the OIDA intersects such a large 

percentage of the U.S. photonics industry, ATP outreach activities at OIDA meetings 

provide an excellent mechanism for alerting large segments of the photonics industry to 

the existence of ATP as a potential funding source for cutting edge technology 

development. 

E. NIST Laboratory Research Opportunities

There are several groups at NIST that are working on areas identified as near-term or 

long-term needs for SSL. In addition, there are other groups that could use their expertise 

in microelectronics to address similar issues in photonic semiconductor systems and 

24
devices. In the outline below, we highlight some of the topical areas important in SSL 

that scientists at NIST could address for both the near term, i.e., one to five year period, 

and the long-term, i.e., five to ten year time frame. 

1. Inorganic devices 

- Large area substrates, buffer layers and wafer research 

i. Uniformity 

1. Across wafer uniformity 

2. Wafer to wafer uniformity 

a. Strain at buffer/substrate interface 

b. Surface finish and structure 

ii. Defect structure 

1. Defect identification 

2. Cluster behavior 

- High-efficiency semiconductor materials 

- Reliability and defect physics for improved emitter lifetime and 

efficiency 

i. Defect identification 

1. Sources 

2. Effect on multilayer structures 

ii. Reliability 

1. Failure mechanisms

2. Lifetime prediction 

- High-efficiency phosphors and conversion materials 

i. Quantum efficiency 

ii. Reliability 

1. Thermal effects 

2. UV bleaching 

3. Degradation processes 

iii. Distribution of conversion material 

iv. Interface scattering 

- Encapsulants and packaging materials 

i. Interface scattering 

ii. Reliability 

1. Thermal damage 

2. UV damage

3. Degradation processes 

- Electrodes and interconnects 

i. Adhesion 

ii. Local heating 

- Measurement metrics and human factors 

i. Standards development 

ii. Color assessment 

1. Device inter-comparison 

2. Interface with human expectations 

25
- Physical, chemical, optical modeling measurement, and 

experimentation for substrate and epitaxial processes 

i. Efficiency 

1. Self absorption 

2. Interface scattering 

ii. Mechanical loading 

1. Lattice mismatch effects 

2. Thermal loading 

a. Distributed 

b. Local 

3. Delayed failure 

iii. Chemical stability of very thin films 

iv. Index measurement 

- Evaluate systems lifetime and performance characteristics 

i. Lifetime prediction 

1. Failure mechanisms

a. Static and cyclic electrical and thermal loading 

b. Defects 

i. Perturbing effects 

ii. Generation and coalescence 

ii. Quantum efficiency degradation 

1. Over time 

2. At high current 

iii. Color control 

2. Organic specific 

- Substrates for electro-active organic materials research 

i. Improved work function 

ii. Increased charge injection 

- High-efficiency, low voltage, stable materials 

i. Increased mobility 

ii. Increased light generation 

1. Reduced non-radiative recombination 

2. Enhanced reliability 

a. Thermal stability 

b. UV/blue degradation resistance 

c. Reduced sensitivity to water degradation 

- Improved understanding of fundamental physics 

26
III. PHOTONICS IN HEALTHCARE 

A. Current Status 

Although our understanding of both photonics and biology has made tremendous 

advances in the last few years, optical techniques have been used in healthcare 

applications throughout human history. From cave drawings that image deadly wounds 

via drawings of figures with arrows protruding from their bodies through descriptions of 

plague-generated lesions during the Middle Ages and the development of the optical 

microscope, optical techniques have been used to diagnose health problems and to 

monitor the progress of healing. 

In light of the extensive history relating optical approaches to health monitoring and 

diagnosis, a comprehensive discussion of the entire range of optical techniques currently 

used in healthcare lies outside the scope of this document. Rather, we will focus on 

recent developments in which optical techniques are used in new ways as diagnosis, 

treatment, or monitoring tools. While many of these tools are associated with aspects of 

imaging, photonics approaches should not be considered as synonymous with imaging. 

As will be discussed, photonic tools are being developed for treatment and chemical 

diagnosis as well as for imaging. In this section we will address both techniques already 

being developed for clinical applications and approaches still restricted to the laboratory

environment. The expectation is that many of the latter approaches will soon make the 

transition to clinical application as commercialization efforts mature. 

Before the discussion of specific applications, it should be pointed out that, like all tools, 

optical techniques have both benefits and limitations (Table 3). In practice, most of the 

benefits and limitations are application specific. For example, surface applications 

TABLE 3: Benefits and limitations of optical techniques 

Benefits: 

• Non-contact 

• Multiple wavelengths

- Variable penetration 

- Tunable absorption 

• Micrometer resolution 

• Morphological and chemical information possible 

• Combine imaging/treatment into same instrument 

Limitations:

• Limited penetration 

- Maximum penetration 10 cm in 

 IR region 

- Maximum penetration occurs for minimum 

resolution 

• Contrast agents required 

27
of optical techniques, i.e., those for the skin or eye, can usually be viewed as noncontact. However, for internal imaging, the limited penetration depth of optical 

techniques usually requires optical probes to bring the source light into the region to be 

interrogated, thus losing the non-contact aspect. Similarly, without the use of probes, the 

benefits of variable wavelength range are limited; typically, to achieve greater 

penetration, specific wavelengths are used, thereby pre-determining resolution and 

optical interaction with features of interest. Conversely, tuning the interrogation 

wavelength to interact with a specific feature of interest automatically places restrictions 

on the possible penetration depths. If the applications are intended to be used for 

diagnosis in vitro rather than in vivo, these restrictions are considerably relaxed, since 

penetration depth is less of an issue. 

1. Clinical: 

The development of lasers and light emitting diodes has had a major effect on medical 

treatment. From retinal mapping, eye surgery and epidermal ablation to more prosaic 

hair removal, lasers are routinely used for a range of surface medical treatments. 

Concurrent development of optical fibers has led to internal imaging capabilities such as 

endoscopy, permitting inspection of intestinal and esophageal passages to detect 

cancerous and precancerous conditions, and laparoscopy, allowing examination of 

abdominal and ovarian cavities. Combining laser sources and fiber catheters has given 

rise to capabilities such as laser angioplasty, in which plaque deposits are destroyed by 

focused optical radiation. In addition to these techniques, major advances in the 

understanding of cell chemistry for both healthy and diseased cells have resulted in 

increasingly sophisticated spectroscopic analyses of blood and tissue samples. In vitro

tools are currently being used for a variety of applications: e.g., to check glucose levels 

for diabetes monitoring, to detect troponin T and myoglobin as a monitor for heart attacks 

in real time, using turbidimetry for distributed clot detection. 

2. Research and Development: 

Although the words in vivo and in vitro are used throughout the medical and biological 

communities, their precise meanings are somewhat context dependent. While in vitro

means “in glass”, i.e., in a laboratory setting, and in vivo means “in life”, i.e., in a living 

body, the distinction is somewhat blurred. Some scientists consider studies of fixed cells 

to be in vitro and studies of living cells to be in vivo. In contrast, other scientists consider 

the study of living cells removed from a host to be in vitro, because they are in an 

artificial environment, and the study of cells in a living creature, e.g., mouse, human, to 

be in vivo. For this document, we use the latter definition; i.e., living cells that have been 

removed from their host are considered in vitro and not in vivo. 

a) In vitro 

While the predominant goal for research into biophotonics is the development of tools to 

be used eventually in vivo for healthcare,12 there are a number of technical advances that 

28
will almost certainly be limited to in vitro applications but that, nonetheless, will provide 

new understanding of life processes. This understanding will include both the behavior 

of healthy tissue as well as cellular and sub-cellular behavior associated with the onset of 

disease. The results of such an understanding could lead to the development of in vivo

tools and procedures for identifying and treating diseases such as cancer at the very onset 

of cellular damage, i.e., low grade dysplasia. For the in vitro research areas, photonic 

activities are divided into three components: Optical Microscopy, Spectroscopy, and 

Combinatorial approaches. 

i. Optical microscopy: 

Advances in optical microscopy have made it possible to image features on the 100’s and 

even 10’s of nanometer scale. Taking advantage of the nonlinear optical properties of 

biological material, in some cases new techniques have been able to make use of contrast 

mechanisms that do not require dyes or external tracers. In other cases, optical tracers 

that are designed to attach to specific cellular sites, providing optical contrast through 

mechanisms such as fluorescence provide information regarding cellular dynamics. 

Finally, optical tools have been developed that allow manipulation of cell components on 

the micrometer and sub-micrometer level. While most of the tools that use these 

techniques can be purchased from commercial vendors, new applications are continually 

being devised and reported. The following is an overview of optical microscopy 

procedures being developed specifically directed towards healthcare. 

