Table of Contents 

Table of Contents................................................................................................................ 1

Preface................................................................................................................................. 2

Regulatory Support Activities............................................................................................. 5

Office of Science and Engineering Laboratories 2011 Highlights..................................... 7

Division Descriptions........................................................................................................ 23

Office of Science and Engineering Laboratories.............................................................. 29

Research Laboratories and Selected 2011 Accomplishments .......................................... 29

APPENDIX A – OSEL Publications................................................................................ 50

APPENDIX B – OSEL Presentations............................................................................... 58

Breger J, Fisher B, Isayeva I, Baeva L, Wang N. Optimization of the 'click' reaction for 

therapeutic cell encapsulation utilizing RIN-5F cells. Biomedical Engineering Society 

2011 Annual Meeting, Hartford, CT, October 12-15, 2011. ............................................ 60

Hitchins V. FDA’s perspective of “clean” for reprocessing medical devices. Association 

for the Advancement of Medical Instrumentation and FDA, AAMI/FDA Medical Device 

Reprocessing Summit, October 12, 2011. ........................................................................ 60

Choi J, Reipa V, Hitchins V, Goering P, Malinauskas R. Human blood biocompatibility 

of silver nanoparticles. AIChE (American Institute of Chemical Engineers), Annual 

Meeting of Chemical Engineers, October 16, 2011.......................................................... 60

Brown R. The basic elements of biocompatibility studies. FDA, Basic Nonclinical 

Bioresearch Monitoring, October 17, 2011. ..................................................................... 60

Elespuru RK, Rajani A. Evolution of colon cancer is reflected in DNA mutational 

sequence profiles. Environmental Mutagen Society 42nd Annual Meeting, Montreal, 

Canada, October 15-19, 2011. Elespuru RK, Rajani A. Miniaturization of a Salmonella 

Typhimurium genotoxicity assay. Environmental Mutagen Society 42nd Annual Meeting, 

Montreal, Canada, October 15-19, 2011. Fisher B. (Developmental) toxicity testing in 

the 21st century: Leveraging for alternative models. Middle Atlantic Reproductive and 

Teragology Association (MARTA), 2011 MARTA Meeting, October 20, 2011. ........... 60

Brown R. Biological effects of cobalt and chromium released from CoCr alloy: Research 

activities in the CDRH/OSEL Laboratory of Toxicology and Biocompatibility, National 

Institute of Standards and Technology, Failure of Metal-on-Metal Hip Implants Meeting, 

November 17, 2011........................................................................................................... 61

Wood S. Development of anti-Ebola MHC tetramers as a surrogate marker to evaluate 

cell-mediated immunity in vaccines:a computational approach, NIAID Research update, 

November 21, 2011........................................................................................................... 61

APPENDIX C – OSEL Academic Affiliations ................................................................ 70

APPENDIX D – OSEL Science Sharing Seminars.......................................................... 74

APPENDIX E – Laboratory Leaders................................................................................ 77

APPENDIX F – OSEL Organization Chart...................................................................... 79
2

Preface 

The Office of Science and Engineering Laboratories (OSEL), one of seven Offices within 

CDRH, contributes to the Center’s mission by providing laboratory data and consults. 

OSEL serves as the laboratory science nucleus for the Center. Specifically, OSEL helps 

provide a scientific foundation for the Agency’s regulatory decision- making by 

developing independent laboratory information for regulatory and other public health 

activities of CDRH. In addition to providing consultation to the Center’s regulatory 

experts, OSEL researchers are involved in mission-oriented science activities including 

test methods development, risk assessments, forensic investigations, product evaluations, 

and technology assessment.

The research in OSEL is broad and cross-cutting, with research conducted in the 

physical, life, and engineering sciences as related to the effects of medical devices on 

human health. CDRH relies upon this work to support its efforts ensuring public safety in 

areas as varied as medical imaging, medical device software, breast implants, and drug 

eluting stents. 

OSEL laboratory science provides an important foundation for the regulatory mission of 

the Center and the Agency and in implementing the primary directive to protect the 

public health. Among the many accomplishments of OSEL:

1. The scientific research conducted in OSEL laboratories is significant, with great 

public health impact. One such example is the Huber needle investigation. Huber 

needles are used to access ports that are implanted under the skin of chronically ill 

patients for continued access to the veins for blood withdrawal and for delivering 

medication, nutritional solutions, blood products, and imaging solutions. These 

needles should be designed to penetrate the port without cutting and dislodging 

any silicone cores (or slivers) from the ports into which they are inserted.

When FDA received reports of leakage after accessing a port with a Huber needle 

(labeled to be non-coring), OSEL scientists assisted the Agency by conducting

laboratory testing of Huber needles from multiple manufacturers. The testing 

showed that certain Huber needles produced cores when inserted into ports.

2. OSEL created a new laboratory, the Functional Performance and Device Use 

Laboratory, to assess the needs of medical device users in varied-use 

environments, using multiple-device user interfaces to expand understanding of

how medical device design influences use errors and physical performance. The 

creation of this laboratory was in response to the adverse events data showing that 
3

as many as one-third of medical device failures causing patient harm and reported 

to the FDA appear to be failures of medical device use rather than failure of the 

device itself. One priority discussed in the CDRH 2011 report, “A Vital 

Framework for Protecting and Promoting Public Health,” was improving 

medical device safety. A key approach to this laboratory’s research would be “to 

help reduce use error, enhance patient and user safety, improve product usability 

and efficiency, and enhance user satisfaction with medical devices.” 

3. All Centers in FDA continue to receive products containing nanotechnology and 

nanomaterials. The FDA Nanotechnology Taskforce recognized that 

characterization of nanomaterials is a key component of FDA research; and there 

is a need to establish a core laboratory facility accessible to all of the Centers, and 

whose primary function is to provide specialized equipment and tools that are 

basic to all nanomaterial-related research projects. The Core facility was 

established in OSEL/CDRH in 2011 with the purchase of three pieces of 

equipment:

OSEL continues its outreach to the scientists and engineers of tomorrow. Since first 

begun in 2003, the OSEL student science poster exhibit has become a much-anticipated

annual event. What began as an in-house event to provide a forum for young future 

scientists in OSEL to discuss their work with one another has now become a symposium 

for collaboration among interns from other FDA components, federal agencies, and

various academic institutions—both at the high-school, and college and university levels.

The annual exhibit continues to expand and draw interest from non-FDA science and 

health-care professionals.

The OSEL Annual Report offers timely information about the Office’s organization and 

intramural science activities; provides a summary of the Office’s direct laboratory 

support for pre-market review and post-market evaluation; and provides a bibliography of 

scientific publications, presentations, and research seminars for the fiscal year reported. 

The information is within the framework of OSEL’s organization structure: divisions are 

first described, followed by descriptions of the research laboratories. The section on 2011 

highlights lists examples of specific successful OSEL research projects and laboratory 

accomplishments. This report also cites a few examples of the regulatory support work 

that OSEL provides to the Center’s post-and pre-market offices. 

We hope you find this document useful and informative. We welcome your comments on 

the programs described in this report. 

For additional information, please visit the OSEL web site at 

http://www.fda.gov/cdrh/osel or contact us at 301-796-2530.

 
4

Steven K. Pollack, Ph.D.

Director

Office of Science and Engineering Laboratories 

Center for Devices and Radiological Health, FDA

Disclaimer: Please note that the mention of commercial products, their sources, or their 

use in connection with material reported herein is not to be construed as either an actual 

or implied endorsement of such products by the Department of Health and Human 

Services.
5

Regulatory Support Activities 

Research conducted in the OSEL supports the regulatory activities of the Agency as 

follows: 

· Strategically manage research with the aim of providing a scientifically sound 

basis for responding to current needs and anticipating future regulatory 

challenges; and

· Provide technical consults in support of the Center’s pre-market, post-market, and 

compliance activities. 

Both activities are coordinated within OSEL in an effective manner so as to best meet 

Center’s regulatory science needs. Laboratory research is the cornerstone upon which the 

Office provides the regulatory support function. (The research is described in subsequent 

sections.) It is largely based on investigations related to the mechanistic understanding of 

device performance or test procedures, enabling the Center and device manufacturers to 

gain an improved understanding of issues related to safety and efficacy. In general, 

although the research is directed toward issues identified at the pre-market approval 

level, the reality is that the research has the largest impact on the post-market end of the 

Center’s business because most often the research is anticipatory in terms of potential 

issues of medical devices identified at the pre-market level. 

The regulatory support function of the Office is provided through consults supporting 

both pre-market decisions and post-market actions using expertise developed in the 

laboratory. A consult is a request for expert advice or information of a specific nature, 

and provides information that contribute to sound regulatory decisions. Consults are often 

based on acknowledged scientific/engineering principles or on independent data 

generated in OSEL laboratories. 

In 2011 OSEL provided the following:

Number of consults on pre-market issues 1780

Number of consults on post-market issues 142

The information provided by a consult is used in some of the following ways:

· Evaluate a pre-market submission (IDE, HDE, PMA, 510(k)); 

· Support a compliance action (regulatory case support/development, Health 

Hazard Evaluation, Health Risk Assessments, etc.); 

· Assist scientific collaboration; 
6

· Respond to a consumer inquiry; 

· Provide feedback on guidance documents; 

· Provide revisions to one-pagers for the new device approval page; 

· Support health hazard evaluation/health risk assessments in device 

determinations/classifications. 

For many post-market as well as pre-market regulatory issues, the consults/reviews and 

investigations conducted by OSEL independently assess the claims made by 

manufacturers or other parties concerning safety or effectiveness. In other cases, OSEL 

reviews may assess the adequacy of a design, a failure investigation, a production 

process, or a quality process employed by the manufacturer. These reviews and analyses 

rely on in-house expertise and are often augmented by expertise solicited from colleagues 

in academia, other government laboratories, or even other industry sectors. OSEL 

laboratory investigations may be undertaken in instances where the veracity of a 

performance claim needs to be independently verified by testing or when the claimant 

lacks the resources to conduct the investigation. 

OSEL also provides analytical support to post-market regulatory activities in a variety of 

ways: 

· Provide scientific and engineering reviews and analyses; 

· Conduct laboratory investigations of product performance;

· Participate in inspections of medical device establishments;

· Conduct forensic reviews and investigations; 

· Identify device safety and performance issues; 

· Provide training to FDA and industry; and 

· Contribute to Center-wide Matrix teams on issues identification as well as 

science-based analysis of post-market device performance. 

Finally, developing standards and measurements methods is a significant activity of this 

office. OSEL continues to provide innovative solutions to public health problems by 

constructing generic techniques that lead to the creation of national and international 

standards that will enhance product safety and effectiveness. OSEL staff actively

participate in developing standards at the national and international levels by performing 

research to establish standard procedures, and by shouldering standards committees 

responsibilities to manage, develop and support standards development. 
7

Office of Science and Engineering Laboratories 2011

Highlights

Development of a Nanoparticle-based Phantom for Assessment of Retinal OCT Device 

Performance (Optical Diagnostic Devices Laboratory, Division of Physics)

Optical coherence tomography (OCT) is an FDA-cleared imaging modality now being 

used 16 million times annually to image the eye with devices from at least 6 different 

manufacturers. Although OCT is extensively used, there are no standardized test methods 

that ensure the accuracy and consistency of OCT data. Controlled test objects known as 

phantoms can fill this gap by serving as a stable, well-characterized reference, which is 

imaged for preclinical assessment as well as periodically during clinical use for quality 

assurance. Optical Diagnostic Devices Laboratory (ODDL) researchers have recently 

designed, fabricated and validated a novel nanoparticle-based phantom specifically for 

benchmarking the performance of retinal OCT devices. The phantom comprises a 

precisely shaped transparent polymer with embedded gold nanoshells placed at the retinal 

plane of a model eye that realistically replicates the focusing characteristics of the human 

eye. The nanoparticles reflect light from the OCT scanner beam, enabling accurate 

measurement of the device's point spread function. This provides a detailed 

representation of the device’s spatial resolution and its variation throughout the imaging 

volume. The phantom, which is easy to use and portable, has been evaluated on a 

research-grade retinal OCT device in ODDL. The fabrication methods and evaluation 

results form the basis of a manuscript that has recently been submitted for publication in 

a scientific journal. Through its research on novel, phantom-based test methods for 

optical imaging, ODDL is facilitating science-based evaluation and regulatory clearance 

of innovative, minimally invasive devices with the potential to impact public health. 

Brain Computer Interfaces (Biophysics Laboratory, Division of Physics)

Dr. Cristin Welle and staff of the Biophysics laboratory developed a platform to assess 

physiological, anatomical, chemical and behavioral responses to invasive recording 

electrodes in the brain. This is an important development because of the need to improve 

and assure the long-term safety and reliability of these novel implants. Neural implants 

have the potential to provide an unparalleled capability for individuals using prosthetic 

devices to interact with their external environment. Currently, these devices have fallen 

short of their potential due to a longitudinal decline in their ability to detect neural 

signals. This failure may result from biological reactions that result from inserting a 

foreign object into the brain, or from gradual decay of the electrode materials, although 
8

the precise failure mechanisms have yet to be determined. The Division of Physics 

entered into a collaborative research endeavor with DARPA’s (Defense Advanced 

Research Projects Agency) Reliable Neural Interface Technology (RE-NET) program 

based on a common interest in the long-term safety and reliability of neural implants. Dr. 

Welle’s expertise in cortical electrophysiology, two-photon imaging and small animal 

survival surgery has been leveraged to develop innovative test platforms to identify 

biomarkers predictive of long-term implant success. The DP platform to identify 

physiological markers that are predictive of failure will see several types of neural 

electrodes implanted in a genomically controlled mouse model. Single-unit and local 

field potential electrophysiological data will be recorded weekly for 12 months. 

Additionally, in-vivo two-photon imaging on a weekly basis from individual animals will 

observe neural death and morphological changes, and automatic computerized detection 

of freely moving behaviors will be correlated with the electrophysiology to link features 

important to motor control. In parallel, DP researchers will perform accelerated aging 

protocols in an artificial brain to assess chronic electrode integrity and function through 

electrochemical analysis. These investigations identify the factors that are critical to 

electrode longevity and establish test platforms that can be used to aid the regulatory 

decisions regarding penetrating neural interfaces. 

CDRH-Transportation Security Laboratory Interagency Project on Electromagnetic 

compatibility (EMC) (Electromagnetic and Wireless Technologies Laboratory, 

Division of Physics)

The Transportation Security Laboratory (TSL), Department of Homeland Security (DHS) 

sought the expertise of OSEL’s Division of Physics to assess the potential 

electromagnetic interference (EMI) risks for airline passengers with personal electronic 

medical devices (PMEDs) screened with new advanced imaging technology (AIT) 

systems. This project is being performed under an interagency agreement between FDA 

and TSL/DHS. It follows previous interagency agreements with TSL in such areas as the 

study of the potential effects on personal medical devices (PMEDs) from exposure to 

magnetic fields from metal detector security systems. The present project involves testing 

and research centered on the potential effects on PMEDs from exposure to the emissions 

from new millimeter wave body scanner systems. This technology operates by emitting 

very low levels of electromagnetic fields at very high frequencies (millimeter waves) to 

create an image of the subject to search for contraband. Because of the dearth of 

information about medical device exposures to such high-frequency emissions, the OSEL 

laboratory research project developed novel methods to test and assess effects on 

PMEDs. The PMEDS included implantable cardiac pacemakers and implantable 

cardioverter defibrillators, implantable neurostimulators, and drug infusion pumps such 

as body-worn insulin pumps. The test methods were adapted from earlier OSEL studies 

involving use of a simulated human body torso. A new simulated torso had to be made 
9

for the present study because of the nature of the millimeter wave fields, since they can 

be more highly attenuated in the body than fields at lower frequencies. 

To assess the exposures, measurements were made of the emissions at several locations 

in and around the millimeter wave AIT system. These measurements help in developing a 

unique system to simulate the emissions from the AIT that was used to develop a simple 

and more easily implemented way to reproduce the AIT exposure. Using the novel testing 

methods and materials, testing was performed over a range of different makes and models 

of the implantable and body-worn PMEDs at various positions and orientations in and 

around the AIT unit. The programming and functioning of each PMED was carefully 

monitored during these tests. Findings indicated no effects on the functioning of any 

PMEDs at any of the locations or orientations. The risks for effects on the PMEDs studies 

for this AIT were assessed to be very low. In addition to the PMED study, the emissions 

measurements were assessed for radiation safety in reference to the American National 

Standards Institute (ANSI) Institute for Electrical and Electronics Engineering (IEEE) 

C95.1 Standard for human exposure to non-ionizing electromagnetic radiation. The 

emissions measurements revealed very low exposures for the person being scanned or 

nearby security personnel. Exposures were found to be at least 1000 times below the 

limits of the human exposure standards. 

Comparative Study of Temperature Measurements in Ex-vivo Swine Muscle and a TissueMimicking Material during High Intensity Focused Ultrasound Exposures (Ultrasonics 

Laboratory, Division of Solid and Fluid Mechanics)

High-intensity focused ultrasound (HIFU) is a leading-edge, minimally invasive 

technology for surgery without incisions. Dozens of active development efforts are 

underway around the globe for applications such as ablating pathologic tissue and 

stopping internal bleeding. As with many emerging technologies, HIFU has a need for 

reliable standardized test methods. Existing test methods have been complicated, poorly 

characterized, and often unreliable. To enable meaningful testing by sponsors and 

developers, Ultrasonics Laboratory scientists within the Division of Solid and Fluid 

Mechanics have developed tissue-mimicking materials (TMMs) for characterizing new 

HIFU products. When TMMs containing thermal sensors are used to measure ultrasoundinduced temperature rise, it is important that measurement results reasonably represent 

those that occur in biological tissue. Therefore, the thermal behavior of the TMM under 

HIFU exposure was compared to that of ex vivo tissue (freshly excised swine muscle). 

Temperature traces obtained at various pressure levels demonstrated similar types of 

heating profiles in both the tissue and TMM, the exact nature of which depended on 

whether bubbles formed during the HIFU exposure. Knowledge gained from this research 

will facilitate the evaluation of preclinical data submitted by device sponsors, and will aid 

in developing bench testing guidance and standards. A peer-review paper describing the 

methodology and results was published recently in Physics in Medicine and Biology.
10

Contact Lens Contamination Project (Division of Chemistry and Materials Science)

In 2006-2007, a series of widespread Fusarium and Acanthamoeba outbreaks threatened 

contact lens users in the United States and abroad, making public health authorities 

increasingly aware of the need for better pre-market testing methods to evaluate contact 

lens product safety. Experts advised that a single grouping for silicon hydrogels was not 

adequate to predict potentially harmful lens-solution interactions. Scientists in the 

Division of Chemistry and Materials Science were charged with performing scientific 

testing of various physical properties of conventional and silicon hydrogel lenses to 

determine how they could be grouped to safely predict solution interactions. DCMS staff 

worked with staff within the Office of Device Evaluation (ODE) to devise a laboratory 

research strategy that would target some of the most important properties of polymer 

materials that affect material-solution interactions. This served to familiarize them with 

both DCMS research capabilities and proposals of analytical methods to answer key 

questions. The team mapped their strategy based on the hypothesis that silicon hydrogels 

could be grouped with most of the same properties (water content and charge) as 

conventional hydrogels, with the exception of one property (hydrophobicity). 

The work done by DCMS involved five different research areas: water states, pore sizes, 

hydrophobicity, and protein and lipid uptake. In each of these areas, DCMS staff used 

their extensive research experience and scientific knowledge to devise experimental 

strategies to answer the questions that the team had about silicon contact lens properties 

and interactions. DCMS researchers also relied heavily on a number of advanced 

instruments available in OSEL for research, including microscopy, thermogravimetric 

tools and wet laboratory resources. When combined with results from additional studies 

being done by staff in the Division of Biology, the results of these experiments allowed 

the team to devise an improved grouping strategy to help predict interaction of current 

and future care product components with wide-ranging contact lens materials. ODE will 

be proposing the new grouping strategy to the contact lens industry and other regulatory 

bodies as a new standard grouping system that can be used to predict potential harmful 

lens-solution interactions. The use of this grouping system will greatly simplify lens 

testing for manufacturers; and as more and more silicon hydrogel lenses and lens care 

products come to market, it will help ensure consumer safety by preventing harmful lenssolution combinations. Labeling changes can also be made to warn about specific care 

product interactions where depletion of preservative might allow microbial 

contamination, or otherwise harmful interactions might occur. The work has not only 

resulted in several submitted scientific publications and an invited presentation to the 

Contact Lens Association for Ophthalmology (CLAO) conference, but it is also being 

used at FDA to help develop improved guidance and standards documents for contact 

lenses and care products. 
11

Fig. 1 Image of fluorescent probe penetration in a contact lens obtained using confocal laser scanning microscopy 

(CLSM) 

Fig. 2 LCDR Kenneth Phillips, PhD and Allan Guan, B.S. using the Tecan Infinite M1000 microplate reader to 

measure biomolecular contamination on contact lens materials 

Creation of the Functional Performance and Device Use Laboratory (Functional 

Performance and Device Use Laboratory, (Division of Physics)

As many as one-third of medical device failures causing patient harm reported to the 

FDA appear to be failures of medical device use rather than failure of the device itself. In 

2011, CDRH released the report Regulatory Science in FDA’s Center for Devices and 

Radiological Health: A Vital Framework for Protecting and Promoting Public Health,

which highlighted recent progress in regulatory science. One priority discussed in the 

report was improving medical device safety, and the newly created Functional 
12

Performance and Device Use Laboratory in OSEL’s Division of Physics was cited as a 

key approach to “help reduce use error, enhance patient and user safety, improve product 

usability and efficiency, and enhance user satisfaction with medical devices.” 

