RepoRt pRepaRed by:

Anastasiya Batrachenko, Semiconductor Research Corporation and Duke University

Ralph K. Cavin, III, Semiconductor Research Corporation

Daniel J.C. Herr, Semiconductor Research Corporation

Celia I. Merzbacher, Semiconductor Research Corporation

Victor Zhirnov, Semiconductor Research Corporation

acknowledgements

We thank the attendees at the 2nd Bioelectronics Roundtable held March 25-26, 2010 for their active participation

and thoughtful contributions to this report. Comments of Drs. Herbert Bennett, Michael Gaitan, John Kasianowicz,

Wentai Liu, Brian Nablo, Joe Reiner, Joey Robertson, David Seiler, and Lloyd Whitman are gratefully acknowledged.

We also wish to thank the Howard Hughes Medical Institute (HHMI) for generously hosting the workshop at its Janelia

Farm Research Campus in Ashburn, VA. In particular, we thank Kevin Moses and Janine Stevens for invaluable

support. Stacey Shirland is thanked for her support of both the workshop and the preparation of this report.

table of contents

executive summary 1

Introduction 3

High Impact opportunities & grand Research challenges

• Personalized Medical Diagnostics & Monitoring 9

• Implantable Medical Devices & Prosthetics 12

• Medical Imaging 15

summary message: Research priorities & key Recommendations 17

appendices

Appendix A | Influential Publications in Bioelectronics 20

Appendix B | Bioelectronics Research Resources 21

Appendix C | Agenda for 2nd Bioelectronics Roundtable Meeting 23

Appendix D | Attendee List for 2nd Bioelectronics Roundtable Meeting 24

Appendix E | Roundtable Participant Inputs on Potential Applications & Corresponding Research Needs 25

Appendix F | Proposed Framework for a Bioelectronics Research Initiative 36

1

executive summary: convergent bioelectronics opportunities

Technological advances at the intersection of biology/medicine and semiconductor electron-

ics — the area of “bioelectronics” — have the potential to transform healthcare, strengthen

national and homeland security, and help protect our environment, food and water supplies.

As semiconductor devices continue to become smaller yet more functional, we envision

implantable prosthetics that restore quality of life, lab-on-a-chip tools that provide sensitive

and selective identification of pathogens and biomarkers for disease, and imaging tools

that are portable and less costly. Trends that are driving demand include aging populations

in developed countries, rising health care costs, and lack of access to medical care in de-

veloping countries and remote areas. Targeted bioelectronics research can provide signifi-

cant societal and economic benefits.

This report follows a 2009 SRC report entitled Framework for Bioelectronics Innovation and

Discovery, which outlined the range of bioelectronics related applications. Based on a work-

shop in March 2010 that convened industry and government experts, this report updates

the earlier report and identifies priority research opportunities that can advance discovery

and enable innovation in the field. Workshop participants identified research opportunities

within the broad categories of ex vivo, in vivo, and imaging applications that represented

synergistic breakthrough opportunities for the semiconductor and biotechnology communi-

ties. These identified opportunities exhibit significant commercialization, job creation and

economic impact potential. Among the research opportunities that emerged, those that

were given highest priority by the diverse workshop participants from industry and govern-

ment fell into the following three areas in order of priority.

1. personalized medical diagnostics and monitoring. Personalized medical diagnostics

and monitoring represents the greatest near-term application opportunity. This area in-

cludes multimodal (optical, chemical, electronic) single molecule detection systems that

are capable of detecting low concentrations of molecules in “dirty” environments, such

as blood. It also includes label-free detection, ideally with single molecule resolution,

which could be realized using sensors that leverage semiconductor technology. Such ex

vivo applications are more readily brought to market.

2. Implantable medical devices and prosthetics. The second highest ranked research

area was neural-electronic interfaces and prosthetics-related research that would enable

reliable and robust implantable devices. A key issue in this area is biotic-abiotic inter-

faces that do not degrade over time.

2

3. medical imaging. High impact research opportunities in medical imaging fall in two

areas. One area is high-resolution in vivo imaging of small populations and clusters of

cells, or even within a single cell. The second area is portable and affordable imaging

systems that can be operated in settings outside the clinic, including remote, under-

served regions.