- Confocal microscopy: This technique is a commercially available instrument that 

varies from traditional microscopy in that a scanned, focused laser beam and a 

pinhole spatial filter are used to provide high resolution both in the plane of the 

image and perpendicular to the image (i.e., in the axial direction). The principle 

advantage of the technique is that high resolution in the axial direction allows 

sequential images to be made at different focus depths into the specimen. 

Available software is able to combine these sequential planer images to generate a 

three-dimensional image. 

It has been shown that the lateral resolution and axial resolution of confocal 

microscopy can be λ/3.7 and λ/1.2, respectively, where λ is the wavelength of 

light used to generate the images.13 A disadvantage of the confocal microscope is 

that, while the pinhole in front of the detector provides spatial filtering for the 

light scattered from the specimen, the light incident on the specimen has no depth 

filtering. Therefore, scattered light at any depth that is aligned along the optical 

axis co-axial with the pinhole is convolved into the raw image, generating noise 

and reducing resolution.14 Numerical deconvolution procedures can, in principle, 

enhance this resolution13 to the order of 100 nm, but require an additional step and 

inherently involve modifications to the original data. An additional limitation of

confocal microscopy becomes evident when fluorescent markers are used. 

Because the energy required to excite the fluorescence must be greater than the 

energy of the excited photon, the source wavelength must be shorter than the 

wavelength of the excited photon. However, photon scattering and concomitant 

signal loss increase with decreasing wavelength. Therefore, while confocal 

29
techniques can generate 3-D images of fluorescing sites, the depth within the 

specimen from which the information is obtained decreases as the energy of the 

fluorescent photon increases. 

Figure 3: Schematic of a confocal microscope. The spatial filter in front of the detector provides

resolution. Three-dimensional images can be generated by scanning the specimen at different 

focus positions within the specimen. 

- Multi-photon imaging: In this procedure, which is increasingly seeing use in 

research laboratories for both basic research and pharmaceutical development, 

fluorescent markers are excited by the simultaneous absorption of multiple, lower 

energy photons from the excitation source. Usually, the markers and the 

excitation source are chosen such that two photons are adequate (i.e., the sum of 

the energies of the two photons is enough to excite the fluorescence), although 

there is recent work investigating three photon imaging.15 The probability of twophoton capture by the marker is reduced by about a factor of 106

 from the 

probability of single-photon capture for equivalent total photon energy.15 The 

probability of three-photon capture is down by an additional factor of 10. In order 

to obtain the high photon flux required to achieve multiphoton excitation, a wellfocused, mode-locked (e.g., femtosecond) laser is used as the source. Specimen 

damage due to the increase in laser flux is reduced by three effects: 1) the laser 

pulse width is very short, and, consequently, the average power is low, 2) the 

30
longer wavelength of the exciting laser is not efficiently absorbed by the 

specimen, and 3) the region of high flux is limited to the focused beam waist. 

Use of a multi-photon system results in very narrow depth resolution without 

many of the problems associated with normal confocal microscopy. The 

advantages of multiphoton imaging derive from the fact that no fluorescence will 

occur in the absence of simultaneous multiphoton absorption and the probability 

of that occurring goes as the fourth power of the intensity. Consequently, signal 

intensity resulting from excitation occurring before or after the focal spot will be 

negligibly small compared to the signal from the focus. Therefore, a major 

source of noise in confocal microscopy is eliminated in multi-photon 

microscopy. 

An additional opportunity for multi-photon imaging takes advantage of both twophoton and three-photon absorption. If two markers are used in the cell, one that 

requires two-photon absorption and one that requires three-photon absorption, two 

separate portions of a cell can be monitored simultaneously and potentially, 

interactions can be observed in real time. A disadvantage of multi-photon 

microscopy is that the low absorption of the incident wavelength means that a 

background image (i.e., a non-fluorescing image) may not be visible for 

reference. 

Figure 4: Energy diagram of two-photon process. Excitation wavelength is longer that emitted 

wavelength; a single incident photon has insufficient energy to excite an electron and is not 

absorbed. 

- Second- and third-harmonic generation:14-18 While higher-order harmonic 

generation has been studied in the photonics community for many years, its 

31
application to biological systems is still limited to basic research applications. 

The process involves incident light interacting with a material having nonlinear 

optical properties, resulting in a conversion of the incident light frequency to a 

higher harmonic value. The technique is, in some ways, superficially similar to 

multiphoton absorption although the physical principles involved are quite 

different. The apparent similarities arise because, in both cases, the light from the 

specimen areas of interest is at a different wavelength than the incident light and a 

combination of second- and third-harmonic generation, like a combination of twophoton and three-photon absorption, can result in different portions of the 

specimen being imaged by different wavelength light simultaneously. However, 

in second- and third-harmonic generation, the change in wavelength results from

optical nonlinearities in portions of the specimen itself rather than excitation of

fluorescence. In addition, for second- and third-harmonic generation microscopy, 

the incident light can generate an image of the portions of the specimen that do 

not generate higher-order harmonics. Another advantage of this procedure is that 

it does not require the presence of dyes or other markers that have potential 

viability consequences in the specimens. A disadvantage is that the specimens 

themselves must inherently have non-linear optical properties. However, a wide 

range of biological structures generates higher-order harmonics: e.g., cell 

membranes, muscle fibers, and nerve fibers.17,18 

Figure 5: Incident light on the nonlinear region results in scattered light at twice (2nd harmonic) 

or three times (third harmonic) the frequency of the incident light. 

Another issue that may limit the applicability of this technique is that higher-order 

harmonic generation in materials typically requires high incident flux. This can 

be achieved in a manner similar to the multiphoton absorption approach by using 

32
a microscope objective to focus the incident light into a small volume at the 

region of interest. However, unlike the multiphoton absorption approach, which 

uses an incident wavelength that is not strongly absorbed, the higher harmonics 

approach requires strong interaction between the material and the incident 

wavelength. Therefore, care is needed to avoid photo-damage to the specimen. 

- Fluorescence resonance energy transfer (FRET): FRET is a microscopy 

technique widely used in cellular biology research – both basic and applied. The 

technique uses two fluorescent markers and a laser source to image interactions 

between cellular components (e.g., two different proteins) on the nanometer 

scale.19 One cellular component is tagged with one fluorophore and a second is 

tagged with the second fluorophore. The wavelength of the laser source and the 

optical properties of the two fluorophores are carefully chosen such that the laser 

wavelength, λl, will excite fluorescence λf1 in the first fluorophore but will not 

excite the second fluorophore. However, when the two fluorophores are close 

enough together, a resonant energy transfer will occur between the excited first 

fluorophore and the non-excited second fluorophore resulting in fluorescence 

from the second fluorophore at λf2 and a decrease in the intensity of λfl. 

Monitoring the intensity of λfl and λf2 during an experiment provides information 

regarding the conditions affecting interactions between the two cell components. 

Figure 6: Schematic of FRET. As the two particles approach each other, the laser-induced

fluorescence in the dye in particle 1 induces a secondary fluorescence in the dye in particle 2

through non-radiative dipole interactions.

The primary advantage of FRET is its extreme sensitivity to the spacing between 

fluorophores. Because the energy transfer is a non-radiative resonance phenomenon, it is 

very short range and the efficiency of the transfer is strongly dependent upon the 

separation between the cell components. Measurements of the intensity of λfl or λf2 can 

33
give very precise information regarding that separation; monitoring the polarization of 

the emissions can give information regarding relative orientations. A disadvantage of the 

technique is that interactions between cell components must be inferred and the type of

interaction is unknown. In addition, the effects of the fluorophores attached to the 

components on their subsequent interactions are unknown. 

- Total internal reflectance (TIR): TIR is being developed to provide images and 

information in very restricted regions of a cell. The technique involves placing 

the region of interest, e.g., a cell membrane, very near a planer waveguide. As 

light is transmitted through the waveguide, interactions between elements near the 

membrane can interact with the evanescent waves leaking from the waveguide; 

because the interactions are with evanescent waves, they are strong functions of 

their distance from the waveguide.20 Typically, luminescent tags are attached to 

the cell components of interest and interactions are inferred from the intensity and 

distributions of the luminescence sites. Many of the advantages and 

disadvantages of this technique are similar to those discussed for FRET. 