Creating this new laboratory included identifying the physical space and purchasing 

essential equipment to build broad scientific capabilities that include: 

· an extensive toolbox of hardware and software that will allow the creation of 

mock-up device user interfaces that can be modified to understand which features 

increase or decrease the probability of use-related errors; 

· an advanced motion-capture system including eye gaze tracking to allow 

quantitative analysis of how users make and respond to use-related errors; and

· a mobile laboratory to permit usability analyses of medical devices by diverse 

users in varied-use environments. 

The Functional Performance and Device Use Laboratory is now ready to assess the needs 

of medical device users in varied-use environments, using multiple device user interfaces 

to expand understanding of how medical device design influences use errors and physical 

performance. 

Development of Novel Test Methods for Evaluation of Safety and Performance Quality of 

Optical Therapeutic Techniques and Devices (Optical Therapeutics and Medical 

Nanophotonics Laboratory, Division of Physics)

To support the Center's regulatory product safety activity, the OSEL/Division of Physics’ 

Optical Therapeutics and Medical Nanophotonics (OTMN) Laboratory maintains the 

facilities and resources for developing independent test methods for preclinical testing 

and evaluating the fundamental characteristics, performance quality, and safety of new 

medical therapeutic devices that employ the latest minimally invasive medical laser and 

optical technology. In CY 2011, researchers developed alternative test methods for 

evaluating the safety and efficacy of optical therapeutic techniques and devices in the 

areas of ophthalmology and ultrashort femtosecond laser therapeutics. They have 

successfully demonstrated the advanced features of the following test methods:

(1) Two novel standard test methods for intraocular lens (IOL) implant 

characterization. Researchers developed test methods for preclinical evaluation of 

fundamental optical properties of IOL implants such as dioptric power and light 

scattering characteristics. The first method is based on an innovative optical 

coherence tomography (OCT) sensor approach for testing the dioptric power of IOL 

implants by precisely measuring IOL surface profiles and surface radii. The IOL 

dioptric power is a key parameter whose precise preclinical measurement is a part 

of the review process for all IOLs and is important to the effectiveness of IOLs. The 

proposed test method combines the advanced properties of both high-resolution 
13

OCT imaging and flexible in-situ compatible fiber-optic sensing approaches. Thus, 

the method ensures noncontact, accurate, and objective measurements of IOL 

optical power under in-situ conditions. It should provide CDRH and the device 

community with an alternative tool to evaluate IOL parameters with more precision, 

accuracy, and speed, thereby enhancing the safety and effectiveness of IOL 

implants. 

The second test method was developed for characterizing quantitatively light 

scattering effects in IOLs, which are caused by the existence of optical glistenings. 

The problem of light scattering glistenings in IOLs is of significant concern because 

it directly affects the optical quality of a patient’s vision with IOLs. Currently 

utilized test methods have not been adequate to examine light scattering from IOLs. 

The proposed test method is based on a newly established sensing approach using a 

ballistic-photon removing integrating-sphere method (BRIM). BRIM increases the 

test method's sensitivity. It provides a quantitatively simple and effective in vitro

laboratory method for accurate and objective characterization and grading of 

glistenings in various IOL of different design and/or material, regardless of their 

dioptric powers. Furthermore, this innovative technique may be exploited in more 

general applications for measuring light scattering in various biological and 

nonbiological media.

(2) Test methods for multifunctional investigation of femtosecond laser (FSL)-

tissue interactions and evaluation of safety and efficacy of FSL based 

technologies and devices. The development of novel FSL technologies and 

medical devices is an emerging field with significant public health impact in a 

variety of biomedical areas ranging from precise single-cell and robotic tissue 

surgeries to nanobiophotonics. An example of recently developed FSL-based 

technology is the application in cataract/lens replacement surgery that is the most 

commonly performed surgical procedure in the world. Some of these new 

technologies, however, have exhibited specific safety and efficacy-related concerns, 

which require independent test methods for safety and efficacy evaluation. 

Researchers have established a state-of-the-art FSL-based system that is used for 

developing multifunctional test methods used to evaluate critical characteristics of 

both FSL systems and tissues involved in the FSL-tissue interactions. The test 

methods provide monitoring and quantification of the dynamic behavior of 

fundamental FSL parameters such as wavelength, intensity, polarization, pulse 

dispersion and spatial beam characteristics, and the optical tissue properties 

including its absorption and scattering characteristics. These methods ensure an 

independent source of data for a better understanding of how FSL radiation 

propagates through and affects tissue in clinically relevant procedures. This will 

allow for safer and more efficient application of FSL therapies that should result in 

fewer complications and negative results. 
14

Development of a Standard for Validation of Computer Modeling of Electromagnetically 

Induced Heating of Human Tissues (Electromagnetic and Wireless Technologies 

Laboratory, Division of Physics)

CDRH is faced with a rapidly increasing number of pre-market applications using 

computational methods for safety and efficacy assessments. Usually sponsors employ 

commercially available software platforms, and they rely on their accuracy and validity. 

However, many software platforms lack robust code validation, and much computational 

data lacks validation of the actual computation itself. The Division of Physics (DP) in 

OSEL is working with IEEE (The Institute of Electrical and Electronics Engineers) and 

IEC (International Electrotechnical Committee) to improve this situation. FDA’s Dr. 

Wolfgang Kainz (of OSEL’s Division of Physics), Chairman of Technical Committee 34 

of the IEEE’s International Committee on Electromagnetic Safety, and his committee 

developed a document to standardize validation procedures for computational codes 

using the Finite Difference Time Domain (FDTD) Method. The document P62704-1 is 

titled, “General Requirements for using the Finite Difference Time Domain (FDTD) 

Method for SAR Calculations.” This method applies specifically to the calculation of 

induced heating from electromagnetic fields, but can also be used generally for validating 

any code using the FDTD method. It can be applied to MRI and other devices designed to 

induce, intentionally or unintentionally, tissue heating. Importantly, it specifies detailed 

validation procedures for code and the computation itself. A breakthrough was achieved 

in 2011 when the IEEE Standards Board approved this document as a dual logo 

IEEE/IEC Standard. This new dual logo status makes it possible to recognize the 

document as a CENELEC standard. CENELEC is the European Committee for 

Electrotechnical Standardization and is officially recognized by the European 

Commission as the competent European Standards Organization. Many CENELEC 

Standards are incorporated in EU Directives and are therefore mandatory. With this 

initiative, OSEL/DP expands its visibility in the United States and Europe by contributing 

internationally to standards that improve the safety and efficacy of medical devices.

First Approval of a Digital Breast Tomosynthesis (DBT) Imaging Device (Medical 

Imaging Laboratory, Division of Imaging and Applied Mathematics)

While the past decades have witnessed substantial innovation in breast imaging, screenfilm and digital mammography are still found to miss approximately 30% of breast 

cancers. These misses are often ascribed to the 2D nature of this imaging technique, in 

that the images fail to disclose cancers masked by superimposed fibroglandular tissue. 

For this reason 3D breast imaging techniques are being developed. One such technology 

is digital breast tomosynthesis (DBT), a 3D imaging technique that involves the 

acquisition of multiple lower-dose images (or projections) of the breast at different 

angles.
15

Evaluating DBT has been a substantial challenge for the Agency. In particular, 

nonclinical assessment techniques are just starting to be developed; and clinical studies 

that may be used to support effectiveness claims are complicated by a low prevalence of 

cancer in the intended population, differences between screening and diagnostic 

mammography uses, and most of all, inter- and intra-observer variability when 

interpreting the 2D and 3D images. All of these factors conspire to make evaluating DBT 

extremely challenging.

OSEL/DIAM research and expertise related to the conduct and evaluation of non-clinical 

data and imaging reader studies was directly relevant to CDRH’s review of the first DBT 

PMA submission. Based on this research and knowledge, CDRH was able to 

quantitatively demonstrate that the sponsor had selected appropriate endpoints, describe

how the data from multiple studies could be understood together, and determine what 

would be expected of the device performance when released for clinical use, given the 

limitations of the pre-market study design. Taken together, these analyses 

overwhelmingly made the case that DBT in combination with digital mammography 

significantly improved radiologist performance for breast cancer detection compared to 

digital mammography alone. The Radiological Devices panel unanimously concluded 

that the data and information submitted by Hologic supported the safety and effectiveness 

of this new technology and the Hologic DBT device was officially approved for 

marketing in February 2011. OSEL/DIAM researchers provided scientific support 

regarding the approval of this particular device, but laid forward a clear and manageable

regulatory pathway for other DBT and 3D breast imaging devices under development by 

other manufacturers.

Hermeticity Project (Materials Performance Laboratory, Division of Chemistry and 

Materials Science)

Parylene coatings are commonly used in a number of medical device applications due to 

their robust properties and ease of application. Parylene is a protective polymer coating 

material used to uniformly protect any component configuration on such diverse 

substrates as paper, glass, plastic, resin, and metal, to name a few. Recently, parylene 

(and engineered parylene derivatives) have been used in new medical devices, where an 

accurate assessment and understanding of liquid transport and its relationship to the 

polymer structure is critical in design and evaluation (for example, moisture barrier 

coatings for implantable electronics). Traditional methodologies for assessing the longterm hermeticity, and consequently the reliability, of these devices are not applicable, so 

researchers in DCMS sought out collaborations with faculty at the University of 

Pennsylvania and Drexel University to develop tools and methodologies to evaluate 

structure-performance-reliability of these coated devices. Using a combination of 

analytical techniques, they were able to determine the effects of processing on the 

parylene coating structure, which subsequently affects its barrier properties. If 
16

manufacturers are made aware of this, they may be able to adjust their processing in order 

to maximize the hermetic seal of PPX, for device reliability, thereby reducing implant 

failures and need for explant or revision surgeries.

In 2011, DCMS hosted Professor Yossef A. Elabd of Drexel University, who is a leading 

expert in the area of transport phenomena in polymers, and doctoral candidate Eric Davis 

under the Scholar in Residence Program. During his time working in OSEL, Professor

Elabd had the opportunity to collaborate and exchange ideas with several DCMS 

scientists. He also taught a Staff College course titled “Transport phenomena in 

Polymers”. These exchanges noted several areas of scientific overlap and applicability, 

and the discussions which ensued will provide critical knowledge to a number of 

regulatory issues in the medical device area. Projects that have been initiated include 

research on drug delivery through complex and biodegradable media and investigating 

the extraction of low molecular weight toxins/colorants from polymers, all of which can 

be better understood from the fundamentals of transport phenomena in polymers. 

Additionally, expertise in novel experimental approaches (such as Time-resolved Fourier 

transform infrared-attenuated total reflectance (FTIR-ATR) spectroscopy and quartz 

spring microbalance (QSM)) were exchanged. Laboratory facilities, and analysis methods 

have been developed collaboratively between Professor Elabd, Eric Davis, and DCMS 

staff. 

Fig. 3 2D wide-angle X-ray scattering patterns collected from Parylene C before and after exposure to temperature. 

These data suggest that strict control over manufacturing and post processing of these materials is critical to 

maintaining the desired properties and performance in devices.
17

Caption: Dr. Nicholas M. Benetatos preparing specimens for in-situ X-ray scattering 

experiments. 

Fig. 4 Dr. Nicholas M. Benetatos preparing specimens for in-situ X-ray scattering experiments 
18

Hydrogel Project (MATERIALS PEFORMANCE, Division of Chemistry and 

Materials Science)

Hydrogels are crosslinked hydrophilic polymer structures that are used in many 

biomedical applications including adhesion barriers, surgical sealants, soft tissue fillers, 

drug carriers, ophthalmic visco-surgical devices, etc. Hyaluronan (HA or hyaluronic acid) 

is a hydrogel material present in identical form in most tissues in animals and humans. It 

has high viscoelasticity and rheological properties. Molecules of HA can absorb a large 

volume of water, expand in the extra cellular space ,and then hydrate and lubricate tissues 

and joints. Natural HA exists as a high molecular mass polymer and can be degraded, 

absorbed and cleared by catabolic metabolism following enzymatic (hyaluronidase) 

degradation. Due to its biocompatible properties, HA has been used in a

number of biological and medical applications including soft tissue fillers, drug carriers, 

ophthalmic visco-surgical devices and adhesion barriers. 

In 2003, FDA became aware of a post-market issue regarding Gynecare Intergel ionized 

ferric hyaluronic acid (Intergel FeHA) adhesion prevention solution in which there 

appeared to be a higher frequency of adverse effects (e.g., foreign body reactions and/or 

non-infectious peritonitis) associated with this device. To address the issue, FDA 

conducted a coordinated assessment of information obtained through the adverse events 

report database associated with this device, including adverse effects associated with offlabel use in laparoscopy and non-conservative procedures such as hysterectomy.

DCMS staff used a chemistry and material science perspective to search for factors that 

might contribute to the increased risk of adverse effects following Intergel deployment in 

some patients. Scientists synthesized Fe-HA gels in the laboratory and explored 

processing conditions such as crosslink density, pH, and mixing time, in order to span the 

spectrum of possible product variations. They studied its physical properties e.g., 

wettability or ability to spread or get between two surfaces, as well as chemical 

properties, such as in vitro enzymatic (hyaluronidase) degradation products and half-life 

(t 1⁄2). Through these studies, we were able to gain a thorough understanding of the 

chemical and physical properties that affect the safety and effectiveness of a device 

incorporating the material. 

The research of this laboratory provided FDA with scientific tools to detect early 

evidences of safety problems by improving product tests. While these and other findings 

have resulted from work performed because of problems of one particular device and one 

material, researchers believe the issues and properties of the material can possibly be 

applied to other soft polymeric materials and hydrogels that are deployed into and onto 

the body. 
19

Interlaboratory Testing of ASTM F1717, Standard Test Methods for Spinal Implant 

Constructs in a Vertebrectomy Model (Solid Mechanics Laboratory, Division of Solid 

and Fluid Mechanics)

Spinal implant constructs consist of numerous components such as pedicle screws, hooks, 

rods, connectors, and plates that are used to immobilize and stabilize the spine until 

fusion occurs between the vertebrae. Mechanical characterization of spinal implants is 

prescribed in ASTM F1717 Standard Test Methods for Spinal Implant Constructs in a 

Vertebrectomy Model, which outlines static and dynamic test methods for compression 

bending, torsion, and tension bending. This method is recognized by FDA and is a 

routine part of submissions for new devices. Though the test method has been on the 

books for many years, round-robin testing to illustrate expected variability in results 

within and between laboratories had never been conducted, making it more difficult for 

reviewers to interpret test results both for a single device and in comparisons between 

devices. FDA encouraged ASTM to conduct an interlaboratory study to collect data to 

generate a precision and bias statement for the method. DSFM was one of six facilities 

across the country that participated in the interlaboratory study. Engineers within DSFM 

performed static torsion and compression bending tests, and provided valuable feedback 

to the ASTM sub-committee as first-time users of the test method which facilitates 

further refinement of the standard. Additionally, DSFM provided hands-on training in 

conducting this test method to 15 engineers, 3 medical officers, and 1 biologist within the 

Orthopedic Spine Devices Branch in the Office of Device Evaluation who evaluate test 

data generated from this standard to help make recommendations on device performance 

in marketing applications. Having first-hand experience in a test method provides 

invaluable information about the actual mechanics of conducting a test that can be used in 

assessing results for new devices.

In vitro Thrombogenicity Testing of Blood-Contacting Materials and Medical Devices 

(Fluid Dynamics Laboratory, Division of Solid and Fluid Mechanics)

Patient complications due to blood clots and embolization are major clinical concerns 

associated with many blood-contacting devices. Due to the lack of widely accepted in 

vitro thrombosis test methods to evaluate medical devices, FDA and industry currently 

rely on costly and time-consuming animal studies for evaluating device thrombogenicity. 

To address this issue, OSEL scientists are working with experts within the FDA, the 

medical device community, and academia to develop in vitro test methods for 

thrombogenicity evaluation of medical materials and devices. One major challenge in 

developing in vitro thrombogenicity test methods is to control the coagulability of the 

blood so that it remains stable over the testing period but clots when exposed to 

thrombogenic conditions. To this end, OSEL scientists comparatively tested blood from 
20

four different species (human, bovine, ovine, and porcine) to determine how 

anticoagulation conditions impact thrombus formation during dynamic testing with a 

recirculating blood flow loop. 

In the experiments, the clotting potential of the blood, which was originally 

anticoagulated with acid-citrate-dextrose solution A (ACDA) to prevent clotting during 

withdrawal and shipment, was controlled by adding calcium and heparin to a

concentration of 1 to 2 U/ml. Over the testing period, the blood was stable and did not 

clot under static conditions for any of the species. However, the preliminary 

results showed that when the blood was subjected to high shear stresses in a stenotic flow 

model, various sizes of thrombi formed with human, ovine, and porcine blood; but only 

minimal thrombi formed with bovine blood. These results suggest that recalcified 

ACDA-anticoagulated blood treated with low-concentration heparin may be useful for in 

vitro thrombosis evaluations of medical devices but also that appropriate anticoagulation 

levels need to be tailored for blood from different species. In addition to laboratory 

research, OSEL scientists are also actively working with national and international 

standards organizations to develop and revise several hemocompatibility testing 

standards, including the widely-used ISO 10993-4 standard (“Selection of tests for 

interaction with blood”). The results of this work were presented at the 2011 Annual 

Meeting of the American Society of Artificial Internal Organs.

Medical Device Electromagnetic Compatibility (EMC) with Radio Frequency 

Identification (RFID) (Electromagnetic and Wireless Laboratory, Division of Physics)

The OSEL Division of Physics has a long history of discovering electromagnetic (EM) 

sources that interfere with medical devices; RFID is no exception. RFID (radio 

frequency identification) is an automatic identification method that can read a tag from 

several meters away. Unlike conventional barcodes, RFID does not require line of sight 

between the reader and tags. To achieve this, an RFID reader transmits radio frequency 

(RF) energy to a tag. This tag then uses RF energy to respond to the reader with its 

unique identifying information. FDA is promoting RFID technology to track and trace 

drugs through the supply chain to help mitigate counterfeit drugs. RFID is also used 

widely in many hospitals to track the location of medical devices. In previous years, FDA 

demonstrated adverse effects of RFID readers on a number of implantable cardiac 

pacemakers. In 2011 FDA researchers, in collaboration with industry, tested the effects of 

RFID readers on implantable neurostimulators. One effect seen was a loss of proper 

stimulation from one model of neurostimulator when exposed to low-frequency RFID 

readers. The research conducted is entirely proactive, as there have been no credible 

incident reports of neurostimulators being adversely affected by RFID to this date. The 

study was published in the Biomedical Engineering Online (October 2011). FDA and 

industry are using the information collected in the study to develop RFID EMC 

(electromagnetic compatibility) standards that currently do not exist. These standards 
21

assist and speed up the review process for pre-market submissions. Additionally, the 

information and experiences learned about RFID technology have assisted CDRH in the 

pre-market approval of RFID-enabled medical devices.

New Left Bundle Branch Block Criteria to Predict Patient Benefit (Biophysics 

Laboratory, Division of Physics)

In the past 2 years, there have been two FDA panel meetings to seek input on new PMA 

applications to expand the indications for cardiac resynchronization therapy. Key 

discussions have revolved around the paucity of evidence regarding the appropriate QRS 

duration in the presence of left bundle branch block for CRT to be indicated. In response, 

the Biophysics Laboratory, led by Dr. David Strauss has completed and continues to 

pursue a series of studies to improve biomarkers to diagnose left bundle branch block and 

to predict which patients will benefit from CRT. In 2011, Dr. Strauss published new 

electrocardiographic criteria to diagnose left bundle branch block in the American 

Journal of Cardiology. Dr. Loriano Galeotti, also from the Biophysics Laboratory, has 

subsequently studied the sensitivity and specificity of the new LBBB criteria using 

computer simulations of heart activation and has shown that the criteria have equivalent 

sensitivity with greatly improved specificity compared to conventional criteria. This was

presented at an international scientific conference in April 2012. Researcher Zak Loring

has evaluated the ability of the new criteria to predict benefit from CRT as a sub-study to 

the pivotal MADIT-CRT trial. In addition, Dr. Strauss evaluated the presence of scarring 

by cardiac MRI in patients with left vs. right bundle branch block and presented the 

results at the American Heart Association in November 2011. This research on CRT and 

left bundle branch block may change professional society guidelines and FDA labeling 

for which patients should receive cardiac resynchronization therapy. This will prevent 

unnecessary devices from being implanted and reduce patient harm and complications. 