Addressing the identified challenges requires targeted, application-specific research and

advances in crosscutting areas, such as metrology in biological systems at sub-cellular to

organ and system levels; understanding and controlling biotic/abiotic interfaces to insure

biocompatibility and to manage biofouling; selective, sensitive and stable biosensors;

compact imaging sources; and electronics (including for wireless communications) with low

power requirements and enhanced signal to noise characteristics.

The synergistic, collaborative and interdisciplinary engagement of key stakeholders in the

“innovation supply chain” will accelerate progress and facilitate the transition of university

research to practical application and commercialization. Success requires strategic participa-

tion, contributions and innovation from academia, clinicians, industry sectors, federal labo-

ratories and other government funding and regulatory agencies. Semiconductor Research

Corporation (SRC) has a proven track record for creating consortia that 1) catalyze innovative

technology options through university research and transfer them to industry participants, 2)

build public-private collaborative research enterprises involving all stakeholders and 3) estab-

lish a pipeline of relevantly educated graduates who become the future industry workforce

and technology leaders.

The time for creating a global consortium is now. Bioelectronics research is taking place

around the world, with especially rapid growth in Asia. Those who wish to stay at the lead-

ing edge — whether in government, industry or academia — can gain advantage by working

together and synergistically leveraging their respective strengths.

3

A confluence of scientific and technological advances at the intersection of semiconduc-

tor electronics and biology points to novel applications in fields ranging from medicine and

assistive technologies to homeland security and environmental protection. Innovation in the

semiconductor industry has allowed the trend known as Moore’s Law to continue, produc-

ing smaller and cheaper devices that provide better performance and greater functionality.

At the same time, our understanding of biology and the biological basis of disease at the

molecular, cellular, tissue and system levels is growing exponentially.

Combining knowledge and technology at the leading edge of biology and electronics—the

area referred to as “bioelectronics” — can be part of the solution to challenges arising from

a variety of trends, including aging populations, rising healthcare costs, the growing number

of injured veterans, and the persistent lack of access to basic medical care in developing

countries and remote areas. Beyond healthcare, there are many other applications of bio-

electronics. For example, concerns are growing over safety, security and quality of the food

supply. Various pathogens can be introduced at many points along the path from the ocean

or field to the processing facility, market and table. And fraud in the food industry — from

wine and olive oil to cheese and seafood — is a rapidly growing problem for the industry.

This report builds upon an earlier report entitled A Framework for Bioelectronics Discovery

and Innovationa, which outlined the broad range of opportunities and challenges in this

emerging area. Here we narrow and prioritize among the options, based on inputs from

industry and government experts. The aim is to provide guidance for the development of

basic research programs that will enable technological progress for synergistic bioelectron-

ics applications that can have widespread social and economic impact, by creating new

technologies, products, businesses and jobs.

Within the broad spectrum of bioelectronics applications, this report focuses on those

in the area of medicine and healthcare, where progress will open the door for significant

advances in the ability to detect, diagnose and treat disease, while avoiding many adverse

side effects. Ultimately, the goal is to prevent and treat illness early and affordably, and

on a personalized basis. Moreover, bioelectronics holds the promise for enabling a range

of prosthetics and other assistive technologies that can improve the lives of persons with

disabilities. There are many examples of “smart” electronics that improve healthcare and

Biomedical aNd HealtHcare applicatioNs:

primary drivers for Bioelectronics

a www.src.org/emerging-initiative/bioelectronics/reports

Introduction

4

quality of life, such as pacemakers, image-guided and robotic surgery, and programmable

insulin pumps. But there are enormous opportunities yet to be addressed. While clinical

applications represent large, high-impact markets, many advances will first be applied in

biomedical research, where they can advance knowledge and understanding and be further

developed for treating patients.

Although it is difficult to project the economic benefits at this early stage of research, the fol-

lowing figures for some healthcare costs that could be impacted by bioelectronics provides a

sense of the magnitude of potential markets and benefits to individuals and society.

• In 2010 an estimated 1.5 million new cases of cancer were diagnosed and over 570,000

cancer deaths were reported in the United States. The National Institutes of Health (NIH)

estimates these cases cost nearly $100 billion in direct medical expenses and $160 bil-

lion more in lost productivity.

• An estimated 22 million Americans suffer from heart disease and about 460,000 die

from heart attacks each year (about 1 in 5 deaths). NIH estimates that in 2008, heart

disease cost an estimated $172.8 billion in direct medical expenses and an additional

$114.5 billion in indirect costs.