Figure 7: Schematic of TIR fluorescence 

- Near-field scanning optical microscopy (NSOM): NSOM provides nanometer to 

tens of nanometer lateral resolution through the use of the illuminating aperture, 

e.g., a drawn optical fiber, being placed within nanometers of the specimen 

surface. Under these conditions, i.e., both the separation of the light source from

the specimen and the dimensions of the illumination aperture are much less than 

the wavelength of the illuminating light, the resolution is defined by the aperture 

size. While NSOM is an increasingly widely used technique in materials, there 

are a number of difficulties associated with using it for biological specimens,21

either fixed, i.e., treated with chemicals to generate a rigid, cross-linked structure, 

or living. One problem is that biological specimens are not flat on the nanometer 

scale. Consequently, maintenance of the spacing between the illumination 

aperture and the specimen can be quite difficult as the specimen is scanned. A 

34
similar issue is that biological specimens are not thin on the nanometer scale and, 

in addition, biological cells are usually filled with water. Therefore, the feedback 

forces required to position the NSOM can drive objects of interest out of the field 

of view in living cells. NSOM can, in principle, be combined with spectroscopic 

techniques such as fluorescence (e.g., FRET) techniques22 or Raman 

spectroscopy

23 to provide additional information. However, the low light levels 

in NSOM make spectroscopy challenging, particularly for Raman measurements, 

which are inherently inefficient. 

 

- Fluorescent markers: Frequent reference has been made above to optical tracer 

and fluorophore tags in the various optical microscopy techniques. Materials such 

as fluorescent particles,24 fluorescent proteins25 and quantum dots26,27 have been 

and are being developed that will attach to specific proteins or other cellular 

features to provide a signal for optical microscopy. Issues associated with similar 

tracers for a wide range of in vivo applications will be mentioned later. On the 

cellular, in vitro level, these tracers are now making it possible to monitor timedependent processes in living cells. However, the questions of toxicity, 

specificity, and more subtly, whether the biological functions are modified by 

perturbations due to the attached materials remain unanswered and objects of 

concern.28,29 

 

- Optical manipulators: Although not limited to optical microscopy, a couple of 

recently developed optical tools used in microscopy should be mentioned: optical 

scalpels30,31 and optical tweezers.32 Optical scalpels are focused laser beams used 

to cut biological tissue. Although this is not a new idea, it has in recent years 

been extended to microsurgery on, and within, individual cells. Lasers are being 

used to open and reseal cell membranes, liposome membranes, and even human 

chromosomes.33 This ability would be of limited use without the simultaneous 

development of tools like optical tweezers. Optical tweezers use forces generated 

by the electric field gradient of a focused laser beam to entrap and move small 

particles. The particles can range from a few nanometers to several micrometers. 

This size range makes optical tweezers an excellent tool for moving biological 

components within a cell, e.g., the nucleus, or even the cells themselves. The 

combination of optical scalpel and optical tweezers makes it possible to insert or 

remove material from within cells or within organelles, to attach components, 

e.g., proteins, onto other cell components, and even to dissect macromolecules 

within cells.

ii. Spectroscopy: 

A number of the techniques mentioned above are powerful tools that can provide much 

more information than is contained in optical contrast images. For example, Raman, 

near-field Raman, fluorescence, and light scattering measurements can all be used 

spectroscopically, i.e., as a function of wavelength, to provide chemical, orientation, and 

structural information in addition to the time-dependent location information that images 

provide. The combination of spectroscopic information with imaging information has 

the potential of providing detailed information regarding intercellular and intracellular

35
mechanisms under varying conditions. Currently, however, spectroscopic tools are 

predominately used independently of imaging techniques in their traditional role of

performing chemical assay, albeit at increasingly reduced size scales. Sample sizes are 

being reduced to μliters, and under carefully controlled laboratory conditions, even single 

molecules have been interrogated. 

iii. Combinatorial approaches: 

The enhancement of spectroscopic techniques that allows single cell or even sub-cell 

interrogation makes it possible for researchers to apply parallel measurements to reduce 

noise34 or quickly to evaluate new markers or drugs under differing conditions.35,36 One 

of the easiest approaches is to use optical fiber arrays, applying separate fibers to 

individual cells. In this way, identical measurements can be made simultaneously on 

identical cells to reduce noise within a measurement, or individual cells can be modified, 

e.g., to contain a different marker or modification of a drug, and a wide parameter space 

can be mapped rapidly. The measurements can be as simple as monitoring fluorescence 

intensity or as sophisticated as measuring entire Raman spectra for each fiber. An 

alternate approach that does not require fibers could make use of uniform illumination of

an array of cells or sub-cellular components. The scattered light from the specimens 

could then be individually imaged, via an array of micro-lenses, onto an array detector, 

or, alternatively, the light could be scanned rapidly into a single detector. All of these 

approaches have the advantage of high-speed assessment capability. However, there are 

also limitations. The major limitation is spectroscopic techniques provide a great deal of 

data on each cell but there is currently no mechanism for rapidly quantifying, 

assessing, and efficiently accessing all of the chemical and structural information 

obtained for each element of the array when a large array of data is being obtained 

with rapid throughput.

12 Therefore, while in principle a great deal of knowledge could 

be obtained regarding marker or drug interactions within a cell under various conditions, 

typically such data are not obtained. Rather, a spectroscopic peak is chosen and its 

intensity, position, or width is monitored for each element of the detector array and the 

remaining data are discarded.37 This leads directly to the second limitation of the 

technique. The procedure requires a precise knowledge of the type of interaction to be 

investigated. Without this knowledge, simultaneous relevant processes that occur may 

not be detected. 

 

b) In vivo 

Challenges associated with in-vivo measurements are of a different nature than those 

found in in-vitro work. In particular, the primary goal of in-vivo research is to develop 

procedures that will not generate more damage in the host than the intended treatment 

cures. The second goal is to generate sensing schemes that will detect specific responses, 

via imaging or chemical sensing techniques, in an inhomogeneous environment that has a 

36
Figure 8: Flowchart showing sequential, semi-independent relationship between diagnosis,

intervention/treatment, and treatment evaluation in current medical practice. 

dynamic background filled with a wide range of chemical species, pH values, densities, 

sizes, and optical properties. The third goal is to improve understanding of the 

interworkings of the living system, thereby developing criteria for earlier, more precise, 

disease indicators and minimizing the extent of required medical interventions. Current 

procedures generally use a chemical test or some form of an image to detect a problem, 

then, if feasible, an image to localize the problem, a medical intervention, and finally, an 

image or chemical test to evaluate the consequences of the intervention (see Figure 2). 

Consequently, we will divide the following discussion into the categories of Imaging, 

Diagnosis, and Treatment. 

i. Imaging: 

Because of the difficulties listed above, a living body is a very difficult object in which to 

discover defects via photonic imaging. Problems are minimized to some degree in 

procedures such as x-ray imaging of bone, because the penetration of the x-rays is 

relatively high in a living creature and the contrast between the high density, high atomic 

number (i.e., high capture cross section) bone and the low density, relatively low atomic 

number soft tissue allows for good signal intensity and reasonable high contrast. 

However, use of visible optical techniques to obtain images is much more difficult. 

Water and hemoglobin in the body combine to absorb light over the entire near-UV to 

near-IR range38 with the exception of two windows centered at approximately 800 nm 

and 1200 nm. In these windows, light can penetrate about 12 cm. However, for 

wavelengths of 700 nm, 600 nm, or 500 nm, the penetration depths resulting in half the 

initial intensity are 10 cm, 1 cm, and 0.5 cm, respectively (see Figure 3). Clearly, there is 

a trade-off between resolution and penetration depth, with penetration depth falling off 

dramatically as wavelength decreases. However, absorption is only one of the factors 

governing the use 

37
I/I0 = 0.5

0

2

4

6

8

10

12

14

400 500 600 700 800 900 1000

Wavelength (nm)

Penetration (cm)

Figure 9: Penetration depth through water and hemoglobin across the visible wavelength range. 

Values represent the depth at which the intensity is 50% of the original value. 

of visible or near visible optical techniques in vivo. The second major limiting factor in 

using optical techniques is that bodies are highly heterogeneous systems, filled with 

scattering objects ranging in size from tens of nanometers, e.g., membranes, to objects 

such as organelles and whole cells on the tens of micrometers scale. Consequently, even 

in the absence of absorption, reflected and transmitted signals are highly attenuated due 

to multiple scattering events at all wavelengths. Finally, living bodies are not static. 

Muscles twitch, blood flows, chemical processes occur. Therefore, any optical technique 

used in-vivo must be designed to accommodate such motion, or else must be limited to 

detection of defects large compared to the scale of motion-induced displacement. 