Quality System Inspection (Software: Regulatory Support and Research, Division of 

Electrical and Software Engineering) 

In 2011, biomedical software engineer Lisa Simone provided her expertise as part of an 

inspection team at a medical device manufacturer’s facility. DESE was called upon to 

collaborate in this challenging inspection to assist field investigators in identifying 

specific deficiencies in the firm’s quality management system. In medical devices that 

contain software, it can be extremely difficult to assess if a firm follows their processes 

for design controls, especially in the areas of validation, risk/hazard analysis, and design 

changes. 

In collaboration with the inspection team, Ms.Simone identified a trend in customer 

complaints that the firm had not been aware of. This trend involved incorrect or missing 
22

patient results in a laboratory information system, and incorrect or missing notifications 

to clinicians that test results were out of range. These types of failures can directly lead to 

patient harm or death if inappropriate drug dosing (too little or too much) or clinical 

decisions are made based on incorrect information. At the start of the inspection, the firm 

had 13 open complaints in this area, 10 of which had not been assessed for risk-to-health, 

safety or for accountability to FDA for an average of 287 days. Ms. Simone pinpointed 

critical software files and identified several coding defects which directly caused many of 

these customer complaints. Some defects were basic violations of software coding 

practices, while others were new defects that were introduced during the correction of 

previous defects. As a result of the investigation and her analysis, the firm issued 2

Correction and Removals, and 11 Class II recalls. 

Simulation Codes for Medical Imaging (Medical Imaging Laboratory, Division of 

Imaging and Applied Mathematics)

Investigators in DIAM use computer simulations to answer critical questions regarding 

the safety and efficacy of new medical imaging products without resource-intensive preclinical and clinical studies. Since creating open-access our simulation codes to the wider 

medical imaging research community through a free online repository 

(http://code.google.com/hosting/search?q=label:DIAM), the web pages have been visited 

more than 4000 times and the software tools have been downloaded more than 500 times 

from more than 80 different countries. These software tools are facilitating investigations 

on new approaches for the design and optimization of medical imaging systems. 

Successful results from various research groups have already been presented at 

international scientific meetings such as the upcoming 2012 SPIE Medical Imaging 

Symposium. 

Fig 5 
23

Software and Book Developed for Nerve Excitation Model (Biophysics Laboratory, 

Division of Physics)

J. Patrick Reilly and Alan Diamant, two OSEL research fellows, are publishing a book 

titled, Electrostimulation: Theory, Applications, and Computational Model. The book is 

accompanied by a public release of the source code and executables of their “Spatially 

Extended Nonlinear Node” (SENN) model that is described in the book. The software 

and a brief user’s guide will be offered as a free download on a web site maintained by 

the publisher, Artech House. The applications for electrical stimulation device and 

associated software are broad and important. The book and software provide an 

intuitively simple model for estimating electrical dose at the site of nerve or muscle 

excitation. The method, now available to the public, is of value to both reviewers and 

researchers. Electrical dosimetry for electrical stimulation devices is evaluated by 

Division of Physics staff, typically, on a case-by-case basis. The SENN model is 

universally applicable and provides an estimate for effective electrical stimulation 

without excessive stimulation. The book describes the “Threshold Factor” using the 

SENN neuro-electric model to give a numerical rating of any form of electrical 

stimulation. The “Threshold Factor” correlates with the volume of tissue containing 

neurons that may be excited by an electrical stimulus. The model and book unify our 

understanding of electrical dose. A large number of medical devices employ electrical 

stimulation of the spinal cord, deep brain, cerebral cortex, peripheral nerve, and auditory 

nerve, and are used in cardiac pacemakers, electrical defibrillators, muscle stimulators 

and magnetic stimulators. The earliest application of the SENN model was used to set 

MRI safety limits for induced electrical stimulation, and this was done in collaboration 

with CDRH. Now this useful model has been converted to one that can be easily used on 

a personal computer, along with a book to guide its use. 

Division Descriptions

DIVISION OF BIOLOGY (DB)

DB participates in the Center's mission by conducting research, participating in device 

review activities, developing consensus standards both domestic and international, 

developing regulatory guidance, testing forensic and regulatory samples, and providing 

educational programs in the area of biological sciences. Specifically, DB conducts 

research to support the Center’s mission to assure the safety and effectiveness and 

promote the improvement of medical devices in the areas of biological risk assessment, 

biosensors/nanotechnology, genomic and genetic technologies, infection control and 
24

sterility, tissue-device interactions, toxicity/biocompatibility, and radiation bioeffects.

Through laboratory studies, researchers evaluate the potential adverse effects of medical 

devices on host biological systems and, in collaboration with engineering divisions, 

identify the source and impact of product degradation on organ systems both under acute 

and chronic conditions. The Division staff develops measurements methods and 

analytical procedures to characterize and evaluate devices and products, studies 

molecular and cellular mechanisms and bioeffects of biomaterials, and supports the 

Center’s enforcement and product testing activities. 

The DB staff members are primarily biologists, chemists, and biomaterials scientists. 

Laboratories 

· Biomolecular Mechanisms 

· Cardiovascular and Interventional Therapies

· Emerging Biosensors and Biotechnologies

· Infection Control

· Toxicology and Biocompatibility 

DIVISION OF CHEMISTRY AND MATERIALS SCIENCES (DCMS)

DCMS participates in the Center's mission by conducting research, participating in 

device review activities, developing consensus standards both domestic and international, 

developing regulatory guidance, testing forensic and regulatory samples, and providing 

educational programs in the area of chemistry and materials sciences. Specifically, the 

DCMS focus is on developing experimental data, test methods and protocols for 

regulatory and scientific activities involving multicomponent mass transfer, reaction 

kinetics, absorption and swelling of network polymers, polymer processing, modeling of 

physiological processes, and materials degradation. Research activities in the division 

include synthesis and characterization of polymeric and nanocomposite materials; 

computational modeling of microstructures and microstructure development; evaluating 

drug and small-molecule elution, diffusion, and leaching from device materials; 

developing sensor evaluation protocols; measuring and modeling structural transitions 

and phase stability; hydrogel and biopolymer synthesis and characterization; and shelflife and service life prediction. DCMS tests the performance of chemical processes of 

importance to medical devices, such as mass transfer through membranes used in dialysis 

and blood oxygenation, and manufacturing processes used to fabricate materials and 

evaluate tools and protocols for device performance. 

The technical disciplines of the DCMS staff include physical chemistry, analytical 

chemistry, polymer science, pharmacology, materials science, materials engineering, 

biomedical engineering, and chemical engineering. 
25

Laboratories

· Active Materials

· Chemical Contamination 

· Materials Performance 

DIVISION OF ELECTRICAL AND SOFTWARE ENGINEERING (DESE)

DESE participates in the Center's mission by conducting research, participating in device 

review activities, developing consensus standards both domestic and international, 

developing regulatory guidance, testing forensic and regulatory samples, and providing 

educational programs in the area of electrical engineering and software. Specifically, the 

DESE works in the application of electronics, software engineering, and systems 

engineering body of knowledge to the regulation of medical devices and electronic 

products that emit radiation. The Division addresses the cutting edge of medical devices 

through all phases of the product life cycle and all aspects of the product manufacturer’s 

business, from research and development through procurement, production, and ongoing 

customer support. DCMS hosts the following resources and capabilities: analog and 

digital circuit design, data acquisition and display, embedded microprocessor and PCbased systems, software-based virtual instruments, quality management and risk 

management as applicable to electronics and software, testing for hazards arising from 

the use of electrical and electronic technology in medical products, and electronic design 

including components, circuits, and analytical techniques for controlling high voltages 

and/or currents.

DESE staff members are primarily electronics and electrical engineers, physicists, 

biomedical engineers, and general engineers.

Laboratories

· Medical Electronics 

· Software (Regulatory Support and Research) 

DIVISION OF IMAGING AND APPLIED MATHEMATICS (DIAM)

DIAM participates in the Center's mission by conducting research, participating in device 

review activities, developing consensus standards both domestic and international, 

developing regulatory guidance, testing forensic and regulatory samples, and providing 

educational programs in the area of medical imaging and applied mathematics. 

Specifically, DIAM provides scientific expertise and carries out a program of applied 

research in support of CDRH regulation of radiation-emitting products, medical imaging 
26

systems, and other devices utilizing computer-assisted diagnostic technologies. Medical 

imaging research encompasses ionizing and non-ionizing radiation from data capture 

through image display and observer performance. The computer-assisted diagnostics 

work of DIAM is focused on the appropriate mathematical evaluation methodologies for 

sophisticated computational algorithms used to aid medical practitioners interpret 

diagnostic device results. The Division is charged with developing and disseminating 

performance assessment methodology appropriate to these modalities. DIAM operates a 

calibration laboratory for ionizing radiation detection instruments and participates in a 

full range of programs in support of the Public Law 90-602 mission of the Center. 

DIAM staff members are primarily physicists, mathematicians, and physical science 

technicians. 

Laboratories

· Image Analysis

· Imaging Physics 

· Ionizing Radiation Metrology 

DIVISION OF PHYSICS (DP)

DP participates in the Center's mission by conducting research, participating in device 

review activities, developing consensus standards both domestic and international, 

developing regulatory guidance, testing forensic and regulatory samples, and providing 

educational programs in the area of physics. Specifically, DP conducts research and 

engineering studies to support the Center’s mission to assure the safety and effectiveness

of medical devices and electronic products, and to promote their improvement. Scientific 

and technical specialties in the division include optical physics and metrology, sensors, 

fiber optics, electromagnetics, electromagnetic compatibility and electromagnetic 

interference, biophysics, functional imaging, cardiac, electrophysiology, neuroscience, 

and minimally invasive optical and electromagnetic technologies. The Division develops 

measurement methods, instrument calibration capabilities and analytical procedures to 

characterize and evaluate devices and products such as computational modeling, and 

supports the Center’s enforcement and product testing activities. DP evaluates 

interactions of electromagnetic and optical energy with matter, analyzes implications for 

the safety and effectiveness of devices and products, and develops and evaluates 

procedures for minimizing or optimizing human exposure from such devices. 

The technical disciplines of DP staff include physics, mathematics, biophysics, 

biomedical engineering, electronics, neuroscience, and general engineering. A newly 

formed laboratory is in human-device interfaces. The Human-Device Interface 

Laboratory is designed to support research in human factors and medical device use. The 
27

facility will examine the people who interact with medical devices, the ways they use

devices, and the environments or settings in which they use them.

Laboratories

· Biophysics 

· Electromagnetic and Wireless Technologies 

· Functional Performance (Human) Device Interface 

· Optical Diagnostic Devices 

· Optical Therapeutics and Medical Nanobiophotonics

DIVISION OF SOLID AND FLUID MECHANICS (DSFM)

DSFM participates in the Center's mission by conducting research, participating in device 

review activities, developing consensus standards both domestic and international, 

developing regulatory guidance, testing forensic and regulatory samples, and providing 

educational programs in the area of solid and fluid mechanics. Specifically, the core 

responsibilities of this division involve issues for which mechanical interactions or 

transport are of primary concern, such as those involving motion; structural support, 

stabilization, or vibrations; device and material mechanical integrity; materials durability; 

and biologically relevant parameters of device and materials. The Division has expertise 

in the areas of fluid dynamics, solid mechanics and materials, acoustics and ultrasonics. 

DSFM develops measurement methods, instrument calibration capabilities, and analytical 

procedures to characterize and evaluate devices, device materials, and products, and 

supports the Center's enforcement and product testing activities. DSFM staff also 

evaluate interactions of ultrasound energy with matter and the implications of these 

interactions on the safety and effectiveness of devices and products. 

Technical disciplines of the DSFM staff include mechanical engineering, materials 

science, biomedical engineering, general engineering, and physics. 

Laboratories

· Fluid Dynamics 

· Solid Mechanics 

· Ultrasonics 

MANAGEMENT SUPPORT STAFF (MSS)

MSS provides leadership and support to the Office of the Director, Division Directors, 

and laboratory professionals on all administrative, general management, and knowledge 

management issues. MSS is responsible for planning, developing, and implementing 
28

Center and OSEL programmatic matters concerning financial management, personnel, 

procurement, contracts, inter-agency agreements, employee training, and facilities.

MSS is also tasked with managing and administering OSEL resources designed to 

support on-going programs. The staff ensures the proper distribution of operating and 

payroll dollars, facility plans, procurement and property, travel requests and ADP needs. 

MSS advises the Office of the Director on potential issues that may affect resources, 

staffing, and management issues to comply with policies and avoid potential conflicts. In 

addition, MSS directs and conducts special assignments or projects for the Center as well 

as the Office Director. 
29

Office of Science and Engineering Laboratories

Research Laboratories and Selected 2011 Accomplishments 

Biomolecular Mechanisms Laboratory (Division of Biology) 

The Biomolecular Mechanisms Laboratory conducts research applying new technologies 

in the areas of genetics and immunology as related to device and diagnostic development 

(translational science) and safety assessment. Laboratory projects facilitate the 

development of expertise necessary for authoritative consultation on novel, controversial, 

and complex medical devices.

Specific goals include the following:

· Investigating potential biological safety problems with new biomaterials and 

devices that are unlikely to be addressed by industry or academia

· Understanding the biological basis of adverse events reported for 

marketed medical devices

· Providing the research base for new performance standards for industry and 

CDRH reviewers

Current research areas address the following:

1. Biocompatibility issues affecting approval of new devices and nano-sized 

materials; 

2. Basic studies in vascular biology relevant to cardiovascular device adverse events; 

3. Medical Counter Measures studies on the rapid detection and threat mitigation of 

bio-terror agents, including Ebola virus; 

4. Issues in the acceptance of genetic analyses related to personalized medicine, 

including detection of genetic biomarkers and whole genome sequencing; 

5. Review of cross-center future products such as drug or biologic/device 

combination products. 

These studies harmonize medical device review issues and address the Center’s 

regulatory need for methods to ensure the safety and efficacy of medical devices and 

diagnostic tests. To achieve these goals studies are focused on 1) understanding the basis 

for adverse biological reactions at the molecular and cellular levels, and 2) practical 

innovations that incorporate new technologies. 

Accomplishments 
30

Genetic Toxicology Assay Development for Small Medical Devices and Nanomaterials

Device safety assessment includes testing for genetic interactions as hazard identification 

for cancer risk. The most common assays used world-wide are bacterial mutation assays. 

However, biocompatibility assays generally require prohibitive numbers of small medical 

devices such as cardiovascular stents or dental implants in order to test a standard 

quantity of material. Laboratory staff have developed and tested alternative methods that 

require one-fifth to one-tenth the amount of material required for the standard bacterial 

assays, while maintaining assay sensitivity. These assays may also be problematic for 

assessing metal nanoparticles, which may be excluded from the cells. Biomolecular 

Mechanisms scientists are thus investigating the utility of this assay for assessing

nanomaterials and investigating the effect of nanomaterials as inhibitors or facilitators of 

the detection of genotoxins in combination. 

Genetic Toxicology Expertise

Staff performed more than 30 formal consults in the areas of genetic toxicology and 

chaired the CDRH Genetic Toxicology Guidance document committee and the FDA 

wide GeneTox Network. The Network hosted outside speakers developing new assays for 

genetic toxicology assessment and employing Next Gen Sequencing technologies. Three 

publications in genetic toxicology addressed the integration of new technologies, the 

analysis of the causes of hereditary genetic damage, and the development of a new in vivo

genotoxicicity assay that can be performed in humans as well as in experimental animals. 

Biophysics Laboratory (Division of Physics) 

The Biophysics Laboratory covers a broad range of expertise spanning cardiac 

electrophysiology, retinal imaging, peripheral nerve physiology, neural implants effects, 

quantitative MRI and MR thermometry.

Medical devices that rely on electrophysiology and electrical stimulation for safety and 

efficacy cut across all medical specialties. The most important examples are devices that 

work in the heart and nervous system including the following: cardiac pacemakers, 

defibrillators, retinal stimulators for blindness, brain stimulators (for Parkinson’s disease, 

pain, motor function, hearing), electroconvulsive therapy, magnetic brain stimulation, 

cochlear implants, middle ear hearing devices, spinal cord stimulators, vagus nerve 

stimulators, and peripheral nerve stimulators (including those for locomotion, breathing, 

bladder and bowel control). The less obvious examples are devices for the electrical 

detection of cancer (from breast, colon and cervix), the transdermal electrical extraction 

of glucose for monitoring, and a number of “complementary and alternative medicine” 
31

devices. The scientific discipline of electrophysiology forms a unified basis for the 

scientific evaluation of all of these devices. The scientific issues involve the basic 

electrophysiology of a number of body systems and the biomedical engineering of the 

devices.

In the area of MRI technology, many of the advanced MRI techniques are cleared for 

clinical use but lack standardization. These include functional BOLD MRI, Diffusion 

Tensor imaging and Dynamic contrast enhanced imaging. The research involves 

understanding sources of variability in these methods to facilitate the adoption of these 

methods as imaging-based biomarkers in clinical trials. Much of the work pertains to 

developing suitable phantoms and assessing reproducibility. In addition to the research in 

MRI-based biomarkers, the laboratory is also involved in other MRI-related medical 

device research such as the analysis of adverse events, and thermometry. This expertise 

also directly supports the regulatory activities pertaining to the pre-market review of MRI 

devices.

The research in this laboratory ranges from work directly applied to a single device type 

(the retinal stimulator), to broader work that is relevant to a class of devices (cardiac 

stimulators for treating arrhythmias and heart failure), and to far-reaching work on the 

development of optical stimulation of excitable tissue (supported extramurally). In 

addition to these areas of research, this laboratory is heavily involved in direct regulatory 

activities with staff performing as lead reviewers, expert consultants, subject matter 

experts to FDA Advisory Panels, authors of guidance documents, and the revision of 

international medical device standards.

Fig 6 Electrocardiogram is used to help diagnose and locate myocardial scar with the help of an 

anatomically based computer model.
32

Accomplishments

Novel Circuitry for Recording Neuronal Spike Activity 

A collaboration between FDA and the Naval Research Laboratory (NRL), was 

instrumental in demonstrating a new technology, invented at NRL, to record neuronal 

spike currents using large (up to 80K) microwire focal plane array imaging chips. This is 

the first report using a modified high definition imaging chip to record extracellular 

action potentials of neurons as spikes of current. Retinal ganglion cell current spike 

waveforms recorded with the array are similar to those recorded with more conventional 

AC voltage amplifiers. The method opens up the development of more novel circuitry for 

recording neuronal spike activity. The paper, titled “A novel high electrode count spike 

recording array using an 81920 pixel transimpedance amplifier-based imaging chip” by 

Lee Johnson, Ethan Cohen, Doug Ilg, Richard Klein, Perry Skeath and Dean A. Scribner, 

will appear in the Journal of Neuroscience Methods in 2012. 

Standardization of Magnetic Resonance Imaging for Clinical Endpoints in Neurology 

Drs. Sunder Rajan and David Soltysik of the Biophysics Laboratory are leading an effort 

to improve clinical endpoints for safety and effectiveness testing of medical devices. 

Functional MRI with blood-oxygen-level-dependent (BOLD) contrast is a popular, 

nonnvasive tool that can assess brain activation and can be used as a biomarker. The 

validation of BOLD as a biomarker has the potential to improve patient selection, 

treatment selection, and demonstrate treatment efficacy. It is potentially capable of 

providing objective endpoints for depression, pain, and stroke studies. Furthermore, the 

developing standards in using BOLD as a biomarker will make its use more reliable and 

efficient. In an effort coordinated by Dr. Rajan, Dr. Soltysik is studying the sources of 

variability in BOLD methods to develop phantoms to standardize the imaging. An 

indication of early success is the publication of a study that measured variability (due to 

head position) of BOLD contrast images: D.A. Soltysik, D. Thomasson, S.S. Rajan, J. 

Gonzalez-Castillo, P. DiCamillo and N. Biassou: Head-repositioning does not reduce the 

reproducibility of fMRI activation in a block-design motor task, Neuroimage 2011: vol 

56, issue 3, 1329- 1337. 