• An estimated 17.9 million Americans are diagnosed with Type 2 diabetes and millions

more are undiagnosed. The American Diabetes Association estimates that medical costs

associated with diabetes were $116 billion in 2007, with an additional $58 billion in

indirect costs.

• According to the National Centers for Health Statistics, each year the number of Ameri-

cans suffering from chronic pain is more than those who have diabetes, heart disease

and cancer combined—over 75 million. NIH estimates the direct and indirect costs of

chronic pain in the United States to be $100 billion annually.

The 2009 Framework for Bioelectronics Discovery and Innovation report contains an analysis

of research activity in the area of bioelectronics based on publications. This report pro-

vides updated data on the number of publications and citations, as well as the geographi-

cal distribution of authors, as a tool to assess changes in regional publication momentum

trends. As before, the Science Citation Index ExpandedTM (SCIE), available through the Web

of Science®, was used to identify bioelectronic*-related publication trends, where the ‘*’

represents a wildcard search feature in the title or abstract. The total number of publications

BioelectroNics researcH is a GloBal eNterprise

Figure 1. Number of publications (left) and citations (right) with ‘bioelectronic*’ in the title or abstract by year (as of August 2010).

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5

from 1912, when the first bioelectronics paper appeared, through August 2010 is 673, up

from 548 as of January 2009. Since 1991 there has been a noticeable number of bioelec-

tronics papers published each year, as shown in Figure 1. Because the term bioelectronics is

not used universally to describe research at the intersection of biology and electronics, the

actual number of publications in this field is much greater.

The geographic location of bioelectronics research has shifted significantly in the 18

months since the last analysis. Figure 2 shows that the United States and Germany remain

the two countries that have the greatest number of publications since 1991, while China

has moved from sixth to third highest, overtaking South Korea, Italy and Japan. South

Korea also moved past Italy and Japan into fourth place. The number of papers over the

intervening 18 months is also shown in Figure 2, highlighting the dramatic surge in publica-

tions from China. Figure 3 shows the distribution by region. The increased activity in China

and South Korea led to an increase in the fraction of papers by Asian researchers from 23

percent 18 months ago to 28 percent today. The increased share of publications from Asia

is paralleled by a decrease in the fraction from Europe, which went from 43 percent to 37

percent. The percentage from the United States and rest of the world has remained roughly

steady. A list of highly cited bioelectronics publications is shown in Appendix A.

Another measure of the emphasis being placed on bioelectronics research is the large

number of programs, centers and facilities at universities and other research institutions

worldwide. Selections of these entities are listed in Appendix B.

Figure 3. Distribution of publications with ‘bioelectronic*’ in the title or abstract by region.

OTHERS 14%

ASIA 28%

EU COUNTRIES 37%

USA 21%

Figure 2. Number of publications with “bioelectronic*” in the title or abstract by country since 1991 (Ieft) and since January 2009 (right).

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6

Realizing the potential of bioelectronics depends on the actions of diverse stakeholders. It

requires collaboration among researchers in various disciplines, including the life and physi-

cal sciences and engineering, along with clinicians and other practitioners. It also requires

the involvement of technical experts from the semiconductor electronics and biomedical

industries, who can translate research results into practical applications and useful prod-

ucts. Government agencies — such as NIH, National Institute for Standards and Technology

(NIST), National Science Foundation (NSF), Defense Advanced Research Projects Agency

(DARPA), and Food and Drug Administration (FDA) — will play crucial roles in supporting and

guiding this area of research and development. Ideally these efforts should be coordinated

to expedite progress in both research and application. SRC is ideally equipped to coordi-

nate such collaboration.

SRC is a recognized leader in managing collaborative research and has developed effi-

cient, effective and proven mechanisms and processes for creating and managing industry

consortia, setting direction, managing and coordinating the research, and disseminating

the results. SRC’s primary objectives are to support the competitiveness of its company

members (individually and collectively), explore new technologies, stimulate industry-

relevant academic research, promote greater academic collaboration, and sustain a pool

of experienced faculty and a pipeline of relevantly educated students. Since its inception in

1982, SRC has managed over $1.5 billion in basic academic research at over 198 universi-

ties worldwide and supported over 8400 students, who have gone on to become the next

generation of leading-edge researchers, technology innovators and industry leaders. Pro-

cesses and infrastructure developed by SRC identify and communicate industry’s collective

basic research needs, connect the academic faculty and student researchers with industry

“users”, support university research with high impact potential, and deliver early results to

members via online systems.