- Optical scattering One of the most rudimentary spectroscopic tools is the 

measurement of transmission as a function of wavelength. However, because of 

the heterogeneous nature of a biological body, and the wide size scale over which 

the heterogeneous features occur, as mentioned above, scattering of the incident 

light is impossible to avoid. Consequently, the use of transmitted light to image 

internal objects such as tumors has not been pursued in the past. However, with 

the advent of better near-IR sources, detectors, more powerful computers and, 

especially, models that incorporate detailed descriptions of how different 

wavelengths interact with tissue, optical scattering techniques are beginning to be 

developed for internal diagnosis applications.39 Even with improved theory and 

measurement procedures, absorption and scattering lower the signal intensity and 

reduce contrast to the point that lesions/tumors below 5 mm are difficult to detect. 

However, on the positive side, the use of multiple wavelengths allows 

spectroscopic information to be obtained. Consequently, information regarding 

different components that make up the body, e.g., water, hemoglobin, and lipids, 

can be acquired through multiple scattering measurements. 

38
- Fluorescence As discussed previously, advances in fluorescence techniques 

already provide extraordinary insight into cellular reactions in the lab and hold the 

promise for making similar contributions as diagnostic and health monitoring 

tools in vivo. Use of fluorophores such as fluorescent particles,24 proteins25 and 

quantum dots26,27 that can be targeted toward specific proteins, organelles, or, 

within a body, specific organs, inflamed joints,40 or tumors opens tremendous 

opportunities ranging from basic research into cell behavior and chemistry 

through applications in diagnostic and treatment monitoring. In addition, the 

increasing possibility for development of new markers that identify the onset of

diseases afflicting specific subset populations holds the promise of “personalized 

medicine”. Primary challenges to this vision are difficulties associated with 

developing a wide array of biomolecular tracers for the different possible 

applications. Not only are there difficulties associated with each tracer creation, 

i.e., the identification of a tracer as well as the associated reliability, specificity, 

and failure mechanisms, and increasing awareness of toxicology issues, but, as 

medical diagnosis tools become increasingly directed toward smaller population 

sizes, the cost of such tracers must be borne by a continually decreasing number 

of individuals. The tradeoff between cost and population is already affecting 

diagnostic tracer development.41 A separate issue that needs to be addressed for 

fluorescent imaging in vivo is the need for improved resolution. Whereas 

resolution in vitro can be sub-micrometer, in-vivo resolution is many centimeters 

or, at best, many millimeters. As better understanding of cell chemistry makes 

possible disease detection at earlier stages, the resolution limitations of 

fluorescence imaging will have to be improved for the improved knowledge base 

to result in a decrease in the severity of medical intervention. 

- Optical coherence tomography42-46 (OCT) Optical coherence tomography is an 

imaging tool that provides high lateral and depth resolution. The technique uses 

an interferometer with a moving reference mirror to obtain depth information. 

Depth resolution is inversely proportional to the band width, so a low time 

coherence light source such as a superluminescent optical diode is typically used 

as a light source. The resultant high resolution is one of the principle benefits of 

OCT, which is able to provide sub-cellular information even in vivo. Developed 

initially for inspection of the eye, OCT procedures are being developed that will 

extend the technique to the esophagus and even the circulatory system. The eye, 

containing a transparent portal, allows OCT interrogation of several millimeters. 

However, in other applications, penetration depths are limited to a millimeter or 

less. The limited penetration poses the most critical limitation on OCT. While 

OCT has the resolution and the spectroscopic capabilities to detect the onset of 

lesions at a very early stage, it can only see surface or near-surface features. The 

second important limitation of OCT, paradoxically, is related to its high 

resolution. OCT gathers so much information on such a fine scale that: 1) it is 

difficult to sort through all of the data and 2) it is difficult to identify the precise 

location in the body at which medical intervention (e.g., a surgical tissue removal) 

is needed. At this time, there is no known solution to the penetration depth barrier 

to OCT. However, the “data glut” problem is being investigated with a multi39
modal approach that combines OCT with another imaging tool of lower 

resolution. The alternate imaging tool can scan the area, and when an indication 

of a potential problem is observed, the OCT can be used to conduct a high 

resolution scan of a limited area. Alternatively, both scans can be conducted 

simultaneously and the lower resolution tool can be used to register the location 

of the OCT data. 

 ii. Diagnostics: 

Optical tools in use or being researched for in vivo diagnostics typically fall into one of 

two categories: imaging47 or spectroscopy48. Imaging, by far the most widely researched 

aspect of optical diagnosis techniques, is used, often with disease or organ specific 

tracers, to generate high contrast images for diseases detection and concomitant size and 

location information. By making measurements over time with a contrast agent or 

molecular tracer, relative severity of the disease can sometimes be assessed. However, 

the information is typically visual only and, consequently, relatively qualitative in nature. 

Spatial dimensions can be obtained but detailed information will still have to be 

determined by a biopsy. Spectroscopy tools, i.e., tools used to obtain chemical 

information rather than images, are being recognized as potentially very powerful for invivo applications but are still relatively rare. As mentioned previously, when 

spectroscopic tools are used for imaging, e.g., fluorescence or Raman spectroscopy, 

typically a major peak position or intensity is monitored and the remaining information is 

discarded for processing speed and data storage reasons.37

iii. Treatment: 

As might be expected, photonic tools in medical treatment lag behind those being 

developed for imaging and diagnostics. One treatment with potentially broad 

applications is photodynamic therapy (PDT). In PDT, light sensitive agents, e.g., 

systemic photosensitive dye, quantum dots (QDs), nanoscale spheres, collect at a region 

of interest such as a tumor. A laser or high intensity diode lamp illuminates the region

either locally activating a toxin or generating local heating that kills the surrounding 

tissue. Although the technique has clear benefits, there remain a number of issues that 

must be addressed. First, monitoring the dosage of the optically active agents relative to 

the dosage49 required for treatment in absolute terms and as a function of time is difficult. 

Second, systemic dyes are undesirable because the patient remains light sensitive until 

the body eliminates the dye, which can take several hours or even a few days for 

complete elimination. Third, as mentioned previously, the material composing most QDs 

is toxic. The QDs can be coated but the lifetime and reliability of the coating in the 

chemically active environment of the body as well as during optical heating must be 

ascertained. Nanoscale spheres made of Au, alumina, or polymers are more inert, 

although the long-term biological response to these materials is not known. Equally 

important for all of the nanoscale materials is the fact that both their dispersal in the body 

and their optical absorption are strongly dependent upon sphere size. Therefore, material 

issues such as purity, size, size distribution, agglomeration, and reactivity must be 

controlled very well. 

40
B. Long-term issues 

Long-term issues associated with healthcare are predominately related to safety, 

reliability, efficiency, and effectiveness. In addition, there is a growing sense that the 

traditional distinctions between imaging/detection, diagnosis, and treatment will become

blurred in the future. Figure 4 shows schematically this blurring of previously 

independent aspects of medical treatment. As mentioned previously, current medical 

practice typically separates diagnosis, treatment, and evaluation into distinct categories. 

Frequently, practitioners in the three categories do not even speak together; written 

reports are passed between them or placed on the patient’s chart. Consequently, subtle 

effects in diagnosis or changes in treatment may not be communicated among the 

different groups of people, leading to confusion in treatment. Improvements in imaging 

and spectroscopic techniques are expected to provide true chemical information 

across the entire image and to provide it in real time. Such capabilities could lead to 

in-situ biopsies, real time analysis during intervention (e.g., surgery, PDT), and 

immediate post-treatment biopsies. Increased knowledge of the chemistries associated 

with precursors to disease coupled with spectroscopic imaging on the sub-cellular level 

might even allow detection, treatment, and follow-up of pre-cancerous areas without the 

need for traditional surgical procedures even arising. 

 

Figure 10: Schematic of future use of photonics in medical care. Advances in both imaging and 

spectroscopy procedures will a linking of the formerly distinct areas of Diagnosis, Treatment, and 

Evaluation into a more monolithic structure. As spectroscopic imaging tools improve to allow 

chemical analysis across entire images, distinctions between imaging and chemical tests will tend to

disappear, as well. 

41
1. Implant/biotracer/imaging agent issues: 

The long-term issues associated with insertion of foreign material into the body are 

similar to those discussed above for short-term tests. The primary concern is for 

biocompatibility.12 What are the degradation mechanisms?

50 What occurs at the 

interface between the body and the implant? What time frames are important? What are 

the failure probabilities and implications? Are there fouling mechanisms that need to be 

considered? With nanoparticle tracers, the time frame in the body is intended to be on 

the order of hours or days. Yet, some of the nanoparticles may become trapped and 

remain indefinitely. For those materials and their debris, the toxicity issues touched on 

previously remain important, and moreover, the time frame over which interactions must 

be considered is extended considerably. Some of the parameters that need to be 

monitored for toxicity assessment are:51 composition, size, shape, deformability, stability, 

and coatings. 