Emerging Biosensors and Biotechnology Laboratory (Division of Biology) 

The area of biosensors and biotechnology encompass a wide range of FDA-regulated 

products such as diagnostic devices, nanotechnology, implantable devices and therapeutic 

devices. The role of the Emerging Biosensors and Biotechnology Laboratory is to support 

the scientific basis for the FDA’s regulatory decision-making throughout the total product 
33

life cycle by developing independent laboratory information to answer immediate 

regulatory questions and to aid in regulatory decision-making. In addition, the laboratory 

includes as its mission the opportunity to explore new emerging technologies as potential 

areas of research in proactive investigations for future regulatory needs. The laboratory 

currently has three main focus areas: (1) Emerging biosensors, bioassays and lab-on-achip platforms for point-of-care diagnostics/personalized medicine and device safety, (2) 

nanoparticle characterization and application to diagnostic devices, and (3) radiation 

safety and novel radiation-based therapeutic agents. Staff in the Emerging Biosensors and 

Biotechnology Laboratory assess many facets of these new and emerging technologies by 

studying how device design and device components can affect performance and hence 

safety and effectiveness. The laboratory staff actively collaborate both within FDA (other 

OSEL laboratories, Office of Device Evaluation(CDRH), Center for Drug and Evaluation 

Research, Center for Food Safety and Nutrition, and the Center for Veterinary Medicine) 

with other government agencies (Naval Research Laboratory, National Cancer Institute) 

and academia (University of Maryland, University of Maryland Baltimore County, 

Northwestern University) and the research has resulted in scientific reviews of medical 

devices, peer reviewed manuscripts, invited presentations and seminars, consensus 

standards development and the development of guidance documents to assist reviewers 

and industry. 

Accomplishments 

Nanotechnology 

Nanotechnology offers 

great potential in the 

development of a vast 

array of new products 

to advance public 

health. While in vivo

nanoparticle 

applications are currently hampered by 

cytotoxicity concerns (an area the laboratory is working on in collaboration with other 

DB staff), the market for in vitro diagnostic (IVD) tests using nanoparticles is rapidly 

expanding as evident from the published literature. The resulting new technologies and 

devices are likely to be developed and FDA approval sought much sooner than for their 

in vivo-based counterparts. The use of nanoparticles-- in particular quantum dots, carbon 

nanotubes (CNTs) and gold nanoparticles--in rapid diagnostic/screening applications is 

currently being evaluated. The research is evaluating the use of nanotechnology in 

diagnostic assays and rapid screening tools. 

The studies have resulted in a number of peer-review publications and a bookchapter, 

including a review in the ACS journal Analytical Chemistry titled “Analyzing 

Fig 7 
34

Nanomaterial Bioconjugates: A Review of Current and Emerging Purification and 

Characterization Techniques” that made the “top 10 list of most read articles” during the 

second quarter of 2011 for Analytical Chemistry and the “top 20 list of most read 

articles” for the previous 12 months. Knowledge gained from these studies and those of 

others has been used to help draft a guidance document currently under review at the 

Center level; “Draft Guidance for Industry and Food and Drug Administration Staff. 

Guidance Document: Medical Devices Incorporating Nanotechnology”, in which a 

number of DB staff took lead writing roles. DB staff have also been actively involved in 

developing a syllabus for a comprehensive nanotechnology training program to be 

offered to FDA reviewers titled “FDA Applied Sciences Course in Nanotechnology.”

Lab-on-a-chip (LOC) 

Point-of-care (POC) in vitro diagnostics (IVD) has the potential to transition diagnosis 

from a centralized laboratory into the doctors’ office to provide the patient and physician 

with more timely diagnosis and therefore treatment and represent the next generation of 

medical diagnostic devices regulated by FDA. Lab-on-a-chip (LOC) technologies, in 

particular, will play a key role in this transition and incorporate advances in many areas 

of science including materials, electronics, optics, reagents and nanotechnology. 

Understanding the many aspects of these POC IVD technologies, including signal 

generation and transduction mechanisms, bioconjugation and labeling techniques, 

microfluidic generation, nanotechnology, systems integration and automation and 

ultimately evaluating how these impact overall device performance will be essential to 

performing critical scientific review of such regulatory submissions, thus ensuring safe 

and effective products.

Research in this area is multi-disciplinary in nature, and as such the laboratory has 

established active collaborations with experts in other government agencies (National 

Cancer Institute and Naval Research Laboratory) and academia (University of Maryland 

and University of Maryland Baltimore County). Research in this area has resulted in ~18 

peer-review publications, including journals such as Lab-on-a-Chip, Analytical 

Chemistry, ACS Nano and Biosensors & Bioelectronics, and ~5 books/book chapters 

since 2008 for the laboratory. The hands-on expertise acquired will assist in the later 

development of test methods, guidance documents, and the review of standards for these 

types of technologies. 

Quantum Dot Nanoparticle Sensors for Heparin Contamination Screening 

The threat of economic adulteration of products by foreign manufacturers with the aim of 

increasing profits is, unfortunately, of real concern in our now globalized economy. 

Given the increasing number of medical devices and device components that are 

manufactured in foreign facilities that may be subject to less regulation prior to 

exportation, the need to provide FDA inspectors with accurate screening tools is 
35

essential. This was clearly demonstrated in 2008 when contamination of the heparin 

supply with oversulfated chondroitin sulfate (OSCS) resulted in severe anaphylactoid 

reactions in exposed patients. Current FDA-required tests for OSCS detection, while 

robust and sensitive, are expensive, require dedicated laboratories and trained personnel, 

are highly technical, and are not suitable for rapid screening of samples in the field.

The research in this area is to design rapid, inexpensive, quantitative, robust and field 

deployable high-throughput methods for detecting OSCS contamination in heparin 

samples. The project uses a quantum dot (QD) peptide-based fluorescent biosensing 

platform and is assessing its ability to detect contaminants, such as OSCS. Additionally, 

these types of platforms could be applied to the detection of alternative contaminates that 

are either proteolytic in nature (such as Botulinum Neurotoxin A) or activate protease 

activity. This project expands FDA scientific knowledge concerning the potential of QD 

nanoparticles, FRET and FRET-based protease technologies as sensing platforms using 

fluorescence transduction, which may be used to evaluate future FDA regulatory 

submissions.

Fluid Mechanics Laboratory (Division of Solid and Fluid Mechanics) 

The Laboratory of Fluid Dynamics, located in the Division of Solid and Fluid Mechanics, 

maintains a research program focused on the fundamental factors governing the 

interaction of flowing fluids with medical devices and the development of test 

methodologies to objectively characterize such interactions and their consequences.

Accomplishments 

Using Computational Fluid Dynamics to Assess Blood Damage and Medical Device 

Safety: An FDA Critical Path Initiative Project 

Computational fluid dynamics (CFD) is a subset of computer modeling used to simulate 

the flow of fluids and to calculate the physical forces acting within the fluid. CFD is 

already being used to develop and prototype blood-contacting medical devices, such as 

prosthetic heart valves and ventricular assist devices (VADs). However, the use of CFD 

to demonstrate product safety in FDA pre-market device applications and post-market 

investigations requires sufficient computational and experimental validation. This is 

especially true in the final step of the process as biological responses (e.g., red blood cell 

rupture, blood clot formation) are predicted based on the purely physical results (e.g., 

pressures, velocities, shear stresses) obtained from the computational simulations. To 

understand factors affecting the accuracy of CFD in predicting flow characteristics and 

blood damage, we conducted an interlaboratory study of a benchmark nozzle model that 

included participants from academia, industry, and the FDA. The study consisted of three 

independent parts: (1) experimental measurements of velocities in transparent models of 
36

the nozzle, (2) computational predictions of flow through the nozzle device geometry, 

and (3) experimental blood damage testing of the nozzle. The simple benchmark nozzle 

model, which mimicked the flow fields in several medical devices, consisted of a gradual 

flow constriction, a narrow throat region, and a sudden expansion region where a fluid jet 

exited the center of the nozzle with recirculation zones near the model walls. In 

collaboration with scientists at the Rochester Institute of Technology and Pennsylvania 

State University, transparent acrylic versions of the nozzle were fabricated and the fluid 

velocities and pressures were measured to provide experimental validation for the 

companion interlaboratory CFD study. 

In the second part of the project, computational modelers from around the world were 

invited to simulate the flow fields in the nozzle model prior to having access to the 

experimental velocity data. Twenty-eight groups from six different countries participated 

in the interlaboratory computational study in which the nozzle flow rate was adjusted so 

that the throat Reynolds number (Re) was varied from 500 to 6500, as in the experimental 

study. At all Re's, the largest discrepancies between the computational predictions 

appeared downstream of the throat. At Re=500, laminar simulations agreed well with 

experimental velocity data. As the Re was increased, agreement between the measured 

results and those predicted by the participants became much more variable. While choice 

of turbulent model is one factor of many that affect simulation accuracy, the analysis of 

results has helped us to develop a suite of best practices (e.g., appropriate flow model, 

inlet/outlet length, maintaining mass conservation) for using CFD in medical device 

evaluations that is impacting both the development of standards and an FDA Guidance 

Document on reporting computational modeling results in medical device submissions. 

The experimental flow results from the interlaboratory study were published in 2011 in 

the ASME Journal of Biomechanical Engineering. The results of the computational 

interlaboratory comparison have been accepted for 2012 publication in the Journal of 

Cardiovascular Engineering & Technology. 

Functional Performance and Device Interface Laboratory (Division of 

Physics) 

Accomplishments 

Emerging Research from the Functional Performance and Device Use Laboratory 

In 2011, the CDRH Science Prioritization Process (C-SPP) identified “Evaluating Use 

Environments and Human Factors” as one of seven major themes for the Center because 

understanding the many ways that medical device users interact with devices in typical 

environments and conditions of use is considered critical to facilitate device use and 

minimize user error. The report also cited improving health in special populations, 

including pursuing new methods of assessing persons with disabilities, as another highpriority area.
37

The Functional Performance and Device Use Laboratory was established to expand our 

understanding of how medical device design influences use errors and physical function 

during device use. As capabilities of the new laboratory were created, staff began 

collaborating with colleagues within CDRH to address regulatory science priorities 

identified in the C-SPP process. Projects in development include investigating whether 

providing speech output on infusion pumps will reduce the commission and increase the 

detection of programming errors; studying unique use-related hazards of medical device 

operation during public health emergencies and mass casualty events; experimental and 

computational modeling study of metal-on-metal hip implants to understand their 

mechanisms of wear and conditions that might contribute to device failure; and analysis 

of potential sources of use errors related to design features of floor based patient lifts. 

The breadth of these newly initiated projects focus on human factors but touch on nearly 

all of the priorities highlighted by the C-SPP. Results of these projects have great 

potential to inform pre-market review and post-market surveillance strategies and 

development of guidance and standards for the manufacturing of safe and effective 

medical devices. 

Infection Control Laboratory (Division of Biology) 

The Laboratory of Infection Control is an interconnected program of laboratory research 

that provides consults for medical device-associated infections/sterility, and biological 

evaluation of medical devices (biocompatibility) for premarket submissions (510(k), IDE, 

PMA) and postmarket submissions (30-Day notice change for PMA), public health 

notifications, safety alerts, recalls, Health Hazard Evaluations, Health Risk Assessments, 

522 surveillance studies, field inspections, develop or update regulatory guidance 

documents, national and international standards designed to promote a scientific basis for 

pre-market and post-market regulatory decision making in CDRH. 

Members of the Infection Control Laboratory have accomplished much in research and 

regulatory arenas regarding biological evaluation of medical devices and in 

sterility/infection control. Both of these areas are issues that cover nearly all medical 

devices and have major public health impact.

Accomplishments 

Infection Control and Device Design

The influence of device design (physical design, materials used in fabrication) in 

reprocessing single-use and reusable medical devices to prevent transmission of 

infectious agents is one of the critical issues the laboratory is currently studying. 
38

Reprocessing reusable devices is a multi-step process designed to maximize patient 

safety. Cleaning the device is a critical first step. A properly cleaned device should be 

free of contaminants such as biological matter (e.g., blood, tissue, mucus, etc.) and nonbiological materials (e.g., lubricants, detergents, brush bristles, etc.). The presence of 

such materials can potentially compromise the effectiveness of disinfection or 

sterilization processes. Several published reports have documented the transmission of 

infectious material from improperly reprocessed reusable medical devices. 

Incidents of improperly cleaned (e.g., arthroscopic shaver handles, endoscopes) and/or 

disinfected (e.g. endoscopes) reusable devices have prompted FDA to issue Safety 

Communications, Alerts and Notices (Medical Devices) and to require manufacturers to 

validate the cleaning of reusable devices with test soils and quantitative measurements of 

residual soils after cleaning. In the past, an acceptable assessment of cleanliness was a 

visual examination of the device to ensure it was free of contaminants. However, modern 

devices are increasing in complexity with internal design features that are easily visible to 

the naked eye, such as narrow opaque lumens, hinges, stopcocks, protective sheaths, 

rough surfaces, etc. Thus, the design of reusable devices (physical design, use of 

materials to fabricate) can influence infection control. 

The laboratory is presently developing methods to detect and remove the chemical 

warfare agent Ricin, a natural toxin, on various medical device surfaces. Ricin is 

relatively easy to make or obtain, is stable, and may contaminate reusable devices either 

deliberately or accidentally, peanut lectin is used as a surrogate of Ricin. The laboratory 

data showed the following: 

· Reverse osmosis system can remove small toxins from water

· Commercially available wipes containing sodium hypochlorite as the active 

ingredient rapidly denatures peanut lectin. 

Laboratory staff are involved with all Center discussions concerning reprocessing of 

reusable medical devices and infection control in general, including the following: 

· Helped draft the guidance document “Processing/Reprocessing Medical Devices 

in Health Care Settings: Validation Methods and Labeling” (May 2011) 

· Gave presentations on the subject of medical device reprocessing and use – the

FDA Public Workshop on Reprocessing Reusable Medical Devices (June 8-9, 

2011), and FDA’s Perspective of “Clean” at the Association for the Advancement 

of Medical Instrumentation (AAMI) and FDA Summit: Medical Device 

Reprocessing (October 11-12, 2011). 
39

Medical Electronics Laboratory (Division of Electronics and Software 

Engineering) 

Accomplishments 

Medical Device “Flight Data Recording” and Animation 

Safety critical devices such as those found in the transportation and power industries 

routinely record operational data via “flight data recorders” or data loggers to enable 

analysis of adverse events. Here, the data can be used to help determine the cause of the 

adverse event and subsequently to eliminate or mitigate future events. The data can also 

be used to assess and optimize device performance issues under different use and 

environmental conditions. The recordings can also serve another purpose, which is to 

help verify that design changes take into account adverse event scenarios and mitigate 

them properly by playing them back as test cases.

As medical devices become more complex and interoperable, so too is the need for 

recording medical device data. To address this issue we are developing a set of “flight 

data recording” requirements that can be used in medical devices (or networks of medical 

devices) to help eliminate or mitigate future adverse events. 

It is not enough to be able to record adverse event data. There is a need to “play back” or 

animate the data in a manner that is helpful to investigators. This issue becomes 

particularly complex for interoperable devices. Here, it may be necessary to integrate and 

animate data from multiple medical device flight data recorders to gain a comprehensive 

understanding of an adverse event. Researchers are developing techniques to perform this 

animation integration.

Optical Diagnostic Devices Laboratory (Division of Physics) 

The rapid proliferation of novel diagnostic medical devices employing minimally or 

noninvasive optical technology is revolutionizing modern health care. These devices now 

perform a variety of critical in vivo tasks in the clinic, such as oximetry monitoring, 

atherosclerotic plaque assessment, high resolution retinal imaging, and early detection of 

lung, cervical and gastrointestinal cancers. These systems are based on a variety of 

optical mechanisms including fluorescence, reflectance and coherence-domain imaging. 

Given their increasing complexity, optical technologies represent a significant new 

regulatory challenge to FDA. There are distinct gaps in understanding the biophysical 

mechanisms of action, device- and tissue-specific light propagation effects, and tissue 

damage by ultraviolet, visible and infrared radiation. Basic mechanism studies are needed 

to facilitate the development of relevant evaluation criteria early in the regulatory 
40

process, thus enabling thorough and swift reviews of cutting-edge optical technologies. 

The Optical Diagnostic Devices laboratory works to generate fundamental data through 

studies of light-tissue interaction mechanisms, device performance and tissue safety for a 

variety of optical technologies. Furthermore, the laboratory is developing phantom-based

performance test methods and advanced computational models of light propagation in 

tissue to elucidate device working mechanisms and facilitate the device review process. 

This program is located within the Division of Physics (DP).

Accomplishments

Imaging Neuronal Tissue Directly below a Stimulus Electrode in Real-Time

A common problem in determining neural stimulation safety at FDA is the lack of 

established scientific techniques to study the effects of electrical stimulation on the 

neurons directly below a stimulus electrode in real time. This is because most stimulus 

electrodes are made of opaque metals that block conventional optical imaging methods. 

Noting that plastic tubes made of Teflon fluoropolymers became optically transparent in 

saline, FDA developed a method to image neuronal tissue directly below a stimulation 

electrode using optical coherence tomography (OCT). A collaboration between Dr. Ethan 

Cohen of the Biophysics Laboratory and Anant Agrawal and Dr. Josh Pfefer of the 

Optical Diagnostic Devices Laboratory (both laboratories are in the Division of Physics), 

resulted in discovery of how to image the retinal tissue layers swelling in response to epiretinal electrical pulse train stimulation over the course of time, determining what levels 

of stimulation were safe for the retina, and documenting changes to the optical properties 

of the tissue. The paper titled “Optical coherence tomography imaging of retinal damage 

in real time under a stimulus electrode” by Ethan Cohen, Anant Agrawal, Megan 

Connors, Barry Hansen, Hamid Charkhkar, and T. Joshua Pfefer was published in 2011 

in the Journal of Neural Engineering. 

Optical Therapeutics and Medical Nanophotonics Laboratory (Division of 

Physics)

Minimally invasive biophotonics techniques and devices have been recently developed as 

potential alternatives to conventional medical methods for diagnosing, monitoring and 

treating a variety of diseases, drug discovery, proteomics, and environmental detection of 

biological agents. These technologies offer a non-contact, effective, fast and painless way 

for sensing and monitoring various biomedical quantities. Medical devices utilizing 

minimally invasive biophotonics technology are rapidly finding their way into the 

mainstream for early disease diagnosis and improved patient acceptance and comfort. 

Optical therapeutics approaches are being proposed that use high-intensity ultra-short 

laser radiation, precise delivery fiber optics and near/mid-infrared biosensing and 

monitoring. CDRH recognizes the need to prepare for evaluating devices being 
41

developed to optically diagnose and treat various diseases, including pre-cancerous and 

cancerous conditions. 

The Optical Therapeutics and Medical Nanophotonics(OTMN) Laboratory of 

CDRH/OSEL’s Division of Physics is responsible for providing and maintaining state-ofthe-art knowledge and expertise in the biophotonics, nanobiophotonics, biomedical optics 

and medical laser field to assist the Center and Agency in evaluating new medical 

therapeutics devices that employ the latest minimally invasive optical technologies. The 

OTMN Laboratory also assists with the regulation of hazardous optical and laser 

radiation emissions potentially harmful to the general population, and with the latest 

measurement devices to evaluate new optical therapeutics products. OTMN Laboratory 

research and regulatory-related projects are focused in the following major areas:

1. Evaluating safety and effectiveness of new optical therapeutics technologies and 

devices concerning critical optical parameters and safety issues related to various 

medical therapeutic lasers, fiber-optic technologies, and new therapeutic 

monitoring and biosensing systems. 

2. Developing standard test methods and test protocols for laboratory evaluation of 

fundamental optical radiation characteristics including spectral (from the 

ultraviolet to mid-infrared), timescale (from millisecond to femtosecond), and 

spatial parameters of key coherent (lasers) and non-coherent light sources, and 

also fiber-optic components used in recently developed optical therapeutics 

devices. 
42

3. Studying working light-tissue interaction mechanisms for optimizing 

effectiveness and safety of new optical therapeutics devices, which includes 

studying light-tissue interaction mechanisms at cellular/intracellular levels using 

state-of-the-art nanobiosensing, nanoimaging and therapeutics techniques. 

Accomplishments

Novel Applications of Diagnostic X-rays in Activating a Clinical Photo-Agent Utilized in 

Photodynamic Therapies

Photodynamic therapies (PDT) for cancer treatment with photo agents possess a high 

degree of specificity for broad spectrum of aggressive cancers and may be used where 

current conventional cancer treatments such as surgery, radiation therapy, and 

chemotherapy are limited. Porphyrin-based clinical photo-agents used for PDT become 

activated in killing cancers through visible light illumination. Unfortunately, due to a 

very shallow visible light penetration depth (~2mm) in tissues, the current PDT strategy 

has largely been restricted to the treatment of surface tumors, such as the melanomas. Dr. 