A first step in establishing a consortium-based research program is to develop consensus

on research needs and opportunities. Two workshopsb — one in November 2008 and an-

other in March 2010 — brought together experts from government, industry and academia

to identify and prioritize research areas. The first workshop outlined the broad scope of bio-

electronics applications and identified a number of high priority research topics. Expert input

from that workshop is included in the Framework for Bioelectronics Discovery and Innovation.

At that workshop the strategic drivers most frequently cited were disease detection, disease

prevention and prosthetics. High priority research challenges were grouped into devices,

measurements and analyses, and technologies and are listed in Figure 4 (next page).

At the second Bioelectronics Roundtable held in 2010, attendees from industry and gov-

ernment agencies convened by invitation to discuss more specific research opportunities

potentially worthy of joint investment. The workshop agenda and invited participants are

shown in Appendices C and D. The 25 attendees included government representatives from

DARPA, FDA, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK),

National Institute for Biomedical Imaging and Bioengineering (NIBIB), NIST and NSF, as well

a coordiNated, collaBorative approacH

b Details and presentations from the workshops are available at www.src.org/emerging-initiative/bioelectronics

7

as private sector representatives from The Bosch Group, GE Healthcare, Howard Hughes

Medical Institute, IBM, Intel Corporation and Tokyo Electron Ltd.

The following section of this report describes three categories of high-impact market and

research opportunities discussed at the workshop: diagnostics (in vitro), implantable

devices and prosthetics (in vivo), and imaging. In each category, a number of research

topics that can have impact within five years are given. In the course of the workshop, a

broad range of topics was considered based on the contributions of participants. Detailed

descriptions of bioelectronics’ applications and associated research needs brought forward

by workshop attendees, as well as the benefits over other technologies and metrics of prog-

ress are listed in Appendix E. From these a set of priority research needs was developed.

In addition to the three categories, a fourth crosscutting area of research related to metrol-

ogy was identified. There is a growing need to develop device characterization and testing

methods that support each bioelectronics technology’s advancement through the innova-

tion pipeline and its transition to commercial applications. A strategic collaborative invest-

ment in relevant metrology research would enable access to appropriate characterization

tools with the required sensitivity, reliability and traceability, in time to impact the research

and development phases of emerging bioelectronics products. Examples of key character-

ization research challenge topic areas include communication, fluidics and the integration

of biomolecule sensors with chip-based platforms. This latter interdisciplinary topic inte-

grates the specificity and sensitivity of biomolecules for analyte detection with the signal

detection and processing power of semiconductors, etc.

Addressing the priority research outlined in this report will provide economic benefits,

including jobs, and lead to better medical treatments, healthcare and quality of life — and

doing so through a coordinated, collaborative approach can expedite progress. A potentially

priority researcH

looKiNG aHead

APPLICATIONSHealth care and medicine; Assistive

technologies; Biodetection for homelandsecurity; Food safety; Environmental

monitoring, etc.

MEASUREMENTTOOLS & METHODS

Sensitive; Selective; In situ;Real time; Noninvasive

SYSTEMSLab-on-a-chip;

Implants; Imaging; Sensors

TECHNOLOGIESMolecular recognition;

Signal processing; Platforms:arrays, sequencing, etc.

Figure 4. Bioelectronics applications are driving broad areas of precompetitive research in systems & devices, technologies, and metrology.

8

powerful approach is for industry to: form a consortium that agrees upon technical goals

and defines research needs; partner with aligned government agencies; and, through an in-

dependent organization, fund university research. Such a Bioelectronics Research Initiative

(BERI) delivers value to members in the form of research results and relevantly educated

talent. Partnership with government agencies, including regulatory agencies, can further

accelerate progress and ensure that research investments are in the most needed areas

and that results are translated efficiently. A proposed organization for the new consortium-

based initiative is shown in Appendix F. Such a collaborative approach leverages strengths

of industry, academia and government, and maximizes value for all parties.