2. Imaging/spectroscopy: 

As shown in Fig. 4, a long-term goal for imaging is to combine real-time spectroscopic

information with image formation. Implied in that goal is the need to develop a direct 

relationship between measurements and cellular behavior.37 A second critical long-term

need for imaging that is expressed by everyone from the pharmaceutical industry through 

diagnosticians, all the way to the FDA is the need for standards, procedures, and 

techniques that will provide validated image interpretation.52 Among the necessary 

improvements are instrument-to-instrument reproducibility, operator-to-operator 

reproducibility, and even reproducibility of the same operator on the same instrument and 

the same patient from one measurement to the next.40 In fact, there appears to be a 

widespread sense that image analysis tools need to be developed to the extent that the 

judgment of the human operator can be removed from the image analysis process.40,52 

This goal implies that interactions of the physics, chemistry, biology, and statistics used 

to create the image need to be more rigorously understood to allow automation of image 

analysis.12 Combining these requirements, the future of imaging requires, on its simplest 

level, that: 

1. the engineering of the instrumentation must be well enough defined that images 

made of standard reference specimens on instruments from different 

manufacturers or different models from the same manufacturer can be related 

in a meaningful and understandable way; 

2. analysis algorithms must provide at least a core set of imaging tools common to 

all instruments to allow image comparisons between instruments and to 

confirm consistency 

and on a more sophisticated level, that: 

1. the image probe should provide cellular and sub-cellular chemical information; 

2. the information should be directly connected to cellular processes of interest; 

3. the information should provide quantitative information regarding the presence or 

absence of a disease and, if present, a measure of the disease progress. 

42
The implications of the last three items are that detailed spectroscopy information 

needs to be obtained as part of the image. This, in turn, requires that spectroscopic 

techniques need to be improved in speed, signal/noise, and spatial resolution for them to 

be useful as imaging tools on the cellular level while retaining their use as spectroscopic 

instruments. 

In addition, because these data sets will contain three-dimensional coordinate 

information, spectra containing up to 1000 points of wavelength versus intensity (and 

possibly phase) information, possibly a temporal axis, and fitting parameters, data 

handling tools need to be developed to optimize data storage, data retrieval, and data 

viewing, as well as general data manipulation for n-dimensional data sets. Finally, data 

analysis techniques need to be standardized and automated. While relatively large, 

isolated peaks can be fitted automatically with reasonable accuracy, analysis of 

complicated spectra still requires operator input and judgment. This last statement leads 

to a point only recently recognized; all image analyses should include quantitative, 

standardized, and well-defined uncertainty discussions and medical practitioners need to 

be trained to understand those discussions. 

C. NIST Interaction Opportunities in Photonics in Healthcare

Unlike SSL, which is predominately a commercial driven activity that also has benefits to 

society at large in terms of increased energy efficiency, increased reliability, and 

reduction in greenhouse gas production, healthcare is viewed as primarily a matter of 

public safety and only secondarily as a commercial enterprise. Consequently, the area of 

photonics in healthcare is dominated by government agencies tasked with the 

responsibility of assuring safety and effectiveness of medical treatment and is less driven 

by large consortia of businesses. This is not meant to imply that business does not play a 

large role in healthcare in the United State, from large pharmaceutical companies down to 

small start-ups, nor does it mean to downplay the importance of university research, 

particularly those universities with associated teaching hospitals, in medical R&D. 

However, for the subject of Photonics in Healthcare, unlike SSL, it is difficult to isolate 

one or two consortia that drive research directions and guide government agencies that 

monitor this topic. Rather, two government agencies, the National Institutes of Health 

(NIH) and the Food and Drug Administration (FDA) function as the primary drivers for 

progress through their funding and regulatory practices. These two organizations act as 

the main mechanism for research concepts and devices to reach commercialization. A

third organization, the National Science Foundation (NSF) provides funding for research 

that is typically less applied. 

 

1. Food and Drug Administration (FDA) 

The FDA is a regulatory agency that monitors medicines, devices, and procedures for 

safety and compliance with regulatory requirements. Its mission involves assuring nearterm and long-term safety and research conducted at the FDA is closely focused on this 

mission. 

43
a) NIST Laboratories 

Most of the work at the FDA is too applied and too near term for research collaborations 

between NIST and FDA to be easily formed. However, some areas of mutual concern

are readily apparent; the FDA is highly concerned with reliability, degradation, 

degradation mechanisms, and lifetimes associated with any foreign material implanted or 

injected into the body. There are many materials and chemistry issues that could 

reasonably be addressed by NIST. In addition, there are a number of areas (e.g., OCT) in 

which the FDA would benefit from standards work and metrology that could be done at 

NIST. It should be noted that, because of the large level of device, drug, and treatment 

monitoring which is the ongoing responsibility of the FDA, external collaborations need 

to be directly related to the FDA mission. 

b) ATP 

The FDA could provide a large reservoir of reviewers, and potentially, ATP proposal 

evaluation board members who have an outstanding knowledge of current medical 

technology and associated barriers and pitfalls. The aspects of the FDA that make 

scientific collaboration somewhat difficult for the NIST laboratories (i.e., short term, 

applied research) provide the FDA scientists with an excellent view of needed 

improvements and recognition of innovative thinking regarding technologies soon to be 

introduced into the marketplace. 

2. National Institutes of Health (NIH) 

The National Institutes of Health are formed of a group of semi-autonomous Institutes, 

each of which has its own mission, typically, the study and treatment of a specific 

disease. Although most of these Institutes probably have applications that could be 

considered as biophotonics, it appears that bulk of the work on photonics in healthcare is 

funded by either the National Cancer Institute (NCI) or the National Institute for 

Biomedical Imaging and Bioengineering (NIBIB). 

a) NIST Laboratories 

Interactions with NIH benefit the NIST laboratories in three areas. First, NIH provides 

an important mechanism for generating collaborations between NIST scientists and the 

medical community, either NIH staff or researchers funded by NIH. This mechanism has 

been strengthened considerably by the joint NIST/NIH postdoctoral program. The 

second benefit of working with NIH is credibility. NIST is well recognized as a 

metrology laboratory but is not well known for its research in medical or biological 

applications. Therefore, collaborating with the medical staff at NIH provides that 

dimension of capabilities to the joint research. The third benefit is that proposals that 

advance both the health mission of NIH and the metrology mission of NIST can result in 

funding for equipment and guest scientists. It should be mentioned that there are a 

number of ongoing interactions between different groups at NIST and NIH. 

44
b) ATP 

Interactions with NIH benefit ATP in ways similar to those described for DOE in the SSL 

section. Not only does NIH form a source of potential reviewers for biology/health 

related ATP proposals, close relations with NIH provide insight into near-term and 

longer-term research and development issues associated with healthcare. In addition, it 

may be possible to develop a relationship with program managers at NIH in which they 

shepherd researchers who have commercialization proposals that are inappropriate for 

NIH funding toward ATP competitions. Finally, the NIH provides both the ATP and the 

laboratories an additional mechanism for outreach and education through the many 

workshops that the NIH provides on a wide range of current topics. 

3. National Science Foundation (NSF) 

The NSF is a government funding organization directed to providing resources for basic 

research. In this regard, the NSF might be considered on the opposite side of NIH from 

the FDA. The NSF is less concerned about commercialization than NIH and far more

concerned with expanding the basic knowledge base than the FDA is. 

a) NIST Laboratories 

Although the NSF does not provide funding for NIST staff time, it does fund proposals 

that would cover guest scientist, travel, and publication costs. More importantly, the NSF 

has a huge number of contacts with colleges and universities and, consequently, could 

provide a great deal of information that would lead to collaborations between NIST staff 

and universities. The NSF can also provide an additional resource: information regarding 

current research trends.

b) ATP 

As with other government agencies discussed previously, the NSF can provide reviewers 

for proposals. In addition, the NSF funds technology centers that act as incubators for 

new companies. Contact information for the NSF Center for Biophotonics Science and 

Technology is provided in Section VI: Appendix II. 

D. NIST Research Opportunities 

As mentioned above, there are a number of groups at NIST already involved in 

biophotonics research and active collaborations with NIH or other organizations. Some

of the research issues in the outline below are being addressed by these groups. 

However, the listed items remain important topics to enhance current understanding of 

biological behavior in general as well as specific instrument/biology interactions. In 

addition, many of the topics listed below address metrology needs and, consequently fall 

directly into the NIST mission. 