Darrell Tata and Dr. Erkinay Abliz of the Division of Physics OTMN Laboratory 

reported on the development of a novel non-invasive methodology utilizing “soft” energy 

diagnostic X-rays to indirectly activate a clinical photo-agent routinely utilized in PDT: 

Photofrin II (Photo II) through X ray-induced visible light emission from biological cellsized phosphor particles. This concept was designed and tested in a human brain cancer 

cell line model. Positive findings reveal a shut-down (> 90% relative to controls) in the 

cellular metabolic activity of human brain cancer cells. The positive in-vitro bioeffect 

provides a platform for future scientific studies to provide useful endpoints for evaluating 

this optical therapeutic technique. The research was published in a paper titled, “Novel 

applications of diagnostic X-rays in activating a clinical photodynamic drug: Photofrin II 

through X-ray induced visible luminescence from ‘rare-earth’ formulated particles,” in 

the November 2011 issue of the Journal of X-ray Science and Technology.

Development of Standard Test Methods for Intraocolar Lens (IOL) Implant 

Characterization

A novel approach for precise preclinical testing intraocular lens (IOL) implants was 

developed in the OSEL/OTMN Lab (Dr. Ilko K. Ilev and Robert James) in collaboration 

with ODE (Don Calogero) and Johns Hopkins University (Yong Huang, Dr. Kang Zhang 

and Dr. Jin Kang). It is based on a noncontact common-path Fourier domain optical 

coherence tomography (OCT) sensor method for evaluating the dioptric power of IOL 

implants by precisely measuring IOL surface profiles and surface radii. This method 

ensures noncontact, accurate, and objective measurement of IOL optical power under insitu conditions. It provides CDRH and the device community with an alternative tool to 

evaluate IOL parameters with more precision, accuracy and speed, thereby enhancing the 
43

safety and effectiveness of IOL implants. The new test method was published in the 

December 2011 issue of the Journal of Biomedical Optics and was included as an 

alternative technique for IOL testing specified in the International Standards for IOL 

quality evaluation.

Software Laboratory (Division of Electrical and Software Engineering) 

The scope of this laboratory’s activities is to support CDRH pre-market and post-market 

software evaluation activities by establishing relevant in-house expertise and identifying, 

qualifying, quantifying, and communicating conformity assessment techniques and 

criteria which the Center can use to fulfill its mission. 

Software is one of the most ubiquitous enabling technologies for many, if not most, 

classes of medical devices. Devices that incorporate this technology are inherently 

extremely complex and require that engineers must be able to skillfully peel back many 

layers of abstraction from the underlying mathematical, behavioral and physical models 

that govern device operation, to their hardware and software realizations, and down to the 

physical characteristics of component parts.

Accomplishments 

Architecture Analysis 

All medical devices are built upon some form of architecture, be it hardware, software, or 

both. If the quality of the architecture is poor, it is likely that the dependability and 

performance of the device will be poor as well. DESE researchers are developing 

software architecture analysis methods that examine a devices code by deconstructing it 

into its constituent components. In this form, researchers can examine how they are 

organized and interconnected. If there are components that are overly dependent on a 

certain component or not even used, it can be a sign of current or future problems. The 

deconstruction process also facilitates analysis of design documentation. Components or 

interconnections identified from the code may not be addressed in the design 

documentation, indicating possible design specification problems. 

Software Safety Model for Infusion Pumps 

As the complexity of infusion pump design increases, so does the likelihood of its
44

Fig 9 Model-based engineering paradigm 

failure. A significant number of these failures are due to a lack of principled engineering 

practices and associated safety issues. This is particularly true in the case of software 

based systems, where failure modes are difficult to predict. To address this issue, we are 

using formal methods to investigate a means of assessing the safe execution of infusion 

pump software. 

The approach uses a model-based engineering development paradigm. In this 

methodology, software design models are derived from device safety requirements using 

executable modeling notations that simulate code execution. Once the models are 

encoded, they can be verified using rigorous mathematical methods. The verified models 

can then be used as unambiguous safety reference implementation standards against real 

world pumps.

Solid Mechanics Laboratory (Division of Solid and Fluid Mechanics) 

The goal of the Solid Mechanics Laboratory is to help CDRH understand the response of 

medical devices and their constituent materials to applied stress for both pre-market 

evaluations and post-market reported adverse events. The materials of interest include 

traditional engineering materials such as metals and polymers, but also extend to 

biological materials and those used in tissue engineered scaffolds. Though the spectrum 

of relevant materials is broad, common stress analysis principles can be applied to 

evaluate their behavior.

Accomplishments 
45

The Effects of Vertebroplasty on Strain in Adjacent Intervertebral Discs and Vertebrae 

Vertebroplasty is currently the gold standard surgical treatment for painful vertebral 

compression fractures in the spine. This minimally invasive procedure consists of 

injecting poly(methyl methacrylate) (PMMA) bone cement into a fractured vertebral 

body to stabilize the fracture and relieve associated pain. However, it has been recently 

reported that approximately 25% of the patients experience subsequent fractures within 

one year of the treatment and the vertebrae adjacent to the cemented level represented a 

majority of these new fractures (Chosa et al. 2011). These data suggest that 

vertebroplasty may negatively impact spine biomechanics, reducing the overall safety of 

this device based on the need for additional surgeries to treat the new fractures. 

Therefore, DSFM researchers conducted a biomechanical study on female cadaveric 

spines to quantify the effects of vertebroplasty on strain in adjacent intervertebral discs 

(IVD) and vertebrae (VB). The results indicated that cyclic loading significantly 

increased strains in the vertebroplasty treated specimens when compared to a control 

group that did not undergo vertebroplasty. This increased compressive strain in the 

vertebroplasty group manifested locally as approximately 11% and 3% higher strains in 

the superior adjacent IVD and VB, respectively. These results provided insight into the 

mechanical impact of vertebroplasty on adjacent spinal tissues and are useful in clinical 

treatment strategies for women who suffer painful vertebral fractures. In addition, the 

methods developed in this study may be used pre-clinically in new device submissions to 

evaluate the safety of future vertebral augmentation devices.

Toxicology and Biocompatibility Laboratory (Division of Biology) 

This is an interconnected program of laboratory research, risk assessment, and standards 

development activities designed to provide a scientific basis for regulatory decision 

making in CDRH. Researchers evaluate the potential adverse effects of medical device 

materials and chemicals, including nano-sized particles, using in vivo and in vitro

experimental models and approaches. Scientists use data to reduce uncertainties in 

assessing risks to patients exposed to physical and chemical exposures, and ultimately 

protect their health. 

Accomplishments 

Risk assessment and Biocompatibility Methods Development

A) Computational Toxicology Modeling
46

The biological safety of medical devices is typically assessed by conducting 

biocompatibility testing of an extract of the device or the device itself; however, there is 

growing interest in an alternate approach that involves characterizing the chemical 

composition of the device extract and conducting a risk assessment on the compounds 

identified in the extract. One limitation to the practical implementation of this chemical 

characterization/risk assessment approach is the lack of toxicity data for many 

compounds released from device materials. To address this need, the OSEL Laboratory 

of Toxicology and Biocompatibility is developing a new approach to assess the risk of 

these compounds in the absence of experimental data. This approach is based on the use 

of computational toxicology models, such as Quantitative Structure-Activity Relationship 

(QSAR) models and a modified version of the Threshold of Toxicological Concern 

(TTC) approach that has been used by other FDA Centers for many years. In 2011, a 

database of predicted toxicity values was developed for easy and user-friendly access by 

CDRH reviewers. This new method has already been used a number of times to assess 

the safety of medical devices and represents a promising approach for the biological 

evaluation of device materials. 

B) Identification and validation of biomarkers of kidney damage

Elevated serum creatinine and blood urea nitrogen (BUN) are typically used as indices of 

kidney injury; however, greater than 50% kidney function could be lost before elevations 

of these markers are detected. Since limitations exist with the use of these standard 

markers of kidney damage, and since early detection of even subtle renal injury is 

important for the implementation of renal protective strategies, there is a need to identify 

more sensitive biomarkers of altered renal function. Identification of new, more sensitive 

and clinically relevant biomarkers is consistent with the goals of the Critical Path 

Initiative to develop a “new product development toolkit,” including new sensitive and 

clinically relevant biomarkers of safety and effectiveness. The specific goal of this effort 

is to bridge the gap between basic and applied science and product development so that 

the safety and effectiveness of new products can be demonstrated in faster time frames, 

with more certainty, and at lower costs.

Investigators in the OSEL Laboratory of Toxicology and Biocompatibility have made 

considerable progress to identify and validate biomarkers of kidney damage. Early work 

in this area involved an evaluation of the ability of new biomarkers to detect acute kidney 

injury (AKI) at earlier time points and at lower doses of nephrotoxicants than existing 

tests. A suite of these new biomarkers has undergone a qualification process at FDA for 

use in preclinical testing, a process in which our data was used in a meta-analysis. With 

this exciting development, OSEL investigators are now focused on the use of these 

biomarkers to address regulatory issues of concern for CDRH and other FDA product 

centers. In 2011, OSEL scientists, with the National Center of Toxicology Research 

(NCTR) and Harvard University collaborators, characterized the kidney-damaging effects 

of melamine and cyanuric acid, substances used in the intentional adulteration of pet food 
47

and infant formula. With funding from the FDA’s Office of the Chief Scientist challenge 

grant program, these investigators characterized the progression of kidney and heart 

damage in a rat model of hypertension and obesity. Given the prevalence of these 

conditions in the general population, use of this rat model may provide a more clinically 

relevant approach for the preclinical safety evaluation of some devices than the use of a 

normotensive (normal blood pressure) and lean animal. 

Nanotechnology and Nanotoxicology

A) Distribution of intravenously-injected silver nanoparticles in pregnant mice 

and developing embryos 

Silver nanoparticles are used in FDA-regulated products, primarily for antimicrobial 

efficacy as catheter coatings and integrated into wound dressings. Although research 

investigating the in vivo biodistribution and toxicity of nanomaterials is increasing, very 

few studies have been conducted to evaluate nanomaterial translocation across the 

placenta and if adverse effects occur to the developing embryo. OSEL scientists, with 

collaborators from the FDA Center for Food Safety and Nutrition, George Washington 

University, Wright-Patterson AFB, and University of Florida, completed a study to 

evaluate the distribution of silver nanoparticles (10-nm and 50-nm diameter) in pregnant 

mice and embryos during gestation. The results showed an expected distribution of the 

nanoparticles primarily to the liver and spleen and that the particles do not appear to cross 

the placenta to the embryos in significant amounts. Electron microscopy, along with 

elemental analysis, indicated that the silver appears to be trapped in the mouse placenta 

and visceral yolk sac, preventing significant silver nanoparticles from reaching the 

embryo. The study resulted in a publication in 2011 in the journal Nanotoxicology.

 

Austin CA, Umbreit TH, Brown KM, Barber DS, Dair BJ, Francke-Carroll S, Feswick A, SaintLouis MA, Hikawa H, Sieben KN and Goering PL. Distribution of silver nanoparticles in 

pregnant mice and developing embryos. Nanotoxicology, E-pub ahead of print, October 2011.

Fig 10 Transmission Electron Microscopy images (Panels A, B) and an Energy Dispersive X-ray Spectroscopy spectrum 

demonstrating silver in visceral yolk sac tissue on gestation day (GD) 10 of pregnancy following I.V. injection of a 35 μg 

Ag/mouse dose of silver nanoparticles (50 nm diameter) on GDs 7, 8, and 9.
48

B) Understanding the cellular interactions with materials surface 

nanotopographies

Nanophase materials, such as nanofibers, nanotopographical surfaces, nanocoatings and 

nanocomposites are becoming very popular in the medical device industry to exploit their 

unique properties, such as better tissue integration, replacement and repair. However, 

significant basic and applied research is still needed to understand the risk associated 

with such nanoscale manipulations. OSEL scientists, with collaborators from NIST and 

NIDCR (NIH), have completed a study to understand how surface nanotopographies can 

influence the osteo-integration in medical devices, such as orthopedic and dental 

implants. The results showed convincing evidence that cells in vitro react with more 

sensitivity and specificity to nanostructured surfaces. This unique osteo-integration 

phenomenon is directly related to the nanoscale roughness provided by these 

nanotopographical surfaces. 

Fig 11 Surface roughness of etched surface were 5-times rougher as compared to un-etched surfaces (a,b). 

Representative surface profiles (c) and roughness parameters (d) of un-etched versus etched surfaces. 

(a) Un-Etched (b) Etched

-12.5

+12.5

Height (mm)

-12.5

+12.5

Height (mm)

*

*

(d)

0.21

1.06

0.28

1.30

Distance (mm)

Height (

mm)

0 10 20 30 40 50

Etched

Un-Etched

0

2

4

6

8

10
49

Ultrasonics Laboratory (Division of Solid and Fluid Mechanics) 

The Ultrasonics Laboratory continues to develop test methods and computational 

techniques for analyzing the safety and effectiveness of ultrasound ablation devices 

known as high intensity focused ultrasound (HIFU). Current accomplishments include 

developing two techniques for non-invasive measurement of high intensity fields to avoid 

sensor damage; formulating a coagulating blood mimicking fluid for use in HIFU in vitro

phantoms; characterizing the occurrence of cavitation in a tissue mimicking material 

during HIFU exposures and assessing its effect on temperature measurements; 

determining the thermal effects when ultrasound is incident on bone; and utilizing 

computational techniques to evaluate the effects of nonlinear propagation characteristic 

of HIFU beams on acoustical and thermal measurement endpoints. Further, the laboratory 

has begun studies into the neurological effects of blast waves. 

Accomplishments 

Theoretical Framework for Quantitatively Estimating Ultrasound Beam Intensities using 

Infrared Thermography

Determining intensity fields produced by high-intensity focused ultrasound (HIFU) 

devices is important in the development and pre-clinical testing of the devices, as well as 

in planning clinical procedures. Direct measurement can be challenging because the 

intense fields can cause sensor damage. An alternative approach for obtaining the 

intensity distribution is to infer it from the temperature field arising from the absorption 

of ultrasound energy in a phantom composed of tissue-mimicking material (TMM). 

Laboratory scientists have developed a theoretical model that uses infrared (IR) camera 

measurements of the temperature field as input data. Possible complications due to 

convection currents and heat diffusion are accounted for in the model. It was found that, 

when compared to the intensity field determined directly from acoustic propagation 

simulations, intensity profiles could be obtained from the simulated IR temperature data 

with an accuracy of better than 10%, at pre-focal, focal, and post-focal locations. These 

efforts will facilitate developing and characterizing an innovative and important surgical 

technology. A peer-review paper describing the methodology and results was published 

in 2011 in the Journal of the Acoustical Society of America.
50

APPENDIX A – OSEL Publications

January 1, 2011 – December 31, 2011 (ordered by publication date)

Division of Biology 

Posnack NG, Lee NH, Brown R, Sarvazyan N. Gene expression profiling of DEHP-treated 

cardiomyocytes reveals potential causes of phthalate arrhythmogenicity. Toxicology, 279(1-3):54-

64, January11, 2011. 

Balsam J, Ossandon M, Kostov Y, Bruck HA, Rasooly A. Lensless CCD-based fluorometer using 

a micromachined optical Söller collimator. Lab Chip, 11(5):941-9, March 7, 2011. 

Guerraty MA, Grant GR, Karanian JW, Chiesa OA, Pritchard WF, Davies PF. Side-specific 

expression of activated leukocyte adhesion molecule (ALCAM; CD166) in pathosusceptible 

regions of swine aortic valve endothelium. J Heart Valve Dis, 20(2):165-7, March 2011. 

Yang MH, Sun S, Kostov Y, Rasooly A. A simple 96-well microfluidic chip combined with 

visual and densitometry detection for resource-poor point of care testing. Sensors Actuators B 

Chem, 153(1):176-81, March 31, 2011. 

Sapsford KE, Granek J, Deschamps JR, Boeneman K, Blanco-Canosa JB, Dawson PE, Susumu 

K, Stewart MH, Medintz IL. Monitoring botulinum neurotoxin a activity with Peptidefunctionalized quantum dot resonance energy transfer sensors. ACS Nano, 5(4):2687-99, April 

26, 2011. 

Lynch AM, Sasaki JC, Elespuru R, Jacobson-Kram D, Thybaud V, De Boeck M, Aardema MJ, 

Aubrecht J, Benz RD, Dertinger SD, Douglas GR, White PA, Escobar PA, Fornace A Jr, Honma 

M, Naven RT, Rusling JF, Schiestl RH, Walmsley RM, Yamamura E, van Benthem J, Kim JH. 

New and emerging technologies for genotoxicity testing. Environ Mol Mutagen, 52(3):205-23, 

April 2011

Elespuru RK. Assessment of heritable genetic effects using new genetic tools and sentinels in an 

era of personalized medicine. Environ Mol Mutagen, 52(4):253-63, May 2011. 

Kattke MD, Gao EJ, Sapsford KE, Stephenson LD, Kumar A. FRET-Based Quantum Dot 

Immunoassay for Rapid and Sensitive Detection of Aspergillus amstelodami. Sensors, 

11(6):6396-410, June 2011. 

Kent M, Platt SR, Rech RR, Eagleson JS, Howerth EW, Shoff M, Fuerst PA, Booton G, 

Visvesvara GS, Schatzberg SJ. Multisystemic infection with an Acanthamoeba sp in a dog. J Am 

Vet Med Assoc, 238(11):1476-81, June 1, 2011. 

Potnis PA, Tesfamariam B, Wood SC. Induction of nicotinamide-adenine dinucleotide phosphate 

oxidase and apoptosis by biodegradable polymers in macrophages: implications for stents. J 

Cardiovasc Pharmacol, 57(6):712-20, June 2011. 
51

Sapsford KE, Tyner KM, Dair BJ, Deschamps JR, Medintz IL. Analyzing nanomaterial 

bioconjugates: a review of current and emerging purification and characterization techniques. 

Anal Chem, 83(12):4453-88, June 15, 2011. 

Yang MH, Kwon S, Kostov Y, Rasooly A, Rao G, Ghosh U. Study of the biouptake of labeled 

single-walled carbon nanotubes using fluorescence-based method. Environ Chem Lett, 9(2):235-

41, June 2011.

Jennings TL, Becker-Catania SG, Triulzi RC, Tao G, Scott B, Sapsford KE, Spindel S, Oh E, Jain 

V, Delehanty JB, Prasuhn DE, Boeneman K, Algar WR, Medintz IL. Reactive semiconductor 

nanocrystals for chemoselective biolabeling and multiplexed analysis. ACS Nano, 5(7):5579-93, 

July 26, 2011. 

Tock CL , Turner LR, Altiner A, Batra P, Booher SL, Coelho SG, Warner JA, Therrien JP, 

Turner ML, Miller SA, Beer JZ, Kraemer KH, Udey MC, Vogel JC, Terunuma A. Transcriptional 

signatures of full-spectrum and non-UVB-spectrum solar irradiation in human skin. Pigment Cell 

Melanoma Res. doi: 10.1111/j.1755-148X.2011.00899.x, August 17, 2011.

Oh E, Delehanty JB, Sapsford KE, Susumu K, Goswami R, Blanco-Canosa JB, Dawson PE, 

Granek J, Shoff M, Zhang Q, Goering PL, Huston A, Medintz IL. Cellular Uptake and Fate of 

PEGylated Gold Nanoparticles Is Dependent on Both Cell-Penetration Peptides and Particle Size. 

ACS Nano, 5(8):6434-48, August 23, 2011. 

Sapsford KE, Spindel S, Jennings T, Tao G, Triulzi RC, Algar WR, Medintz IL. Optimizing 

Two-Color Semiconductor Nanocrystal Immunoassays in Single Well Microtiter Plate Formats. 

Sensors, 11(8):7879-7891, 2011. 

Choi J, Reipa V, Hitchins VM, Goering PL, Malinauskas RA. Physicochemical characterization 

and in vitro hemolysis evaluation of silver nanoparticles. Toxicol Sci, 123(1):133-43, September 

2011. 

Doerge DR, Twaddle NC, Vanlandingham M, Brown RP, Fisher JW. Distribution of bisphenol A 

into tissues of adult, neonatal, and fetal Sprague-Dawley rats. Toxicol Appl Pharmacol, 

255(3):261-70, September 15, 2011. 

Coelho S, Ito S, Wakamatsu K, Miller S, Beer J, Hearing V. Distribution patterns of eumelanin 

and pheomelanin in human skin. Materials of the XXIst International Pigment Cell Conference, 

Bordeaux, France, September 21-24, 2011. 

Zhang Q, Hitchins VM, Schrand AM, Hussain SM, Goering PL. Uptake of gold nanoparticles in 

murine macrophage cells without cytotoxicity or production of pro-inflammatory mediators. 

Nanotoxicology, 5:284-95, September 2011. 

Godar DE. Worldwide increasing incidences of cutaneous malignant melanoma. J Skin Cancer, 

2011:858425, 2011. 