9

High-Impact opportunities & grand Research challenges

An aging population, rising healthcare costs and increasing access are driving significant

changes in the human diagnostics and monitoring technology market. In the United States

the total market for personalized medicine, including diagnostics, monitoring and therapeu-

tics, currently is estimated at $232 billion and is projected to grow 11% annually, nearly

doubling in size by 2015 to a total of $452 billion, according to PricewaterhouseCoopers’

estimates.1 The core segment of the market — comprised primarily of diagnostic tests and

targeted therapies — is estimated at $24 billion and is expected to grow by 10% annually to

$42 billion by 2015.1

Early detection of disease or abnormality correlates with improved medical outcomes and

lower cost. Can an individual know of the onset of a disease before symptoms even ap-

pear? Can treatment be tailored for the individual’s specific condition, rather than an aver-

age population response? Personalized medicine may revolutionize healthcare by leveraging

knowledge of an individual’s biological information to guide the development of customized

treatments and long-term health programs. And personalized medicine promises to en-

able patients and healthcare providers to proactively predict, detect and prevent disease,

optimize prevention and treatment strategies, and reduce inefficiencies that adversely

impact patient care, clinical trials and healthcare costs. Examples of successful patient-

specific diagnostics currently in use include genome-based molecular screening of drugs,

and dosages for treating blood clots and certain types of colorectal and breast cancer. A

broader emphasis on individualized diagnostic tools will improve the quality of healthcare

by enabling the timely delivery of appropriate and customized therapies.

There is a growing need for multimodal, label-free, calibrated diagnostic tools that can

detect single — or low concentrations of specific — molecules in a “dirty” environment, such

as blood. This topic received the workshop participant consensus as the highest priority

bioelectronics-related opportunity. Integrated chemical, optical and electronic detection

systems using high-density arrays of sensors that leverage semiconductor technology could

provide rapid, low-cost screening, risk-mapping and diagnostic capability. For example, a

field-deployable screening tool using a protein microarray would facilitate the predictive and

timely detection and diagnosis of autoimmune diseases, cancers, infectious diseases, drug

resistance, bio-warfare agents, etc.

The state-of-the-art technology is improving, but is not yet sufficient. Current immunoassays

in clinical use typically measure proteins at concentrations above 10−12 molar (M).2 However,

for many cancers3, neurological disorders4,5 and early stage infections6 such as HIV, serum

marker protein concentrations range from 10-16 to 10-12 M. Recent work demonstrates the

feasibility of detecting 4*10-16 M concentrations of labeled prostate cancer-related proteins

persoNaliZed medical diaGNostics & moNitoriNG

10

Achieve sensor structure and response uniformity

Control and characterize surface passivation, interfaces

and chemistry

Standardize wireless sensing

Identify a low-cost solution for ensuring secure transmission

to a network

Develop robust packaging and integration options

Develop predictive models and guiding principles for

managing biological variations and noise

Develop green technology options for manufacturing

disposable devices that minimize environmental impact

Develop biocompatible semiconductor sensors that are

designed for specific molecular structures

Develop Si-based peptide arrays for detecting multiple analytes,

i.e., parallel peptide analyses

Develop multiplexed, low-power platforms

Concurrently develop metrology standards

Control and characterize surface passivation, interfaces

and chemistry:

• Selectively tune temporal absorption and affinity modulation

• Develop interface compatible anti-fouling technologies, i.e.,

for organic/organic, organic/inorganic and inorganic/inorganic

interfaces

Selectively functionalize sensors for multiplexed applications

for detection of at least 64 analytes

Develop reliable, label-free single-molecule (5-yr) and

multi-molecule (5+ yrs) biosensor arrays

Explore new materials for sensor systems

Integrate electronics, microfluidics and functionality

Ensure protection of the underlying CMOS circuitry in the

biological medium

Demonstrate manufacturing feasibility — rapid, flexible

prototyping facilities needed

Develop benchmarks (3-yr) and a roadmap (5-yr) of projected

parameter requirements that enable guiding principles

for system design

in serum, using gold nano-particles and DNA barcodes7 or an enzyme labeled assay with

~10-19 M sensitivity.8

Label-free assays are more challenging. While label-free DNA assays with femtomolar (fM)

sensitivity (10-15 M) have been demonstrated for some time, corresponding protein assays

remained orders-of-magnitude less sensitive. More recently, new approaches using silicon

nanowire devices and optical microcavities have pushed label-free protein assay sensitivities

to the fM and attomolar (10-18 M) ranges, respectively, in non-serum samples.