1. Imaging 

a. Resolution 

i. Signal/Noise (S/N) 

1. Physics of interactions

45
2. Statistical tools 

3. Uncertainty analysis

ii. Contrast 

1. Physics of interactions

2. Markers 

a. Sensitivity 

b. Specificity 

c. Toxicity (material properties) 

d. Uniformity 

e. Material/tissue interface chemistry 

b. Reproducibility 

i. Operator to operator 

1. Measurement protocols 

2. Technique metrology (e.g., OCT, fluorescence, Raman) 

ii. Single operator repeatability (same is operator to operator) 

iii. Instrument to instrument 

1. Measurement protocols 

2. Standard sources, detectors 

3. Calibration procedures 

c. Spectroscopy 

i. Spatial resolution 

ii. Relationship to biological functions 

iii. Sensitivity 

iv. Data handling 

2. Implants 

a. Biological compatibility

b. Reliability 

i. Degradation mechanisms 

1. Encapsulation 

2. Mechanical 

3. Chemical 

a. Interface interactions 

b. Particle/ion diffusion 

ii. Lifetime prediction 

iii. Accelerated test procedures 

 

3. Single cell investigation

a. Near field techniques 

i. Metrology 

ii. S/N 

iii. Apply to living cells 

b. Measurement physics relationship to biological function 

46
IV: REFERENCES 

1 NGL Industry Alliance Handout Sheet, Technology Demonstration, Washington, DC 

(9/11/2003). 

2 “Energy Savings Potential of Solid State Lighting in General Illumination 

Applications”, prepared for the Building Technologies Program, Office of Energy 

Efficiency and Renewable Energy, U.S. Department of Energy, Navigant Consulting, 

Inc., Washington, DC (11/2003) 

3 “The Promise of Solid State Lighting for General Illumination – 2002 Update”, 

Optoelectronics Industry Development Association, Washington, DC (2002). 

4 “New Release”, Cree Lighting News Release (2/8/2005) 

5 Brodrick, J. R., “DOE Solid State Lighting Status and Overview”, DOE Solid State 

Lighting Program Review, San Diego, CA (2/3-4/2005). 

6 “Energy Savings Estimates of Light Emitting Diodes in Niche Lighting Applications”,

U.S. Department of Energy (11/2003). 

7

Dowling, K. and Kennedy, S., Keynote Presentation, DOE Solid State Lighting Program

Review, San Diego, CA (2/3-4/2005). 

8 “Summary of Breakout Sessions Prioritization Results from Day 2: Update of SSL 

R&D Agenda”, DOE Solid State Lighting Program Review, San Diego, CA (2/3-4/2005). 

9 NEMA – Solid State Lighting, http://www.nema.org (12/10/2004). 

10“LUMILEDS, Light From Silicon Valley”, Nanoscience and Solid State Lighting, 

Department of Energy Nanosummit, Washington, DC (6/23 – 24/2004). 

11 Gottlieb, P, Solid State Lighting, Intellectual Property, DOE Solid State Lighting 

Program Review, San Diego, CA (2/3-4/2005). 

12 R.E. Swaja, Senior Science Advisor, National Institute of Biomedical Imaging, 

National Institutes of Health, private communication (5/5/2005). 

13 M. Schrader, S.W. Hell, and H.T.M. van der Voort, “Potential of Confocal 

Microscopes to Resolve in the 50 – 100 nm Range”, Appl. Phys. Lett. 69 #24 3644-3646 

(December, 1996). 

14 B. Schu, “Microscopy Researchers are Redefining their Images”, Genomics & 

Proteomics, www.genpromag.com, Reed Business Information, Morris Plains, NJ (March 

2005). 

15 D.W. Piston, T.J. Fellers, and M.W. Davidson, “Fundamentals and Applications in 

Multiphoton Excitation,” in Nikon MICROSCOPY, 

www.microscopyu.com/articles/fluorescence/. 16 T. Pons, L. Moreaux, O. Mongin, M. Blanchard-Desce, J. Mertz "Mechanisms of 

Membrane Potential Sensing with Second Harmonic Generation Microscopy" J. Biomed.

Opt. 8: 428-431 (2003). 

17 Shi-Wei Chu, Szu-Yu Chen, Tsung-Han Tsai, Tzu-Ming Liu, Cheng-Yung Lin, HuaiJen Tsai, and Chi-Kuang Sun, “In Vivo Developmental Biology Study Using Noninvasive 

Multi-Harmonic Generation Microscopy” Optics Express 11 #23 3093-3099 (2003). 

18 Chi-Kuang Sun, Shi-Wei Chu, Szu-Yu Chen, Tsung-Han Tsai, Tzu-Ming Liu, ChungYung Lin and Huai-Jen Tsai, “Higher Harmonic Generation Microscopy for 

Developmental Biology”, J. Struct. Biology 147 #1 19-30 (2004). 

19 R.M. Clegg, “The Vital Contributions of Perrin and Forster,” Biophotonics 

International 11 #9 42-45 (September, 2004). 

47
20 K. Hassler, T. Anhut, R. Rigler, M. Gösch, and T. Lasser, “High Count Rates with 

Total Internal Reflection Fluorescence Correlation Spectroscopy,” Biophys. J. LO1-

LO3 (2005). 

21 L. Goldner, Optical Technology Division, NIST, private communication (1/31/2005). 

22 J. Hwang, Optical Technology Division, NIST, private communication (5/16/2005). 

23 C.L. Jahncke and H.D. Hallen, “Near-Field Raman Spectra: Surface Enhancement, zpolarization, Fiber Raman Background and Rayleigh Scattering,” 9th Annual Meeting of 

IEEE Lasers and Electro-Optics Society 96 Conference Proceedings 1 176-177 (1996). 

24 K. Robinson, Fluorescent Nanoparticles Provide Single-Bacterium Detection,” 

Biophotonics International, 11 #11 23-24 (November, 2004). 

25 H. Hogan, “Fluorescence at the Flip of a Molecular Switch,” Biophotonics 

International 12 #1 34-38 (January 2005). 

26 H. Hogan, “Dialing in Quantum Dots,” Biophotonics International, 11 #9 27-28 

(September, 2004). 

27 K. Robinson, “Quantum Dot Coating Improves Specificity of Tumor Targeting and 

Imaging,” Biophotonics International, 11 #9 52-53 (September, 2004). 

28 private communication, NSF (3/24/2005). 

29 H. Hogan, “Differential Interference Contrast Microscopy Images DNA,” Biophotonics 

International, 11 #10 52-53 (October, 2004). 

30 D.S. Burgess, “Laser Microdisection: Making Inroads in Research,” Biophotonics 

International, 11 #9 46-49 (September, 2004). 

31 C. Les, “Violet Diode Laser Performs Cell Transfection,” Biophotonics International 

12 #3 26-27 (March 2005). 

32 S. Kulin, R. Kishore, K. Helmerson, and L. Locasio, “Optical Manipulation and Fusion 

of Liposomes as Microreactors,” Langmuir 19 #20 8206-8210 (June 2003). 

33 K. Konig, I. Riemann, and W. Fritzsche, “Nanodissection of Human Chromosomes

with Near-Infrared Femtosecond Laser Pulses,” Opt. Lett. 26 #11 819-821 (June, 2001). 

34 G. Boas, “Fiber Based Cell Array Sifts Through Genetic Noise,” Biophotonics 

International 12 #1 60-61 (January 2005). 

35 D. Walt, “An Array of Solutions,” oe magazine 5 #5 19-21 (May 2005). 

36 L.P. Choo-Smith, H.G. Edwards, H.P. Endtz, J.M. Kros, F. Heule, H. Barr, J.S. 

Robinson Jr., H.A. Bruining, G.J. Puppels, “Medical Applications of Raman 

Spectroscopy: from Proof of Principle to Clinical Implementation,” Biospectroscopy 67

#1 1-9 (January 2002). 

37 L. Esterowitz, Program Director, Division of Bioengineering & Environmental 

Systems, National Science Foundation, private communications (March, 2005). 

38 R. Weissleder, “A Clearer Vision for In Vivo Imaging,” Nature Biotechnology 19 316-

317 (April, 2001). 

39 A.E. Cerussi and B.J. Tromberg, “Optical Mammography Inches Closer to the 

Clinics,” Biophotonics International 10 #11 38-42 (December, 2003). 

40 Multiple speakers and panel discussion, “6th Annual National Forum on Biomedical 

Imaging in Oncology” NCI/NEMA (Bethesda, MD, April 7 – 8, 2005). 