Austin CA, Umbreit TH, Brown KM, Barber DS, Dair BJ, Francke-Carroll S, Feswick A, SaintLouis MA, Hikawa H, Sieben KN, Goering PL. Distribution of silver nanoparticles in pregnant 

mice and developing embryos. Nanotoxicology, E-pub ahead of print, October 2011.

Godar DE, Pope SJ, Grant WB, Holick MF. Solar UV doses of adult Americans and vitamin D(3) 
52

production. Dermatoendocrinol, 3(4):243-50, October 2011. 

Lucas, AD Environmental fate of Polyhexamethylene biguanide, Bulletin of Environmental 

Contamination and Toxicology 88(3):322-325. DOI 10.1007/s00128-011-0436-3. October 2011

Tock CL, Turner LR, Altiner A, Batra P, Booher SL, Coelho SG, Warner JA, Therrien JP, Turner 

ML, Miller SA, Beer JZ, Kraemer KH, Udey MC, Vogel JC, Terunuma A. Transcriptional 

signatures of full-spectrum and non-UVB-spectrum solar irradiation in human skin. Pigment Cell 

Melanoma Res, 24(5):972-4, October 2011. 

Dobrovolsky VN, Elespuru RK, Bigger CA, Robison TW, Heflich RH. Monitoring humans for 

somatic mutation in the endogenous PIG-a gene using red blood cells. Environ Mol Mutagen, 

52(9):784-94, December 2011. 

Narayan R, Goering P. Laser micro- and nanofabrication of biomaterials. MRS Bull, 36(12):973-

82, December 2011.

Godar DE, Riskby, D'Orazio JA,. Naus N, Dion Paridaens D, de Klein A. Advances in Malignant 

Melanoma - Clinical and Research - InTech. Skin Pigmentation and Melanoma, Chapter 3. 

www.intechopen.com/books/advances-in-malignant-melanoma-clinical-and-researchperspectives

Division of Chemistry and Materials Science 

Saylor DM, Guyer JE, Wheeler D, Warren JA. Predicting microstructure development during 

casting of drug-eluting coatings. Acta Biomater, 7(2):604-13, February 2011. 

Forrey C, Yager KG, Broadaway SP. Molecular dynamics study of the role of the free surface on 

block copolymer thin film morphology and alignment. ACS Nano, 5(4):2895-907, April 26, 

2011. 

Sapsford KE, Tyner KM, Dair BJ, Deschamps JR, Medintz IL. Analyzing nanomaterial 

bioconjugates: a review of current and emerging purification and characterization techniques. 

Anal Chem, 83(12):4453-88, June 15, 2011. 

Davis EM, Benetatos NM, Regnault WF, Winey KI, Elabd YA. The influence of thermal history 

on structure and water transport in Parylene C coatings. Polymer, 52(23):5378-86, October 27, 

2011. 

Division of Electrical and Software Engineering 

Luo H, Chen J, Shi L, Mikailov M, Zhu H, Wang K, He L, Yang L. DRAR-CPI: a server for 

identifying drug repositioning potential and adverse drug reactions via the chemical-protein 

interactome. Nucleic Acids Res, 39(Suppl. 2):W492-W498, July 2011 . 

Zhang Y, Jetley R, Jones PL, Ray A. Generic safety requirements for developing safe insulin 

pump software. J Diabetes Sci Technol, 1;5(6):1403-19, November 2011.
53

Division of Imaging and Applied Mathematics 

Alam SK, Feleppa EJ, Rondeau M, Kalisz A, Garra BS. Ultrasonic multi-feature analysis 

procedure for computer-aided diagnosis of solid breast lesions. Ultrasonic Imaging, 33(1):17-38, 

January 2011. 

Armato SG, McLennan G, Bidaut L, McNitt-Gray MF, Meyer CR, Reeves AP, Zhao BS, Aberle 

DR, Henschke CI, Hoffman EA, Kazerooni EA, MacMahon H, van Beek EJR, Yankelevitz D, 

Biancardi AM, Bland PH, Brown MS, Engelmann RM, Laderach GE, Max D, Pais RC, Qing 

DPY, Roberts RY, Smith AR, Starkey A, Batra P, Caligiuri P, Farooqi A, Gladish GW, Jude CM, 

Munden RF, Petkovska I, Quint LE, Schwartz LH, Sundaram B, Dodd LE, Fenimore C, Gur D, 

Petrick N, Freymann J, Kirby J, Hughes B, Casteele AV, Gupte S, Sallam M, Heath MD, Kuhn 

MH, Dharaiya E, Burns R, Fryd DS, Salganicoff M, Anand V, Shreter U, Vastagh S, Croft BY, 

Clarke LP. The Lung Image Database Consortium, (LIDC) and Image Database Resource 

Initiative (IDRI): A Completed Reference Database of Lung Nodules on CT Scans. Medical

Physics, 38(2):915-31, February 2011. 

Doughty E, Kertesz-Farkas A, Bodenreider O, Thompson G, Adadey A, Peterson T, Kann MG. 

Toward an automatic method for extracting cancer- and other disease-related point mutations 

from the biomedical literature. Bioinformatics, 27(3):408-15, February 1, 2011. 

Freed M, de Zwart JA, Loud JT, El Khouli RH, Myers KJ, Greene MH, Duyn JH, Badano A. An 

anthropomorphic phantom for quantitative evaluation of breast MRI. Medical Physics, 38(2):743-

53, February 2011. 

Gavrielides MA, Gallas BD, Lenz P, Badano A, Hewitt SM. Observer variability in the 

interpretation of HER2/neu immunohistochemical expression with unaided and computer-aided 

digital microscopy. Arch Pathol Lab Med, 135(2):233-42, February 2011. 

Samuelson F, Gallas BD, Myers KJ, Petrick N, Pinsky P, Sahiner B, Campbell G, Pennello GA. 

The Importance of ROC Data. Academic Radiology, 18(2):257-8, February 2011. 

Badano A, Freed M, Fang YA. Oblique incidence effects in direct x-ray detectors: a first-order 

approximation using a physics-based analytical model. Medical Physics, 38(4):2095-8, April 

2011. 

Cho HC, Hadjiiski L, Sahiner B, Chan HP, Helvie M, Paramagul C, Nees AV. Similarity 

evaluation in a content-based image retrieval (CBIR) CADx system for characterization of breast 

masses on ultrasound images. Medical Physics, 38(4):1820-31, April 2011. 

Freed M, Park S, Badano A. A fast, angle-dependent, analytical model of CsI detector response 

for optimization of 3D x-ray breast imaging systems (vol 37, pg 2593, 2010). Medical Physics, 

38(4):2307, April 2011. 

Freed M, Badal A, Jennings RJ, Heras HD, Myers KJ, Badano A. X-ray properties of an 

anthropomorphic breast phantom for MRI and x-ray imaging. Phys Med Biol, 56(12):3513-33, 

May 23, 2011. 
54

Platisa L, Goossens B, Vansteenkiste E, Park S, Gallas BD, Badano A, Philips W. Channelized 

Hotelling observers for the assessment of volumetric imaging data sets. J Opt Soc Am A Opt 

Image Sci Vis, 28(6):1145-63, June 1, 2011. 

Samuelson FW. Two-sample models with monotonic likelihood ratios for ordinal regression. J 

Math Psychol, 55(3):223-8, June 2011. 

Sharma D, Fang Y, Zafar F, Karim KS, Badano A. Recombination models for spatio-temporal 

Monte Carlo transport of interacting carriers in semiconductors. Appl Phys Lett, 98(24):242111, 

June 13, 2011. 

Graff CG, Myers KJ. The ideal observer objective assessment metric for magnetic resonance 

imaging: application to signal detection tasks. Inf Process Med Imaging, 22:760-71, 2011. 

King R, Liu Y, Maruvada S, Herman B, Wear K, Harris G. Development and characterization of 

a tissue-mimicking material for high-intensity focused ultrasound. IEEE Trans Ultrason 

Ferroelectr, 58(7):1397-405, July 2011. 

Liu JM, Kabadi S, Van Uitert R, Petrick N, Deriche R, Summers RM. Improved computer-aided 

detection of small polyps in CT colonography using interpolation for curvature estimation. Med 

Phys, 38(7):4276-84, July 2011. 

Prince JL, Pham DL, Myers KJ. Editorial. Med Image Anal, 15(4):601-2, August 2011. 

Garra BS. Elastography: current status, future prospects, and making it work for you. Ultrasound 

Q, 27(3):177-86, September 2011. 

Zeng R, Petrick N, Gavrielides MA, Myers KJ. Approximations of noise covariance in multi-slice 

helical CT scans: impact on lung nodule size estimation. Phys Med Biol, 56(19):6223-42, 

September 6, 2011. 

Gu S, Gupta R, Kyprianou I. Computational high-resolution heart phantoms for medical imaging 

and dosimetry simulations. Phys Med Biol, 56(18):5845-64, September 21, 2011. 

Freed M, de Zwart JA, Hariharan P, R Myers M, Badano A. Development and characterization of 

a dynamic lesion phantom for the quantitative evaluation of dynamic contrast-enhanced MRI. 

Medical Physics, 38(10):5601-11, October 2011. 

Popescu LM. Nonparametric signal detectability evaluation using an exponential transformation 

of the FROC curve. Medical Physics, 38(10):5690-702, October 2011. 

Sarvazyan A, Hall TJ, Urban MW, Fatemi M, Aglyamov SR, Garra BS. An overview of 

elastography - an emerging branch of medical imaging. Curr Med Imaging Rev, 7(4):255-282, 

November 2011. 

Wear K, Gammell P, Maruvada S, Liu Y, Harris G. Time-delay spectrometry measurement of 

magnitude and phase of hydrophone response. IEEE Trans Ultrason Ferroelectr, 58(11):2325-33, 

November 2011. 

Freed M. Effect of protocol parameters on contrast agent washout curve separability in breast 

dynamic contrast enhanced MRI: A simulation study. Magn Reson Med, [Epub ahead of print], 
55

December 5, 2011. 

Division of Physics 

Strauss DG, Poole JE, Wagner GS, Selvester RH, Miller JM, Anderson J, Johnson G, McNulty 

SE, Mark DB, Lee KL, Bardy GH, Wu KC. An ECG index of myocardial scar enhances 

prediction of defibrillator shocks: an analysis of the Sudden Cardiac Death in Heart Failure Trial. 

Heart Rhythm, 8(1):38-45, January 2011. 

Tata DB, Waynant RW. Laser therapy: A review of its mechanism of action and potential 

medical applications. Laser Photon Rev, 5(1):1-12, January 2011. 

Kim DH, Song CG, Ilev IK, Kang JU. Axial-scanning low-coherence interferometer method for 

noncontact thickness measurement of biological samples. Applied Optics, 50(6):970-4, February 

20, 2011. 

Pantchenko OS, Seidman SJ, Guag JW, Witters DM Jr, Sponberg CL. Electromagnetic 

compatibility of implantable neurostimulators to RFID emitters. Biomed Eng Online, 10:50, June 

9, 2011. 

Soltysik DA, Thomasson D, Rajan S, Gonzalez-Castillo J, Dicamillo P, Biassou N. Headrepositioning does not reduce the reproducibility of fMRI activation in a block-design motor task. 

Neuroimage, 56(3):1329-37, June 1, 2011. 

Bachtel AD, Gray RA, Stohlman JM, Bourgeois EB, Pollard AE, Rogers JM. A Novel Approach 

to Dual Excitation Ratiometric Optical Mapping of Cardiac Action Potentials With Di-4-

ANEPPS Using Pulsed LED Excitation. IEEE Transactions in Biomedical Engineering, 

58(7):2120-6, July 2011. 

Gray RA, Wikswo JP. Cardiovascular disease: several small shocks beat one big one. Nature, 

475(7355):181-2, July 14, 2011. 

Umberger K, Bassen HI. Radiated radiofrequency immunity testing of automated external 

defibrillators - modifications of applicable standards are needed. Biomedical Engineering Online, 

10:66, July 29, 2011. 

Wang MS, Lin L, Chen J, Jackson D, Kainz W, Qi YH, Jarmuszewski P. Evaluation and 

Optimization of the Specific Absorption Rate for Multiantenna Systems. IEEE Trans 

Electromagn C, 53(3):628-37, August 2011. 

Engblom H, Strauss DG, Heden B, Hedström E, Jovinge S, Götberg M, Erlinge D, Wagner GS, 

Arheden H. The evaluation of an electrocardiographic myocardial ischemia acuteness score to

predict the amount of myocardial salvage achieved by early percutaneous coronary intervention 

Clinical validation with myocardial perfusion single photon emission computed tomography and 

cardiac magnetic resonance. Journal of Electrocardiology, 44(5):525-32, September-October 

2011. 

Kim DH, Shi D, Ilev IK. Alternative method for measuring effective focal length of lenses using 

the front and back surface reflections from a reference plate. Applied Optics, 50(26):5163-8, 
56

September 10, 2011. 

Loring Z, Chelliah S, Selvester RH, Wagner G, Strauss DG. A detailed guide for quantification of 

myocardial scar with the Selvester QRS score in the presence of electrocardiogram confounders. 

Journal of Electrocardiology, 44(5):544-54, September-October 2011. 

Abliz E, Collins JE, Bell H, Tata DB. Novel applications of diagnostic X-rays in activating a 

clinical photodynamic drug: Photofrin II through X-ray induced visible luminescence from "rareearth" formulated particles. J Xray Sci Technol, 9(4):521-30, 2011. 

Cohen E, Agrawal A, Connors M, Hansen B, Charkhkar H, Pfefer J. Optical coherence 

tomography imaging of retinal damage in real time under a stimulus electrode. J Neural Eng, 

8(5):056017, October 2011. 

Seidman S, Kainz W, Ruggera P, Mendoza G. Wireless Coexistence and EMC of Bluetooth and 

802.11b Devices in Controlled Laboratory Settings. Open Biomed Eng J, 5:74-82, 2011. 

Pfefer TJ, Wang Q, Drezek RA. Monte Carlo modeling of time-resolved fluorescence for depthselective interrogation of layered tissue. Comput Methods Programs Biomed, 104(2):161-7, 

November 2011. 

Witters D. Wireless medical systems: risks, challenges, and opportunities. Biomed Instrum 

Technol, 2011 Fall;Suppl:49-52, 2011. 

Huang Y, Zhang K, Kang JU, Calogero D, James RH, Ilev IK. Noncontact common-path Fourier 

domain optical coherence tomography method for in vitro intraocular lens power measurement. J 

Biomed Opt, 16(12):126005, December 2011. 

Kim DH. Using a melanin granule lattice model to study the thermal effects of pulsed and 

scanning light irradiations through a measurement aperture. J Biomed Opt, 16(12):125002, 

December 2011. 

Kim DH, James RH, Landry RJ, Calogero D, Anderson J, Ilev IK. Quantification of glistenings in 

intraocular lenses using a ballistic-photon removing integrating-sphere method. Applied Optics,

50(35):6461-7, December 10, 2011. 

Division of Solid and Fluid Mechanics 

Aguel F, Hillebrenner M, Stewart SFC, Swain J, Hampshire V, Zuckerman B. U.S. regulatory 

considerations for heart valves implanted by minimally invasive surgery. Cardiovasc Eng 

Tech.;2:62-65, 2011.

Dasgupta S, Banerjee RK, Hariharan P, Myers MR. Beam localization in HIFU temperature 

measurements using thermocouples, with application to cooling by large blood vessels. 

Ultrasonics, 51(2):171-80, Feburary 2011. 

Bigelow TA, Church CC, Sandstrom K, Abbott JG, Ziskin MC, Edmonds PD, Herman B, 

Thomenius KE, Teo TJ. The thermal index: its strengths, weaknesses, and proposed 
57

improvements. J Ultrasound Med, 30(5):714-34, May 2011. 

Dasgupta S, Banerjee RK, Hariharan P, Myers MR. Beam localization in HIFU temperature 

measurements using thermocouples, with application to cooling by large blood vessels. 

Ultrasonics, 51(2):171-80, Feburary 2011. 

Dasgupta S, Das P, Wansapura J, Hariharan P, Pratt R, Witte D, Myers MR, Banerjee RK, 

Reduction of noise from MR thermometry measurements during HIFU characterization 

procedures. Journal of Nanotechnology in Engineering and Medicine, 2:(2), May 2011.

Lu Q, Malinauskas RA. Comparison of two platelet activation markers using flow cytometry after 

in vitro shear stress exposure of whole human blood. Artif Organs,;35(2):137-44, February 

2011. 

Guerraty MA, Grant GR, Karanian JW, Chiesa OA, Pritchard WF, Davies PF. Side-specific 

expression of activated leukocyte adhesion molecule (ALCAM; CD166) in pathosusceptible 

regions of swine aortic valve endothelium. J Heart Valve Dis, 20(2):165-7, March 2011. 

Hariharan P, Giarra M, Reddy V, Day SW, Manning KB, Deutsch S, Stewart SF, Myers MR, 

Berman MR, Burgreen GW, Paterson EG, Malinauskas RA. Multilaboratory particle image 

velocimetry analysis of the FDA benchmark nozzle model to support validation of computational 

fluid dynamics simulations. J Biomech Eng, 133(4):041002, April 2011. 

Harris GR, Herman BA, Myers MR. A comparison of the thermal-dose equation and the 

intensity-time product, Itm, for predicting tissue damage thresholds. Ultrasound Med Biol, 

37(4):580-6, April 2011.

Maruvada S, Liu Y, Herman BA, Harris GR. Evaluation of a tissue mimicking material during 

HIFU exposure. Journal of Physics: Conference Series, vol. 279, 012010, 2011.

Myers MR, Giridhar D. Theoretical framework for quantitatively estimating ultrasound beam 

intensities using infrared thermography. J Acoust Soc Am, 129(6):4073-83, June 2011. 

King R, Liu Y, Maruvada S, Herman B, Wear K, Harris G. Development and characterization of 

a tissue-mimicking material for high-intensity focused ultrasound. IEEE Trans Ultrason 

Ferroelectr, 58(7):1397-405, July 2011. 

Choi J, Reipa V, Hitchins VM, Goering PL, Malinauskas RA. Physicochemical characterization 

and in vitro hemolysis evaluation of silver nanoparticles. Toxicol Sci, 123(1):133-43, September 

2011. 

Maruvada S, Liu Y, Pritchard WF, Herman BA, Harris GR. Comparative study of temperature 

measurements in ex vivo swine muscle and a tissue-mimicking material during high intensity 

focused ultrasound exposures. Phys Med Biol, 57(1):1-19, November 2011. 
58

APPENDIX B – OSEL Presentations 

January 1, 2011 – December 31, 2011 (ordered by date) 

Division of Biology

Tyner KM, Wokovich AM, Godar DE, Doub WH, Sadrieh N. The state of nano-sized titanium 

dioxide (TiO2) may affect sunscreen performance. Int J Cosmet Sci. 2011 Jun;33(3):234-44. doi: 

10.1111/j.1468-2494.2010.00622.x. Epub 2011 January 25, 2011.

Fisher B. General principles and study designs for reproductive and developmental toxicology 

studies in small molecules; outcome, analysis, interpretation, and assessment (Seg 1, 2, and 3). 

Reproductive Toxicity (CDER Training Course), Silver Spring, MD, March 3, 2011.

Brown R. Categorization of compounds released from medical device materials into Cramer 

Classes using Toxtree software. Society of Toxicology 50th Annual Meeting, Washington, DC, 

March 6-10, 2011.

Brown RP, Hutchinson RW. Biodegradable materials for tissue engineering: applications and 

safety assessment. Society of Toxicology 50th Annual Meeting, Washington, DC, March 6-10, 

2011.

Brown RP, Zhang Q, Barber DS, Komiyama AC, Goering PL. Plasma, urine, and tissue 

concentrations of hexavalent chromium associated acute kidney injury in Sprague Dawley rats. 

Society of Toxicology 50th Annual Meeting, Washington, DC, March 6-10, 2011.

Freeman A, Komiyarna A, Fazio J, Hamilla S, Dinesdurage H, Brown RP. Evaluation of the 

sensitivity of endpoints in the ISO 10993-11 systemic toxicity standard using positive control 

compounds. Society of Toxicology 50th Annual Meeting, Washington, DC, March 6-10, 2011.

Goering P. Opportunities for research and training in a federal regulatory agency. Society of 

Toxicology 50th Annual Meeting, Washington, DC, March 6-10, 2011.

Hoffmann D, Krishnamoorthy A, Ramirez Gonzalez V, Zhang Q, Goering PL, Brown RB, 

Waikar S, Vaidya VS. Urinary fibrinogen: A mechanistic translational biomarker for vascular 

dysfunction and inflammation in the kidney. Society of Toxicology 50th Annual Meeting, 

Washington, DC, March 6-10, 2011.