These promising results suggest tremendous market opportunities for highly selective,

real-time diagnostic and monitoring technologies. Targeted research is needed to explore

emerging families of label-free diagnostics and monitoring devices for applications with

high impact potential. The table below summarizes the workshop participants’ consen-

sus on critical near-term (three years) and longer-term (five years) research challenges

and objectives that would demonstrate a given technology’s commercialization and

manufacturing potential.

11

References:

1. PricewaterhouseCoopers’ Health Research Institute (2009). [The new science of personalized medicine]

http://www.pwc.com/personalizedmedicine and en.wikipedia.org/wiki/Personalized_medicine

2. Giljohann, D.A. & Mirkin, C.A., Drivers of biodiagnostic development, Nature 462 (2009), p. 461–464.

3. Srinivas, P.R., Kramer & Srivastava, Trends in biomarker research for cancer detection, Lancet Oncol. 2

(2001), p. 698–704.

4. Galasko, D., Biomarkers for Alzheimer’s disease – clinical needs and application, J. Alzheimers Dis. 8

(2005), p. 339–346.

5. de Jong, D., Kremer, B.P.H., Olde Rikkert, M.G.M. & Verbeek, M.M., Current state and future directions of neu-

rochemical biomarkers for Alzheimer’s disease, Clin. Chem. Lab. Med. 45 (2007), p. 1421–1434.

6. Barletta, J.M., Edelman, D.C. & Constantine, N.T., Lowering the detection limits of HIV-1 viral load using real-

time immuno-PCR for HIV-1 p24 antigen, Am. J. Clin. Pathol. 122 (2004), p. 20–27.

7. Thaxton, C.S. et al., Nanoparticle-based bio-barcode assay redefines “undetectable” PSA and biochemical

recurrence after radical prostatectomy, Proc. Natl. Acad. Sci. USA 106 (2009), p. 18437–18442.

8. Rissin, D., Kan, C., Campbell, T., Howes, S., Fournier, D., Song, L., Piech, T., Patel, P., Chang, L., Rivnak, A., Fer-

rell, E., Randall, J., Provuncher, G., Walt, D., & Duffy, D., Single-molecule enzyme-linked immunosorbent assay

detects serum proteins at subfemtomolar concentrations, Nature Nanotechnology, 28, 6 (2010), p. 595-599.

9. Nagel, M., Bolivar, P., Brucherseifer, M., et al., Integrated THz technology for label-free genetic diagnostics,

Applied Physics Letters, 80, 1 (2002), p. 154-156.

10. Arntz, Y., Seelig, J., Lang, H., et al., Label-free protein assay based on a nanomechanical cantilever array,

Nanotechnology, 14, 1 (2003), p. 86-90.

11. Patolsky, F., Zheng, G., Lieber, C., Fabrication of silicon nanowire devices for ultra sensitive, label-free, real-time

detection of biological and chemical species, Nature Protocols, 1, 4 (2006), p. 1711-1724.

12. Armani, A., Kulkarni, R., Fraser, S., et al., Label-free, single-molecule detection with optical microcavities,

Science, 317, 5839 (2007), p. 783-787.

12

Innovations in integrated circuit technologies are spurring a revolution in in vivo health-

care, thereby catalyzing significant growth in the ~$40 billion implantable medical device

market.1 Ideally, medical implants and prosthetics allow the recipient to be able to carry

out many daily activities unassisted — and with devices such as pacemakers, without even

thinking about the device once implanted.

A variety of conditions and disabilities have the potential to be addressed by medical im-

plants and prosthetics. Approximately 67 million Americans are afflicted with arthritis2 and

24 million have diabetes.3 Ten percent of the U.S. population (i.e., ~30 million people) will

experience a seizure in their lifetime.3 And several million individuals suffer from limb loss

or other orthotic impairments that require prosthetics, due to the impact of cardiovascular

disease, diabetes, traumatic injury, infection, tumors, nerve damage and congenital anoma-

lies.2 As the population ages over the next few decades, there will likely be an increase in

spinal injuries and paralysis, and a growing demand for associated orthotic services.4 Ad-

ditionally, each year, approximately 75 million Americans report suffering from pain lasting

more than 24 hours4. For the broader population, in vivo health monitoring, diagnostic and

automated drug delivery devices promise to sustain a person’s health by proactively ad-

dressing the early onset of infections and diseases and managing pain. These health and

demographic statistics paint a picture of the significant and growing need for robust and

reliable in vivo and integrated devices.