41 G. Boas, “Near-IR Fluorescence Imaging Identifies Arthritis in Mice,” Biophotonics 

International, 11 #11 51-52 (November, 2004). 

42 H. Hogan, “Imaging Eyes in a New Light,” Biophotonics International 12 #1 51 – 52 

(January 2005). 

48
43 “Pioneering New Applications for OCT Research,” RLE currents (J.H. Shapiro, Editor 

in Chief) 11 #2 (Fall, 1999). 

44 W. Drexler, U. Morgner, F.X. Krtner, C. Pitris, S.A. Boppart, X.D. Li, E.P. Ippen, and 

J.G. Fujimoto, “In Vivo Ultrahigh-Resolution Optical Coherence Tomography,” Opt. 

Lett. 24 #17 1221-1223 (September, 1999). 

45 U. Morgner, W. Dexler, F.X. Krtner, X.D. Li, C. Pitris, E.P. Ippen, and J.G. Fujimoto, 

“Spectroscopic Optical Coherence Tomography,” Opt. Lett. 25 #2 111-113 (January, 

2000). 

46 I. Hartl, X.D. Li, C. Chudoba, R.K. Ghanta, T.H. Ko, J.G. Fujimoto, J.K. Ranka, and 

R.S. Windeler, “Ultrahigh-Resolution Optical Coherence Tomography Using Continuum

Generation in an Air Silica Microstructure Optical Fiber,” Opt. Lett. 26 #9 608-610 

(May, 2001). 

47 K. Leggett, “Fluorescence Analysis Used to Map Colon Cancer,” Biophotonics 

International 12 #3 (March 2005). 

48 N. Anscombe, “Light Promises Painless Diabetes Management,” Biophotonics 

International 10 #11 44-47 (December 2003). 

49 S.M. Reiss, “Laser System Helps Quantify PDT Drug Concentrations,” Biophotonics 

International, 11 #9 16-17 (September, 2004). 

50 R. Landry, FDA/CDRH, private conversation (November, 2004). 

51 N. Walker, “Evaluating the Safety of Materials Produced Through 

Nanotechnology: A Big Issue in a Small World”, Workshop on Biomedical Applications 

of Nanotechnology, NIBIB/DOE (Bethesda, MD March 2005). 

52 V. Vilker, Biotechnology Division, CSTL, private communication (May 2005). 

49
V. APPENDIX I: NIST staff sources for this report 

- Solid-State Lighting

o Clare Allocca, MSEL 

 clare.allocca@nist.gov

 301-975-4359 

o Kris Bertness, EEEL, Optoelectronics 

 bertness@boulder.nist.gov

 303-497-5069 

o Wendy Davis, PL, Optical Technology 

 wendy.davis@nist.gov

 301-975-6963 

o Marty Green, MSEL, Ceramics 

 martin.green@nist.gov

 301-975-8496 

o Debbie Kaiser, MSEL, Ceramics 

 debra.kaiser@nist.gov

 301-975-6119 

o Tom Lettieri, ATP, Information Technology and Electronics 

 thomas.lettieri@nist.gov

 301-975-3496 

o Yoshi Ohno, PL, Optical Technology 

 yoshihiro.ohno@nist.gov

 301-975-2321 

o Albert Paul, MSEL, Ceramics 

 albert.paul@nist.gov

 301-975-6004 

o Larry Robins, MSEL, Ceramics 

 lawrence.robins@nist.gov

 301-975-5263 

o Kent Rochford, EEEL, Optoelectronics 

 rochford@boulder.nist.gov

 303-497-5285 

- Photonics in Healthcare 

o Clare Allocca, MSEL 

 clare.allocca@nist.gov

 301-975-4359 

o Eric Amis, MSEL, Polymers 

 eric.amis@nist.gov

 301-975-6681 

o Marcus Cicerone, MSEL, Polymers 

 marcus.cicerone@nist.gov

 301-975-8104 

o Marla Dowell, EEEL, Optoelectronics 

 mdowell@boulder.nist.gov 

50
 303-497-7455 

o Adolphas Gaigalas, CSTL, Biotechnology 

 adolfas.gaigalas@nist.gov

 301-975-2873 

o Mrunal Chapekar, ATP, Chemistry and Life Sciences 

 mrunal.chapekar@nist.gov

 301-975-6846 

o Gradimir Georgevich, ATP, Chemistry and Life Sciences 

 gradimir.georgevich@nist.gov 

 301-975-2180 

o Lori Goldner, PL, Optical Technology 

 lori.goldner@nist.gov

 301-975-3792 

o Marty Green, MSEL, Ceramics 

 martin.green@nist.gov

 301-975-8496 

o Angie Hight Walker, NIST-NIH Liaison 

 angela.hightwalker@nist.gov 

o Jeeseseong Hwang, PL, Optical Technology 

 jeeseong.hwang@nist.gov

 301-975-4580 

o Debbie Kaiser, MSEL, Ceramics 

 debra.kaiser@nist.gov

 301-975-6119 

o Tom Lettieri, ATP, Information Technology and Electronics 

 thomas.lettieri@nist.gov

 301-975-3496 

o Steve Stranick, CSTL, Surface and Microanalysis Science 

 stephan.stranick@nist.gov

 301-975-2348 

o Vincent Vilker, CSTL, Biotechnology 

 vincent.vilker@nist.gov

 301-975-5066 

o Mike Walsh, ATP, Chemistry and Life Sciences 

 michael.walsh@nist.gov

 301-975-5455 

o Paul William, EEEL, Optoelectronics 

 pwilliam@boulder.nist.gov

 303-497-3805 

51
VI. APPENDIX II: Non-NIST sources 

- Government

o DARPA

 Mildred Donlon, Biosensor Technology 

• mdonlon@DARPA.mil

• 703-696-2289 

 Morely Stone, Defense Sciences Office 

• mstone@DARPA.mil

• 571-218-4504 

o DOE 

 James Brodrick, Building Technologies Program 

• james.brodrick@ee.doe.gov

• 202-586-1856 

 Eddie Christy, NETL 

• eddie.Christy@netl.doe.gov

• 304-285-4604 

 Paul Gottlieb, Assistant General Counsel for Technology Transfer 

& IP 

• Paul.Gottlieb@HQ.DOE.GOV

• 202-586-3439 

o FDA 

 Janusz Beer, DHHS/FDA/CDRH/OSEL/DB 

• jzb@cdrh.fda.gov

• 301-443-7159 

 Bob James, DHHS/FDA/CDRH/OSEL/DP 

• robert.james@fda.hhs.gov

• 301-827-4686 

 Bob Landry, DHHS/FDA/CDRH/OSEL/DP 

• irobert.landry@fda.hhs.gov

• 301-827-4687 

 Josh Pfefer, 

• 301-827-4679 

o NIH 

 Rohit Bhargava, NIDDK 

• 301-496-6847 

 Ira Levin, NIDDK 

• iwl@helic.nih.gov

• 301-594-3608 

 Dick Swaja, NIBIB 

• swajar@nbib.nih.gov

• 301-451-4779 

 Yantian Zhang, NIBIB 

• YZhang1@mail.nih.gov

52
• 301-402-1373 

o NSF 

 Leon Esterowitz, Division of Bioengineering & Environmental 

Systems 

• lesterow@nsf.gov

• 703-292-7942 

- Non-government 

o Organizations 

 OIDA, www.oida.org/

• Reports 

• Workshop attendance 

 NEMA, www.nema.org/

• Reports 

 Next Generation Lighting Industry Alliance, 

www.nema.org/prod/lighting/ solid/upload/NGLIA-fact-sheet.pdf

• Reports 

• Workshop attendance 

o Companies 

 Cree 

• James Ibbetson 

o james_ibbetson@cree.com

o 805-968-9460 

• Primit Parikh

o Primit_Parikh@cree.com

o 805-968-9460 

• Brend Keller 

o Bernd_keller@cree.com

o 805-968-9460 

 Kyma Technologies, Inc. 

• Drew Hanser 

o hanser@kymatech.com

o 919-789-8880 

 Nanocrystal 

• Nikhil Taskar 

o ntasker@nanocrystals.com

o 914-282-6063 

53
- Universities (Note: this information is provided as an additional resource for the 

reader. Conversations with researchers from some of the universities listed were 

held at meetings and conferences. However, unlike the contacts listed above, no 

specific effort was made to contact individual universities, since this document 

was envisioned as a mapping of future research needs as perceived by industry 

and government agencies.) 

o SSL: the following list is composed predominately of universities funded 

as part of the DOE SSL program

 Boston University

• Theodore Moustakas 

o tdm@bu.edu 

o 617-353-5431 

 Brown University 

• Arto Murmikko 

o arto_murmikko@brown.edu 

o 401-863-2869 

 Georgia Tech Research Corp. 