Hutchinson RW, Brown R, Cheeseman MA, Cammack J. The application of the threshold of 

toxicological concern concept to the preclinical safety assessment of non-pharmaceutical medical 

products, including medical devices and combination drug-device products. Society of 

Toxicology 50th Annual Meeting, Washington, DC, March 6-10, 2011.

Kulkarni P, Dinesdurage H, Brown RP. Rapid toxicity screening of polymeric materials using the 

Microtox Assay. Society of Toxicology 50th Annual Meeting, Washington, DC, March 6-10, 

2011.
59

Zhang Q, Gamboa da Costa G, Beger R, Schnackenberg L, Sun J, Pence L, Bhattacharyya S, 

Jacob C, Brown RP, Goering PL. Urinary biomarker detection of melamine-cyanuric acidinduced kidney damage in rats. Society of Toxicology 50th Annual Meeting, Washington, DC, 

March 6-10, 2011.

Bagley B, Kulkarni P, Kueshner N, Brown R, Moilanen L. In silico mutagenicity prediction for 

leachable components of dental devices. Society of Toxicology Annual Meeting, March 15, 

2011. 

Betz M. My career as a bioengineer. Century High School Career Fair, Sykesville, MD, March 

18, 2011.

Breger J, Fisher B, Isayeva I, Wang N. Encapsulation of islets in 'click' crosslinked alginate 

capsules and response to glucose challenge. Graduate Research Interaction Day, College Park, 

MD, April 6-6, 2011.

Breger J. Design of click hydrogels for cell encapsulation. Joyce Breger's Dissertation Defense, 

College Park, MD, April 8, 2011.

Wang NS, Breger J. Design of Click hydrogels for cell encapsulation (dissertation defense), April 

18, 2011. 

Goering P. Comparison of cytotoxic and inflammatory responses of silicone nano- and

microparticles, and gold nanoparticles, in RAW 264.7 macrophages. Toxicology and Risk 

Assessment Conference 2011, Cincinnati, OH, April 25-27, 2011.

Shoff ME, Hitchins V. Important variables when using Acanthamoeba to evaluate contact lens 

solutions. Association for Research in Vision and Ophthalmology 2011 Annual Meeting, Ft. 

Lauderdale, FL, May 1-5, 2011.

Tu E, Shoff M, Joslin C. The addition of benzalkonium chloride to Moxifloxacin confers antiacanthamoebal activity in an in vitro model. Association for Research in Vision and 

Ophthalmology 2011 Annual Meeting, Ft. Lauderdale, FL, May 1-5, 2011.

Clavet C, Lucas A, Chaput M, Gonzalez J, Hitchins V. Effects of contact lens, lens cases and 

“soil” on disinfection activity in multipurpose contact lens solution against Fusarium solani. 

American Society for Microbiology, 111th General Meeting, New Orleans, LA, May 21-24, 

2011.

Lucas A. Environmental fate of Polyhexamethalene Biguannide. American Chemical Society, 5th 

Mid Atlantic Regional Meeting, College Park, MD, May 21-24, 2011.

Mu Y, Keene A, Weaver J, Fisher B. Development of a clinically relevant assay using dendritic 

cell surface markesr to predict human allergic potential of medical device materials. CYTO 2011, 

Baltimore, MD, May 21-25, 2011.

Haugen S, Hitchins, V. A method to quantitatively assess residual solid soils in reusable medical 

devices. Reprocessing of Reusable Medical Devices, Silver Spring, MD, June 9, 2011.

Goering PL. What we know and don't know about the bioeffects of nanomaterials: challenges in 

developing experimental approaches for safety assessment. CFSAN MOD Seminar Series I, 
60

Beltsville, MD, June 16, 2011.

Yang XC. Elicitation of noninferiority margin. Joint Statistical Meetings 2011, Miami Beach, FL, 

July 30 - August 4, 2011.

Brown R, Kuldami P, Gordon E. Advancing computational toxicology modeling in the Center for 

Devices and Radiological Health. Workshop on Computer Methods for Medical Devices,

September 9, 2011. 

Kulkami P, Brown R.Validation of Toxtree software for predicting the carcinogencity of 

compounds released from medical device materials. Workshop on Computer Methods for 

Medical Devices, September 9, 2011. 

Elespuru R. Genotoxicity assessment of nanomaterials: Update. Genetic Toxicology Association, 

September 14, 2011. 

Rajani A. Miniaturization of a Salmonella typhimurium genotoxicity assay. Genetic Toxicology 

Association, September 15, 2011.

Coelho S, Ito S, Wakamatsu K, Miller S, Beer J, Hearing V. Distribution patterns of eumelanin 

and pheomelanin in human skin. International Pigment Cell Conference XXIst, Bordeaux, 

France, September 21-24, 2011.

Elespuru R. Analysis of the relative contribution of genetic, developmental and environmental 

causes to the origin of birth defects. International Congress of Human Genetics, 12th, Montreal, 

Canada, October 11-15, 2011.

Breger J, Fisher B, Isayeva I, Baeva L, Wang N. Optimization of the 'click' reaction for 

therapeutic cell encapsulation utilizing RIN-5F cells. Biomedical Engineering Society 2011 

Annual Meeting, Hartford, CT, October 12-15, 2011.

Hitchins V. FDA’s perspective of “clean” for reprocessing medical devices. Association for the 

Advancement of Medical Instrumentation and FDA, AAMI/FDA Medical Device Reprocessing 

Summit, October 12, 2011. 

Choi J, Reipa V, Hitchins V, Goering P, Malinauskas R. Human blood biocompatibility of silver 

nanoparticles. AIChE (American Institute of Chemical Engineers), Annual Meeting of Chemical 

Engineers, October 16, 2011. 

Brown R. The basic elements of biocompatibility studies. FDA, Basic Nonclinical Bioresearch 

Monitoring, October 17, 2011. 

Elespuru RK, Rajani A. Evolution of colon cancer is reflected in DNA mutational sequence 

profiles. Environmental Mutagen Society 42nd Annual Meeting, Montreal, Canada, October 15-

19, 2011.

Elespuru RK, Rajani A. Miniaturization of a Salmonella Typhimurium genotoxicity assay. 

Environmental Mutagen Society 42nd Annual Meeting, Montreal, Canada, October 15-19, 2011. 

Fisher B. (Developmental) toxicity testing in the 21st century: Leveraging for alternative models.
61

Middle Atlantic Reproductive and Teragology Association (MARTA), 2011 MARTA Meeting, 

October 20, 2011. 

Brown R. Biological effects of cobalt and chromium released from CoCr alloy: Research 

activities in the CDRH/OSEL Laboratory of Toxicology and Biocompatibility, National Institute 

of Standards and Technology, Failure of Metal-on-Metal Hip Implants Meeting, November 17, 

2011. 

Wood S. Development of anti-Ebola MHC tetramers as a surrogate marker to evaluate cellmediated immunity in vaccines:a computational approach, NIAID Research update, November 

21, 2011. 

Division of Chemistry and Materials Science

Guo J, Cho S, Luu HD. Determination of Bisphenol-A Compounds Leachable from 

Polycarbonate- and Polysulfone-based Hemodialyzers. Society of Toxicology 50th Annual 

Meeting, Washington, DC, March 6-10, 2011.

Berger J, Fisher B, Isayeva I, Wang N. Encapsulation of Islets In 'Click' Crosslinked Alginate 

Capsules and Response to Glucose Challenge. Graduate Research Interaction Day, College Park, 

MD, April 6-6, 2011.

Patwardhan DV. Biomaterials- A FDA Perspective. Society for Biomaterials Annual Meeting and 

Exposition 2011, Orlando, FL, April 13-16, 2011.

Guo J, Saylor DM, Patwardan DV. The Impact of Sex-Based Differences in atherosclerotic 

Plaque on Drug Release from Drug Eluting Stents (DES). Controlled Release Society 38th 

Annual Meeting and Exposition, National Harbor, MD, July 30-August 3, 2011.

McDermott MK. Nitroxide antioxidants for the prevention of oxidation in crosslinked ultra-high 

molecular weight polyethylene. Implant Research Center, 5th UHMWPE International Meeting, 

September 22, 2011. 

Breger J, Fisher B, Isayeva I, Baeva L, Wang N. Optimization of the 'Click' Reaction for 

Therapeutic Cell Encapsulation Utilizing RIN-5F Cells. Biomedical Engineering Society 2011 

Annual Meeting, Hartford, CT, October 12-15, 2011.

Takmakov P. In-vitro system to investigate causes of long-term implant failure. USUHS, 

Neuroscience Program Poster Session, December 1, 2011. 

Division of Electrical and Software Engineering

Fitzgerald B. Utility of shareable distributed mega-computing platform for storing, managing, and 

analyzing extreme-scale observational data. DIA/FDA CDER/CBER Computational Science 

Annual Meeting 2011, Arlington, VA, March 14-15, 2011.
62

Sudarsan SD. Signal detection using text mining in large document repositories. George Mason 

University Department of Computer Science Grand Seminar, Fairfax, VA, April 12, 2011.

Silberberg J. Electromagnetic compatibility (APEMC 2011), edition 4 of IEC 60601-1-2. The 

Korean Institute of Electromagnetic Engineering and The Korean Institute of Electromagnetic 

Engineering and Science (KIEES), 2011 Asia-Pacific Symposium & Exhibition, May 18, 2011. 

Ganesan D, Lindvall M, Cleaveland R, Jetley R, Jones P, Zhang Y. Generic safety requirements 

for developing safe insulin pump software. IEEE/IFIP Conference on Software Architecture 9, 

Boulder, CO, June 20-24, 2011.

Silberberg J. Edition 4 of IEC 60601-1-2, Japan Society of Medical and Biological Engineering, 

Study group for Medical and Welfare EMC, the 2nd meeting, September 3, 2011. 

Silberberg J. Edition 4 of IEC 60601-1-2 (Medical electrical equipment ), Swedish Society for 

Medical Engineering and Physics, Medicinteknikdagarna Conference, October 11, 2011. 

Jones PL. AAMI, Safety Assurance Cases for Medical Devices, Thoughts on assurance cases, 

October 29, 2011. 

Division of Imaging and Applied Mathematics

Abboud S, Lee K, Vinehout K, Paquerault S, Kyprianou IS. A comparison of methods for 

estimating the line spread function of a CT imaging system. Medical Imaging 2011, Lake Buena 

Vista, FL, February 12-17, 2011.

Brunner CC, Renger B, Hoeschen C, Kyprianou IS. Investigation of a method to estimate the 

MTF and NPS of CT towards creating an international standard. Medical Imaging 2011, Lake 

Buena Vista, FL, February 12-17, 2011.

Chen W, Petrick N, Sahiner B. Assessment of updated CAD without a new reader study: effect of 

calibration of computer output on the computer-aided reader performance in CADx. Medical 

Imaging 2011, Lake Buena Vista, FL, February 12-17, 2011.

Paquerault S, Yarusso LM, Sahiner B, Kettermann A, Hadjiiski LM, Chan HP. Analysis of the 

number of distinct findings obtained by multiple readers in an MRMC study: When do findings 

obtained from the addition of new readers become redundant, or otherwise negligible?. Medical 

Imaging 2011, Lake Buena Vista, FL, February 12-17, 2011.

Petrick N, Zeng R, Gavrielides MA, Kim HJG McNitt-Gray MF, Clunie D, Borradaile K, Ford R, 

Fenimore C, Lu ZQJ, Zhao B, Buckler AJ. Evaluation of 1D, 2D and 3D nodule size estimation 

by radiologists for spherical and non-spherical nodules through CT thoracic phantom imaging. 

Medical Imaging 2011, Lake Buena Vista, FL, February 12-17, 2011.

Rupcich F, Schmidt TG, Kyprianou I, Badal A. Energy deposition in the breast during CT 

scanning: quantification and implications for dose reduction. Medical Imaging 2011, Lake Buena 

Vista, FL, February 12-17, 2011.
63

Sahiner B, Petrick N, Paquerault S, Chen W, Nguyen T. Agreement between two versions of a 

CADx system: a simulation study. Medical Imaging 2011, Lake Buena Vista, FL, February 12-

17, 2011.

Wang S, Summers RM, Petrick N, Van Uitert RL, Periaswamy S. 3D supine and prone colon 

registration for computed tomographic colonography scans based on graph matching. Medical 

Imaging 2011, Lake Buena Vista, FL, February 12-17, 2011.

Zeng R, Myers KJ. Task-based comparative study of iterative image reconstruction methods for 

limited-angle x-ray tomography. Medical Imaging 2011, Lake Buena Vista, FL, February 12-17, 

2011.

Wear KA, Maruvada S, Gammell PM, Liu Y, Harris GR. Comparison of hydrophone phase 

response obtained via time domain spectroscopy measurement and Hilbert Transformation. 

Therapeutic Ultrasound, 11th International Symposium on, New York, NY, April 11-13, 2011.

Wear KA. Improvements in measurements of BUA and SOS in human calcaneus. International 

Symposium on Ultrasonic Imaging and Tissue Characterization, Wear KA, June 13, 2011. 

Sharma D, Badal A, Fang Y, Badano A. HybridMANTIS: a novel method for faster Monte Carlo 

simulation of x-ray imaging detectors. American Association of Physicists in Medicine 2011, 

July 1, 2011. 

Chen W. A Semi-parametric Roc approach to assessing biomarkers subject to a measurement 

error and limit of detection. Joint Statistical Meetings 2011, Miami Beach, FL, July 30-August 4, 

2011.

Samuelson F, Brown D. Application of Cover’s Theorem to the evaluation of the performance of 

CI observers. International Neural Network Society and Institute of Electrical and Electronics 

Engineers Computational Intelligence Society, 2011 International Joint Conference on Neural 

Networks, July 31, 2011. 

Sechopoulos I, Abboud S, Ali E, Badal A, Badano A, Feng SSJ, Kyprianou I, McNitt-Gray M, 

Samei E, Turner A. Introduction to the AAPM Task Group No. 195 - Monte Carlo reference data 

sets for imaging research. American Association for Physicists in Medicine 2011 Annual 

Meeting, Vancouver, Canada, July 31-August 4, 2011.

Sharma D, Badal A, Fang Y, Badano A. Hybridmantis: A novel method for faster Monte Carlo 

simulation of X-ray imaging detectors. American Association for Physicists in Medicine 2011 

Annual Meeting, Vancouver, Canada, July 31-August 4, 2011.

Badal A, Badano A. Fast and accurate estimation of organ doses in medical imaging using a 

GPU-accelerated Monte Carlo Simulation Code. American Association for Physicists in 

Medicine 2011 Annual Meeting, Vancouver, Canada, July 31-August 4, 2011.

Badano A, Kumcu A, Platisa L, Platisa M, Vansteenkiste E, Deblaere K, Philips W. Trends in 

reader behavior for a signal detection task in multi- and single-slice volumetric images. Medical 

Image Perception Society XIV Conference, Dublin, Ireland, August 9-12, 2011.

Gallas B, Gavrielides M. Reader studies of concordance, a generalized AUC. Medical Image 

Perception Conference, August 9, 2011. 
64

Gallas BD, Badano A, Platisa L, Kumcu A, Platisa M, Vnsteenkiste E, Deblaere K, Philips W. 

Model and human observer studies in volumetric images for detection tasks with varying 

complexity. Medical Imaging 2011, Dublin, Ireland, August 9-12, 2011.

Gu S, Badal-Soler A, Kyprianou I. Digital high-resolution heart phantom. Validation of 

Computer Methods for Medical Devices, Silver Spring, MD, September 7-9, 2011.

Platisa L, Marchessoux C, Kimpe T, Vansteenkiste E, Philipsa W. Channelized hotelling 

observers for signal detection in stack-mode reading of volumetric images. ICIP 2011, 

September 14, 2011. 

Gallas BD, Pinsky P. Enriched designs for assessing predictive performance – analysis of bias 

and variance. FDA/Industry Statistics Workshop 2011, Washington, DC, September 19-21, 

2011.

Sze C, Shama D, Vivek, Badano A. Depth-of-interaction estimates in a micro-columnar 

scintillator structure from optical transport Monte Carlo MANTIS simulations. IEEE, Institute of 

Electrical and Electronics Engineers, Nuclear Science Symposium and Medical Imaging 

Conference 2011, October 23, 2011. 

Sahiner B. Computer-assisted decision systems in radiology – the hope, the hype and the hard 

truth: Applications II: Emerging applications, Radiological Society of North America 2011, 

November 26, 2011. 

Cho H, Hadjiiski L, Sahiner B, Chan H, Paramugal C, Helvie M, Nees A. Interactive contentbased image retrieval (CBIR) computer-aided diagnosis (CADx) system for ultrasound breast 

masses using relevance feedback. Radiological Society of North America 2011, November 26, 

2011. 

Petrick N. Challenges in breast imaging - evaluation of current and emerging technologies in 

breast imaging, Radiological Society of North America 2011 Refresher Course, 

November 27, 2011. 

Garra BS, DeStigter KK, Lawton K, Rielly M, Noordvyk A. Computerized reporting & outcomes 

tracking of remotely reported examinations in a low resourced rural environment: requirements 

and practical solutions, Radiological Society of North American 2011, November 27, 2011. 

Gavrielides M, Zeng R, Sahiner B, Myers K, Petrick N. Effect of overlapping reconstruction on 

lung nodule volume estimation with multi-detector CT. RSNA 2011, Chicago, IL, November 27-

27, 2011.

Petrick N, Linguraru MG, Sandberg J, Summers RM. Hepatic volumetric nomograms from 

automated analysis of abdominal CT. RSNA 2011, Chicago, IL, November 27 - December 2, 

2011.

Rupich F, Kyprianou I, Badal A, Gilat T. A technique for comparing CT acquisition methods 

[intended to reduce patient dose] with respect to breast dose and a task-based image quality 

metric. RSNA 2011, Chicago, IL, November 27-27, 2011.
65

Zbijeqski W, Badal-Soler A, Kyprianou I, Siewerdsen JH. Scatter properties of compact 

geometry cone-beam CT systems. RSNA 2011, Chicago, IL, November 27-27, 2011.

Division of Physics

Agrawal A, Connors M, Pfefer J, Chang R, Stafford C, Hwang J. System-independent assessment 

of OCT axial resolution with a "bar chart" phantom. SPIE Photonics West 2011, San Francisco, 

CA, January 22-27, 2011.

Kim DH, Ilev IK, Han YG. A thickness measurement method for biological samples using 

lensed-fiber sensors. SPIE Photonics West 2011, San Francisco, CA, January 22-27, 2011.

Wang Q, Pfefer J, Le D, Ramella-Roman J. Broadband UV-Vis optical property measurement in 

layered turbid media. SPIE Photonics West 2011, San Francisco, CA, January 22-27, 2011.

Witters D. Considerations for RFID and wireless technology in healthcare. RFID & RTLS in 

Healthcare Symposium, Orlando, FL, February 20, 2011.

Strauss DG. Novel ECG-MRI methods to improve patient selection for ICDs. Magnetic and 

Electrical Technologies Meeting, Maastricht, Netherlands, February 24-25, 2011.

Ilev IK. Advanced multifunctional imaging and sensing approaches in biophotonics and 

nanobiophotonics. George Washington University Seminar, Washington, DC, March 4, 2011.

Witters D. Safety and effectiveness for wireless technology in healthcare. Symposium on Medical 

Information and Communications Technology 2011, Yokohama City, Japan, March 4, 2011.

Kainz W. RF hotspots in multi transmit RF MR coils. Thermal Workshop on RF Hotspots, 

Zurich, Switzerland, March 21-22, 2011.

Johnson LJ, Cohen E, Ilg D, Klein R, Skeath P, Scribner DA. A novel 81,000 electrode spike 

recording array using a trans-impedance amplifier-based imaging chip. Dr. Jack Judy, DARPA 

BAA, April 8, 2011. 

Cohen E. Quantitative measurement of retinal damage in real-time under a stimulus electrode 

using OCT, University of Maryland, Metropolitan Biophotonics Symposium 2011, April 15, 

2011. 

Le D, Wang Q, Ramella-Roman J, Pfefer J. Evaluation of a fiber-optic system for broadband UVVis optical property measurement in layered tissue. Metropolitan Biophotonics Symposium, 3rd 

Annual, University of Maryland, College Park, MD, April 16, 2011.

Aloraefy M, Sapsford K, Roman JR, Pfefer J. Implementation and validation of a FRET-based 

biosensor for continuous glucose sensing. Metropolitan Biophotonics Symposium 2011, College 

Park, MD, April 16, 2011.

Ilev IK. All-in-one imaging and sensing approaches in biophotonics. University of Maryland, 

College Park, (Invited talk at Metropolitan Biophotonics Symposium 2011), April 16, 2011. 
66

Cohen E, Agrawal A, Pfefer JT, Connors M, Hansen B, Charkhkar H. OCT imaging of retinal 

damage in real-time under a stimulus electrode. Association for Research in Vision and 

Ophthalmology, ARVO 2011, May 1, 2011. 