Key application opportunities for implantable bioelectronic devices include artificial organs,

prosthetics, health monitors, and automated drug and metabolite delivery devices. Given the

large and growing number of people with diabetes, and the disease’s potential for debilitat-

ing effects including blindness and limb loss, the artificial pancreas is among the highest

impact artificial organs. In prosthetic systems, long-term sensitivity, reliability and functionality

of biotic/abiotic interfaces is vital. In particular, controlling and quantitatively monitoring the

chemical, electrical and optical interfaces between neural and engineered systems is critical to

the performance of neural implants and prosthetics.5

Implantable or wearable healthcare monitors have the potential to continuously assess mul-

tiple conditions and biomarkers and network to the appropriate service providers for real-time

personal care. The following implantable monitoring devices appear to exhibit the highest

impact potential: glucose monitor, cardiac blood flow and composition monitors, monitors for

detecting human brown adipose tissue, integrated optical electrical neurophysiology probes,

and selective biosensors, e.g., for early cancer detection. Such technologies promise to speed

diagnosis and reduce the need for costly lab tests.

Finally, integrated, automated drug and metabolite delivery devices could be tailored to an

individual’s specific needs to offer optimal dosing with minimal side effects. This latter set

of applications could revolutionize personal medicine by providing timely, targeted thera-

peutics to alleviate symptoms and pain in persons with infections, chronic diseases such

as cancer and malaria, physical and psychological trauma, and genetic disorders such as

cystic fibrosis, sickle-cell disease, Tay-Sachs disease, Niemann-Pick disease, spinal muscu-

lar atrophy, Roberts Syndrome, etc.

implaNtaBle medical devices & prostHetics

13

While the potential benefits of implantable bioelectronic devices are significant, the risk

of trauma and chronic side effects must be addressed for these technologies to be widely

adopted. Ensuring that the implanted device is highly biocompatible can minimize some

adverse consequences. According to one definition, “An implant can be considered to be

biocompatible if 1) it does not evoke a toxic, allergic or immunologic reaction, 2) it does not

harm or destroy enzymes, cells or tissues, 3) it does not cause thrombosis or tumors, and

4) it remains for a long term within the organism without encapsulation or rejection.”6 In

general, the interfaces between the biomatter and the sensing surfaces are critical. For ex-

ample, in some prosthetic devices actuation and control functionality degrades significantly

during the first two years of use largely due to biofouling and biodegradation.7 The ability

to form stable, immobilized, micro-scaled interfaces that contact individual nerves with

minimal tissue damage, immune response and signal noise, would significantly reduce the

variability, degradation and functional attenuation of heterogeneous biotic-abiotic systems.

If stability is not feasible, embedded nanosensors might allow for compensation over time.

Other challenges include power generation, storage and management, hermetically sealed

packages, and maximizing the functionality of embedded microsystems, i.e., sensing, sig-

nal processing, multiplexing, communication and actuation.

The table on the following page summarizes a set of critical near- and longer-term research

opportunities that would address many of the strategic research challenges facing implant-

able bioelectronic devices with significant market potential.

14

References:

1. Biocompatible Materials Drive the Success of Implantable Medical Devices | ECN: Electronic Component News

2. http://www.aboutonehandtyping.com/statistics/, accessed August 13, 2010.

3. http://www.diabetes.org/diabetes-basics/diabetes-statistics/, accessed August 13, 2010.

4. http://www.painfoundation.org/newsroom/reporter-resources/pain-facts-figures.html, accessed August 13, 2010.

5. M. P. McLoughlin, DARPA Revolutionizing Prosthetics 2009, http://www.dtic.mil/cgi-bin/GetTRDoc?Location=U2&d

oc=GetTRDoc.pdf&AD=ADA519193/(January 2009), accessed August 13, 2010.

6. http://www.opcareers.org/assets/pdf/TrendsFINAL.pdf, accessed August 13, 2010.