• Russell Dupuis

o russell.dupuis@ece.gatech.edu 

o 404-894-2688 

 Georgia Tech Research Corp. 

• Ian Ferguson 

o ianf@ece.gatech.edu 

o 404-385-2885 

 North Carolina State University 

• Mark Johnson 

o mark_johnson@ncsu.edu

o 919-513-2480 

 University of California, San Diego 

• Joanna McKittrick 

o jmckittrick@ucsd.edu 

o 885-534-0112 

 University of California, Santa Barbara 

• Shuji Nakamura 

o shuji@engineering.ucsb.edu 

o 805-893-5552 

 University of Florida

• David Norton 

o dnort@mse.ufl.edu 

o 352-846-0525 

 University of Georgia Research Foundation 

• Uwe Happek 

o uhappek@physast.uga.edu 

o 706-542-2859 

 University of Southern California 

• Mark Thompson 

54
o met@usc.edu 

o 213-740-6402 

 University of California, Santa Barbara 

• Guillermo Bazan

o bazan@chem.ucsb.edu 

o 805-893-5538 

o Photonics in Healthcare: The NSF has set up an NSF Center for 

Biophotonics Science and Technology led by the University of California 

at Davis with activities at a number of other institutions. 

Administrative contact:

 University of California, Davis – lead university 

• Dennis Matthews, Center Director 

o matthews1@llnl.gov 

o 925-422-5360 

Research contacts: 

• University of California, Berkeley 

o Jay Groves 

 jtgroves@lbl.gov

 510-643-0186 

• University of California, San Francisco 

o John Sedat 

 sedat@msq.ucsf.edu

 415-476-4156

o Mats Gustafsson 

 mats@msg.ucsf.edu

 415-514-4385 

o David Agard 

 agard@msg.ucsf.edu 

 415-476-2521 

o Shane Burch 

 burchs@orthosurg.ucsf.edu 

 415-476-8104 

• University of California, Los Angeles 

o Shimon Weiss 

 sweiss@chem.ucla.edu

 310-794-0093 

• Stanford University 

o Chris Contag 

 ccontag@stanford.edu

 650-725-8781 

o Mark Schnitzer 

 mschnitz@stanford.edu

55
 

• Alabama A&M University 

o Ravi Lal 

 rlal@aamu.edu

 256-372-8148 

o Anup Sharma 

 Anup.sharma@aamu.edu

 256-372-8102 

• University of Texas, San Antonio 

o Dhiraj Sardar 

 dhiraj.sardar@utsa.edu

 210-458-5462 

• Mills College

o Susan Spiller 

 spiller@mills.edu

 510-430-3175 

• Fisk University 

o Arnold Burger 

 aburger@fisk.edu

 615-329-8516 

• Arizona State University

o John Spence 

 spence@asu.edu

 602-965 6486 

• University of Toronto 

o Brian Wilson 

 wilson@uhnres.utoronto.ca 

 416-946-2952 

• University of Laval (Quebec) 

o Yves de Koninck 

 Yves.DeKoninck@crulrg.ulaval.ca

 418-663-5747 

• National Yang Ming University (Taiwan) 

o Arthur Chiou 

 aechiou@ym.edu.tw

• Chinese University Hong Kong 

o Chinlon Lin

 chinlon@ie.cuhk.edu.hk

 852-2609-8370 

 

- 

56
VII. APPENDIX III: ATP funded projects 

SSL: 

Status Project Number Title 

Completed 1998-02-0016 100-Millimeter Semiconductor Wafer Processing 

Technology for InP-Based Photonic Devices 

Completed 1993-01-0205 Holographic Graded-Index, Non-Lambertian 

 Scattering Screens and Components with 

 Light-Shaping Capability 

Completed 1991-01-0142 Manufacturing Technology for High Performance

 Optoelectronic Devices Based on Liquid Phase 

 Electro-Epitaxy

Completed 1991-01-0263 A Feedback-Controlled Metalorganic Chemical 

 Vapor Deposition Reactor 

Completed 1991-01-0256 Advancement of Monocrystalline Silicon Carbide 

 Growth Processes

Completed 1998-02-0058 Manufacturable Solid-State Lighting 

Active 2004-1E-7011 Low Cost, High Efficiency Chip Scale LED Lamp 

Active 2004-1E-7075 Processes for Growing Large, Single Crystal 

 Aluminum Nitride

Photonics in Healthcare: 

Status Project Number Title

Completed 1994-05-0004 Compact Blue Laser for Diagnostics

Completed 1994-05-0017 Molecular Cytogenetics Using the Genescope: An 

Ultrafast Multicolor System for Automated FISH 

Analysis 

Completed 1994-05-0018 SBH Format 3 Megabase Diagnostics 

Instrumentation 

Completed 1994-05-0030 Diagnostic Laser Desorption Mass Spectrometry 

Detection of Multiplex Electrophore Tagged DNA 

Completed 1995-08-0012 Development of Bar Code Diagnostics for DNA 

Diagnostics 

Completed 1995-08-0023 Arrayed Primer Extension (APEX): The Next 

Generation DNA Analysis System for Sequencing 

in DNA Diagnosis 

Completed 1997-07-0001 Combinatorial Cell Culture: Tool Development and 

Application to Human Stem Cell Growth 

Completed 1998-01-0154 Non-invasive Glucose Measurement Using 

Chemical Amplification and Optical Sensing 

Completed 1998-01-0163 Development of Next-Generation OCT Technology 

Completed 1998-08-0020 Multiplex DNA Diagnostic Assay Based on 

Microtransponders 

57
Active 2000-1A-4106 Blood "Fingerprinting": A First Step Toward 

Personalized Medicine 

Completed 2000-1B-4140 A Novel Intraoral Three Dimensional Digitizer for 

Digital Dentistry 

Active 2001-1E-4406 Long-Term Implantable Optical Blood Glucose 

Monitor 

Active 2002-3B-5694 Microsphere-Based Spectroscopic Instruments 

Active 2004-1B-7002 Quantum Dots for Biomedical and Consumer 

Applications 

 

58
VIII. APPENDIX IV: Benefits accrued to ATP detail

Benefits accrued to this ATP detail fall into three interrelated categories: benefits to the 

ATP, benefits to the NIST Laboratory, and benefits associated with personal 

development. 

- Benefits to ATP include transfer to the Electronics and Photonics Group technical 

knowledge of materials science issues related to electronics and photonics 

applications, participation on the Electronics and Photonics Board during 

competition, extension of the ATP reviewer pool, and increased contact with 

other government agencies. In addition, the current state of the art in two 

emerging photonics areas, Solid State Lighting and Healthcare, has been analyzed 

and the information has been organized and disseminated to the ATP in both 

verbal and written form, along with listings of internal NIST and external 

government, industry, and university contacts. Finally, the detail has advanced 

interactions between the ATP and NIST Laboratories through both formal and 

informal interactions. 

- Benefits to the Laboratories mirror those to the ATP to a large extent. 

Relationships that have been developed with other government agencies are 

potentially very valuable. Similarly, the information obtained on the two 

technical areas described in this document provides the Laboratories an 

opportunity to evaluate two emerging areas, including scientific and technical 

barriers, customers, economic importance, and sources of potential collaborators. 

While the benefits described heretofore were anticipated, benefits resulting from

informal interactions between ATP staff and laboratory staff were more 

serendipitous but equally important. An example of such an interaction is the 

informal meeting between two Ceramics Division staff and two ATP staff at 

which generic issues associated with biomarkers were discussed. The discussion 

helped lead to a formal interaction between the Ceramics Division and NIH 

investigating nanoscale particle analysis. 

- Benefits of combining NIST laboratory and ATP experience include the 

opportunity to work closely with groups of people with widely varying 

backgrounds. The opportunity to make contacts with people in other government 

agencies is potentially very valuable for the development future research projects. 

With respect to the areas of Solid State Lighting and Photonics in Healthcare, the 

knowledge gained in developing this report will, inevitably, remain much greater 

than the knowledge transmitted to the ATP or the Laboratories via formal written 

or oral presentations. However, even the knowledge not transmitted formally will 

find its way into future research projects as they evolve and, therefore, will 

remain very valuable. Finally, observation of the mechanisms by which the ATP 

operates, mission driven and criteria directed with a clear vision for technology 

transfer into the economy, has helped formulate a formalized evaluation 

procedure that can be used to assess future research choices in the NIST 

laboratories. 

59