Cohen E. OCT imaging of retinal damage in real-time under a stimulus electrode. NEI/FDA, 

2011 NEI/FDA Endpoints Symposium, May 6, 2011. 

Pantchenko O. To develop a method for testing electromagnetic compatibility between 

implantable neurostimulators and low frequency radio frequency identification emitters. 

Advancement to Candidacy Examination, Santa Cruz, CA, May 16-16, 2011.

Chou CK, Angelone LM, Guy AW. Electrically conductive objects in contact with biological 

tissues during RF exposure. Bioelectromagnetics Society 33rd Annual Meeting, Nova Scotia, 

Canada, June 12-17, 2011.

Witters D. A roundtable discussion: issues and challenges in it network management. 

Association for the Advancement of Medical Instrumentation Meeting 2011, June 15-15, 2011.

Soltysik D, Thomasson D, Rajan S, Gonzalez-Castillo J, DiCamillo P. Head-repositioning does 

not reduce the reproducibility of block-design motor fMRI activation. Human Brain Mapping 

2011, Quebec City, Canada, June 26-30, 2011.

Strauss D. Novel methods to improve patient selection for ICDs and CRT. Karolinska University 

Hospital, ,August 11, 2011. 

Gray R. Cardiovascular device development and collaborations. University of Virginia-FDA 

Medical Device Technology Innovation Partnerships, September 26, 2011. 

Woolsey N, Ilev I, Calhoun W. Characterizing light polarization effects through corneal tissue 

using lasers. Biomedical Engineering Society 2011 Annual Meeting, Hartford, CT, October 12-

15, 2011.

Mewton N, Strauss DG, Liu CY, Marchlinsky FE, Tereshchenko L, Killian T, Cox C, Verrier RL, 

Nearing B, Rizzi P, Wu KC, Spooner P, Lim JAC. Myocardial scar and fibrosis in patients at risk 

for sudden cardiac death as defined by 12-lead ECG QRS score and QRS-T angle. American 

Heart Association Scientific Sessions 2011, Orlando, FL, November 12, 2011.

Strauss D, Mewton N, Verrier R, Nearing B, Killian T, Marchlinsky F, Tereschenko L, Cox C, 

Spooner P. Screening entire health system ECG databases to identify patients with abnormal 

myocardial substrate at potential increased risk for arrhythmic death. American Heart 

Association, AHA Scientific Sessions 2011, November 12, 2011. 

Strauss DG, Selvester RH, Wagner GS, Loring Z, Gerstenblith G, Weiss RG, Wu KC. Scar size 

and etiology of right vs. left bundle branch block: insights from cardiac magnetic resonance and 

alcohol septal ablation. American Heart Association Scientific Sessions 2011, Orlando, FL, 

November 12, 2011.

Division of Solid and Fluid Mechanics 
67

Herbertson L. Medical Devices Regulations, Penn State University, March 3, 2011. 

Stewart, Hariharan, Paterson, Burgreen, Reddy, Day, Giarra, Manning, Deutsch, Myers, Berman, 

Malinauskas. Results of the FDA interlaboratory computational study in a nozzle with a sudden 

contraction and conical diffuser. 2nd International Conference on Computational and 

Mathematical Biomedical Engineering – CMBE2011, Fairfax, VA, March 30-April 21, 2011. 

(Extended abstract published in 2nd International Conference on Computational & Mathematical 

Biomedical Engineering (2011), P. Nithiarasu and R. Löhner (eds), Swansea University, UK, pp. 

391-394).

Liu Y, Maruvada S, Herman BA, Harris GR. Temperature-dependent physical properties of a 

HIFU blood-mimicking fluid, 11th International Symposium on Therapeutic Ultrasound, April 1, 

2011. 

Di Prima Ma. Material and Design Considerations for Orthopedic Devices. University of Texas at 

Dallas Department of Mechanical Engineering, Seminar, April 4, 2011. 

Soneson JE. Practical limits of the parabolic approximation for focused ultrasound beams. 

International Symposium on Therapeutic Ultrasound 2011, April 11, 2011. 

Liu Y, Maruvada S, Herman B, Harris G. Temperature-dependent physical properties of egg 

white for HIFU applications. Therapeutic Ultrasound, 11th International Symposium on, New 

York, NY, April 11-13, 2011.

Myers M, Giridhar D. Quantitative transducer characterization using infrared thermography. 

therapeutic ultrasound, 11th International Symposium on, New York, NY, April 11-13, 2011.

Vesnovsky O., Farrokh B, Topoleski LDT, Grossman LW. The Influence of machining on microhardness properties of CoCrMo alloys. Transactions of the Society for Biomaterials, April 13, 

2011. 

Wear KA, Maruvada S, Gammell PM, Liu Y, Harris GR.Time domain spectrometry for 

measurement of the hydrophone phase response. 55th Annual Convention of the American 

Institute of Ultrasound in Medicine, New York, NY, April 2011.

Maruvada S, Liu Y, Herman BA, Harris GR. Evaluation of a tissue-mimicking material during

HIFU exposure. Advanced Metrology for Ultrasound in Medicine conference, May 12, 2011. 

Hariharan P, Giridhar D, Robinson RA, Myers MR. Techniques for performing quantitative 

measurements of HIFU intensity distributions noninvasively. Acoustical Society of America, 

161st meeting, May 23, 2011. 

Duraiswamy N, Weaver JD, Retta SM, Stewart SFC, Wu C. Evaluating soft tissue leaflet stresses 

in non-circularly deployed heart valves. ASAIO Annual Conference, Washington, DC, June 10, 

2011.

Herbertson, Kameneva, Olia, Daly, Smith, Noatch, Malinauskas. Interlaboratory study of flowinduced hemolysis using the FDA benchmark nozzle model. ASAIO annual conference, 

Washington, DC. Abstract: ASAIO J, 57(2):95, June 10-12, 2011.
68

Lu, Chiang, Malinauskas. Presentation at ASAIO (by Q. Lu). Anticoagulation of blood from 

different species for potential use in in vitro thrombosis tests of medical devices. ASAIO annual 

conference, Washington, DC., Abstract: ASAIO J, 57(2):111, June 10-12, 2011.

Malinauskas, Giarra, Day, Burgreen, Herbertson, Stewart. Validation of CFD techniques used to 

evaluate medical devices: Interlaboratory study #2 – FDA benchmark blood pump model. 

American Society for Artificial Internal Organs - ASAIO annual conference, Washington, DC. 

Abstract: ASAIO J, 57(2):93, June 10-12, 2011.

Hariharan, Giarra, Reddy, Day, Manning, Deutsch, Myers, Stewart, Burgreen, Paterson, 

Malinauskas. Multi-laboratory uncertainty analysis of PIV-measured flow quantities relevant to 

blood damage in the FDA nozzle model. ASME 2011 Summer Bioengineering Conference 

Farmington, PA, June 22-25, 2011. (Extended abstract published in proceedings.)

Gammell PM, Liu Y, Maruvada S, Wear KA, Harris GR. Phase measurement with a simplified 

ultrasonic time delay spectrometry system. 38th Annual Review of Progress in Quantitative 

Nondestructive Evaluation, University of Vermont, Burlington, Vermont, July 2011.

Gammell PM, Liu Y, Maruvada S, Harris GR. Detector module for a simplified ultrasonic time 

delay spectrometry system. 38th Annual Review of Progress in Quantitative Nondestructive 

Evaluation (QNDE), University of Vermont, Burlington, Vermont, July 2011.

McCabe J, Burton E, Morgan A, Budinich C, Woodard G, Liu YB, Myers M, Moratz C. Mouse 

blood-brain barrier integrity and neuro-immune sequelae from non-impact pressure alterations by 

high-intensity focused ultrasound. Neurotrauma Symposium, 29th Annual National, Hollywood 

Beach, FL, July 10-13, 2011.

Moratz C, Burton E, Morgan A, Schrot J, McCarron R, Liu YB, Myers M, McCabe J. Rat bloodbrain barrier disruption and neuroimmune alterations from non-impact pressure alterations by 

high-intensity focused ultrasound and blast overpressure shock tube exposure. Neurotrauma 

Symposium, 29th Annual National, Hollywood Beach, FL, July 10-13, 2011.

Dreher MR , Sharma1 KV, Woods DL, Reddy G, Donahue D, Levy E, Karanian JW, Chiesa OA, 

Pritchard W, Tang Y, Willis S, Lewis AL, Wood BJ. Drug tissue penetration and coverage from 

doxorubicin eluting radiopaque embolization beads, Controlled Release Society, 38th Annual 

Meeting and Exposition, August 1, 2011. 

Marrey R, Gong XY, Nagaraja S, Dreher M, Weaver J, Gupta S, Rebelo N. Computational 

considerations for stent non-radial fatigue. FDA/NHLBI/NSF Fourth Annual Workshop on 

Computer Methods for Medical Devices, Silver Spring, MD, September 2011.

Lao C. A predictive model for cancer and non- cancer mortality in beagle dog study. 

FDA/Industry Statistics Workshop 2011, Washington, DC, September 19-21, 2011.

Woods T. FDA safety guidelines for medical devices in the MR environment. Biomedizinische 

Technik, the German Biomedical Conference, Technical Committee on MR Technology in 

Medicine, September 28, 2011. 

Liu C, Chinnakonda M, Duraiswamy N. Fluid-structure interaction analysis of a prosthetic aortic 

valve using abaqus/explicit smoothed particle hydrodynamics. ASME Frontiers in Medical 

Devices Conference, Irvine, California, September 2011.
69

Chen C, Khismatullin DB, Liu Y, Maruvada S, Myers M. Ex Vivo Study of ethanol enhanced 

cavitation activity in tissue exposed to high intensity focused ultrasound. Biomedical Engineering 

Society 2011 Annual Meeting, Hartford, CT, October 12-15, 2011.

Choi J, Reipa V, Goering P, Hitchins V, Malinauskas R. Physicochemical characterization and in 

vitro hemolysis evaluation of silver nanoparticles. AIChE (American Institute of Chemical 

Engineers) conference, Minneapolis, MN, October 16-21, 2011.

Harris GR. Piezoelectric polymer hydrophones and the regulation of medical diagnostic 

ultrasound devices by the U.S. Food and Drug Administration. (Invited), Joint Meeting of 

Washington DC Chapter of Acoustical Society of America and The Catholic University of 

America School of Engineering, Washington, DC, November, 2011.

Dornish M, Kaplan D. Tissue engineered medical product standardization – the ASTM 

International Committee F04. TERMIS-NA (Tissue Engineering and Regenerative Medicine 

International Society - North America) Annual Meeting. Houston, TX, December 11, 2011. 

Ferlin KM, Fisher JP, Kaplan DS, Centrifugation adhesion assay for characterizing the phenotype 

of chondrocytes. TERMIS-NA (Tissue Engineering and Regenerative Medicine International 

Society - North America) Annual Meeting. Houston, TX, December 11, 2011. 

Office of the Director 

Malghan S. Howard University, School of Pharmacy, Graduate school seminar- Nanotechnology 

regulatory science challenges and research directions, October 21, 2011. 

Malghan S. NIST-ANSI, International Workshop on Challenges to increased use of documentary 

nanotechnology standards, Nanotechnology Standards: Regulatory Science Applications at FDA, 

December 13, 2011. 
70

APPENDIX C – OSEL Academic Affiliations 

January 1, 2011 – December 31, 2011

Agrawal, Anant Virginia State University

Department of Mathematics 

 and Computer Science

Member, Master’s thesis committee

Badano, Aldo, Ph.D. University of Maryland, College Park 

Adjunct Prof 

Fischell Department of Bioengineering 

Bassen, Howard I. University of Maryland

College of Engineering

Lecturer

Dair, Benita J., Ph.D. University of Maryland

Fischell Department of Bioengineering

Adjunct Professor

Di Prima, Matthew, Ph.D. University of Texas at Dallas

School of Engineering and Computer Science

Visiting Researcher 

Dreher, Maureen, Ph.D. University of Maryland

Fischell Department of Bioengineering

Adjunct Professor

Goering, Peter L., Ph.D. University of Maryland

School of Medicine 

Baltimore, MD

Adjunct Professor 

The George Washington University

Department of Biological Sciences

Washington, DC

Adjunct Associate Professor 

Gray, Richard, Ph.D. University of Alabama at Birmingham
71

Department of Biomedical Engineering

Associate Professor

University of Alabama at Birmingham

Center for Glial Biology in Medicine

Scientist

Vanderbilt University

Department of Biomedical Engineering

Adjunct Associate Professor

Vanderbilt University

Vanderbilt Institute for Integrative Biosystems 

 Research and Education

External Associate

Ilev, Ilko, Ph.D. University of Maryland

Fischell Department of Bioengineering

Adjunct Professor

George Washington University

Department of Electrical 

 and Computer Engineering

Doctoral Thesis Committee

Jetley, Raoul, Ph.D. University of Arkansas at Little Rock

Department of Computer Science

Adjunct Faculty Member, and 

Member, Doctoral Dissertation Committee

Kainz Wolfgang, Ph.D. University of Houston

Department of Electrical and Computer

Engineering

Member, Doctoral thesis committee

Krauthamer, Victor, Ph.D. Uniformed Services University of the Health 

 Sciences

Department of Anatomy, Physiology, and 

 Genetics

Adjunct Assistant Professor

American University

Department of Biology

Adjunct Associate Professor

George Washington University

Department of Biology
72

Adjunct Associate Professor

Mehrabi, Ali, Ph.D. Strayer University

Adjunct professor

Undergraduate Math

Stratford University

Adjunct professor

Graduate and Undergraduate courses in 

Networking, CIS, MIS, and 

Telecommunications

Myers, Kyle J., Ph.D. University of Arizona

Optical Sciences Center

Adjunct Professor 

Georgetown University Medical

Department of Radiology

Adjunct Associate Professor 

Myklebust, Joel, Ph.D. George Washington University

Department of Electrical

 and Computer Engineering

Adjunct Assistant Professor

Nagaraja, Srinidhi, Ph.D. University of Maryland

Fischell Department of Bioengineering

Adjunct Professor 

Petrick, Nicholas, Ph.D. University of Michigan

Medicine School

Adjunct, Research Assistant Professor

Pfefer, T. Josh, Ph.D. University of Maryland

Department of Chemical and Biomolecular 

Engineering 

Doctoral thesis committee

Rajan, Sunder, Ph.D. Georgetown University Medical

Department of Radiology

Adjunct Associate Professor
73

Sapsford, Kim E., Ph.D. University of Maryland

Department of Bioengineering 

Adjunct faculty 

Waynant, Ronald W., Ph.D. Catholic University of America 

Electrical Engineering Department 

Adjunct Associate Professor 

Uniformed Services University 

 of the Health Sciences 

Adjunct Professor

Wear, Keith A., Ph.D. Georgetown University

Radiology Department

Adjunct Professor

Henry M. Jackson Foundation 

 for the Advancement of Military Medicine

Guest Scientist

Weininger, Sandy, Ph.D. Drexel University

Lecturer and course/program developer
74

APPENDIX D – OSEL Science Sharing Seminars

January 24, 2011 – October 17, 2011 

January 24

Contact Lens-Related Eye Infections: How We Got Here, Where We Are Going

Megan Shoff, Ph.D. (OSEL) 

March 7 

Tissue Imaging in Pathology: Quantitative Analysis of Biomarker Expression 

Mario Gavrielides, Ph.D., OSEL 

March 8

Computational Modeling in Device Regulation: Prospects for the Future

Sandy Stewart, Ph.D., OSEL 

March 21

Tissue Imaging in Pathology: The Challenge of Color Reproduction from Acquisition to Display 

Wei-Chung Cheng, Ph.D. (OSEL) 

April 4 

Electrical Activity and Wave Propagation in the Heart, with Application to Defibrillators and 

Pacemakers 

Richard A. Gray, Ph.D. (OSEL) 

April 18

Postmarket Surveillance Using Administrative Billing Data to Evaluate the Safety and 

Effectiveness of Uro-Gynecological Mesh 

Cara Krulewitch, CNM Ph.D., FACNM (OSB) 

May 2 

The Use of Quantitative Decision Analysis to Assess the Optimal Time to Remove a Temporary 

Device: the IVC Filter Case 

Telba Irony, Ph.D. (OSB) 
75

May 16

Diagnostic Ultrasound: Bioeffects, Safety, Regulation, and Prudent Use 

Jerry Harris, OSEL, Shahram Vaezy, OIVD, and Robert Phillips (OSEL) 

June 13

Innovative Optical Methods for Cancer Detection and Retinal Imaging 

Josh Pfefer, Ph.D. (OSEL) 

June 27

From Fluids to Goops to Solids: Characterization of Hydrogels and Implications for 

Performance 

Katherine Vorvolakos, Ph.D. (OSEL) 

July 11

Artificial Pancreas: Challenges with Glucose Sensors, Insulin Pumps, and Algorithms 

Arleen Pinkos, MT(ASCP) (OIVD), Charles “Chip” Zimliki, Ph.D. (ODE), and Irada Isayeva, 

Ph.D. (OSEL) 

July 25

The Infusion Pump Initiative: A Holistic Approach to Developing Better Infusion Pumps 

Victoria Wagman (OCD), Al Taylor (OSEL), Anthony D. Watson, BS, MS, MBA (ODE), 

Kathleen Cummings (OSB), Valerie A. Flournoy, MS (OC) 

August 8

Computational Toxicology as a Tool for Biocompatibility Reviews 

Ron Brown (OSEL) 

August 22 

Advanced Laser and Optical Technologies for Developing Innovative Test Methods in 

Biomedicine 

Ilko Ilev, Ph.D. (OSEL) 
76

September 19 

Automated Surveillance to Detect Post-Procedure Safety Signals of Approved Cardiovascular 

Devices 

Nilsa Loyo-Berrios, Ph.D. (OSB) 

October 3 

UV Bioeffects in Humans – Fundamentals of Tanning Process and Deleterious Effects of UV on 

Skin

Janusz Beer, Ph.D. (OSEL) 

October 17 

Electrical Stimulation of Neural Tissue 

Victor Krauthamer, Ph.D. (OSEL), Thomas Radman (ODE) 
77

APPENDIX E – Laboratory Leaders 

ü DIVISION OF BIOLOGY

Division Director: Marilyn Lightfoote (301) 796-0235

Deputy Director: Kevin Milne* 

· Toxicology and Biocompatibility: Peter Goering (301) 796-0253

· Biomolecular Mechanisms (molecular biology, immunology, allergy, cell biology, 

genomics/genetics): Steve Wood* (301) 796-0243

· Cardiovascular & Interventional Therapeutics: John W. Karanian (301) 210-4247 

· Emerging Biosensors and Biotechnologies: Kim Sapsford (301) 796-0311 

· Infection Control: Vicki Hitchins (301) 796-0258

ü DIVISION OF CHEMISTRY AND MATERIALS SCIENCE

Division Director: Dinesh Patwardhan (301) 796-2622

Deputy Director: Benita Dair (301) 796-2614

· Active Materials: Martin (Ken) McDermott (301) 796-2621

· Materials Performance: Benita Dair (301) 796-2614

ü DIVISION OF ELECTRICAL AND SOFTWARE ENGINEERING

Division Director: Al Taylor (301) 796-2583

Deputy Director: Brian Fitzgerald (301) 796-2579

· Electrical Engineering: Vacant

· Software (Research): Raoul Jetley (301) 796-2547

· Software (Regulatory Support): Joseph Jorgens (301) 796-2588

ü DIVISION OF IMAGING AND APPLIED MATHEMATICS

Division Director: Kyle J. Myers (301) 796-2562

Deputy Director: Nicholas Petrick (301) 796-2563

· Image Analysis: Nicholas Petrick (301) 796-2563

· Imaging Physics: Aldo Badano (301) 796-2534

· Ionizing Radiation Metrology: Mary Walker (301) 796-2558

ü DIVISION OF PHYSICS

Division Director: Victor Krauthamer (301) 796-2474

Deputy Director: Brian Beard (301) 796-2469

· Biophysics: Sunder Rajan (301) 796-4194

· Electromagnetic and Wireless Technologies: Howard Bassen (301) 796-2472

· Optical Diagnostic Devices: Joshua Pfefer (301) 796-2494

· Optical Therapeutics and Medical Nanophotonics: Ilko Ilev (301) 796-2489

· Functional Performance and Device Use Laboratory: Karen Siegel (301) 796-0653
78

ü DIVISION OF SOLID AND FLUID MECHANICS

Division Director: Laurence Grossman (301) 796-2502

Deputy Director: Jon Casamento (301) 796-2499

· Fluid Dynamics: Laurence Grossman (301) 796-2502

· Solid Mechanics: Terry Woods (301) 796-2503

· Ultrasonics: Gerald Harris (301) 796-2508

* denotes Acting
79

APPENDIX F – OSEL Organization Chart