7. S. Thanos and P. Heiduschka, Implantable bioelectronic interfaces for lost nerve functions, Progress in

Neurobiology, 55(5), pp. 433-461 (Aug 1998).

materials:

Coatings for implantable devices, including large-area thin

films and hermetically sealed packages

Biocompatible organic electronic materials and biotic/abiotic

interfaces that minimize rejection and immune response and

maintain cell viability

devices:

Sensors using organic semiconductors

Biocompatible devices designed to sense specific molecular

structures/biological targets

Devices for concurrent assessment of multiple biological

parameters

Adaptable algorithms for designing new devices

systems:

Architectures

Wireless communication

Hardware/software trade-offs

Fabrication:

High accuracy patterning of printable, degradable organic

electronics

Robust, reliable biotic/abiotic interfaces

Interface-compatible cleaning technology, i.e., for organic/organic,

organic/inorganic and inorganic/inorganic interfaces

Novel, adaptable, biocompatible and biomimetic materials

Artificial bioelectronic [nanomorphic] cells for in vivo sensing,

monitoring, diagnosis, etc.

Additional long-term challenges:

Soft-case approach (thin film coating) for hermetic sealing

and packaging

Close-loop architecture for hybrid integration of chemical

and electrical sensing and stimulation

High energy efficiency power source

15

Medical imaging is a powerful means of disease detection and diagnosis. There are many

modalities to chose from, including conventional radiography (x-rays), dual x-ray absorptiom-

etry (DXA), computed tomography (CT), ultrasound (US), magnetic resonance imaging (MRI),

positron emission tomography (PET), single photon emission tomography (SPECT), opti-

cal coherence tomography (OCT) and microscopy. Optical microscopy is usually applied to

pathological analyses. Clinical scans also often rely on chemical contrast agents to selec-

tively change tissue properties for easier biological characterization of any potential abnor-

malities. Each of the existing imaging techniques has its own strengths and deficiencies,

and a combination of scans can greatly improve diagnostic accuracy. Yet every additional

scan contributes to the cost of patient care, and the use of contrast agents may result in

undesired side effects. A single diagnostic imaging procedure can cost $3000 or more

for CT and MRI modalities1. Yet, CT and MRI are currently some of the more informative

and widely used imaging tools in the clinic, with over 68 million CT scans performed in the

United States in 2008, an increase of 10 percent from 20072. Even if cost is not an issue,

the frequency and number of possible imaging procedures is limited for each patient by fed-

eral and state safety regulations in order to keep the radiation exposure within biologically

tolerable levels. Therefore, effective yet low-maintenance and low-risk imaging tools are a

very strong need for successful medical care.

A primary driver of medical imaging is early detection of cancer. The ultimate goal is catch-

ing the disease before it even fully develops, i.e., identifying the troublesome cells before

they become cancerous. Current imaging technology is capable of reliably distinguishing le-

sions down to ~1 mm3 in size3. Unfortunately, such a lesion size is achieved long after the

initiation of the angiogenic switch, which supplies the tumor with its own blood vessels and

allows the disease to metastasize. An imaging method that could detect malignant cells

before the angiogenic switch stage would be a key to avoiding progression and effectively

eliminating illness from cancer.

In addition to sensitivity and safety, ease and cost of maintenance and accessibility (both

geographic and economic) are crucial factors for any successful imaging technology.

Impressive advances have been made in making some modalities more compact, e.g.,

x-ray gear that fits into an army backpack and ultrasound modules the size of a laptop.

However, other versatile clinical diagnostic tools, such as PET/CT and MRI scanners, still

remain quite bulky and expensive to support. A new MRI scanner may cost $2-3 million

dollars and annual follow-on servicing and technician costs may approach $1 million per

year4. Currently, CTs and MRIs are the most capable tools for evaluating and tracking a

wide range of medical abnormalities, such as cancerous lesions, cardiovascular abnormali-

ties or neuronal degeneration. Yet their high construction costs and extensive maintenance

requirements strongly limit the accessibility of these potent imaging modalities at smaller

hospitals and private points of care, not to mention in remote, underserved areas.

Much research and development work remains to be done in designing accurate, acces-

sible and safe imaging tools. In particular, there is a growing need for high sensitivity, high

resolution, low-maintenance macroscopic imaging devices, as well as for in vivo single cell

medical imaGiNG

16

References:

1. <http://www.comparemricost.com/>, accessed on August 24, 2010

2. American Consumer News <http://www.americanconsumernews.com/2009/12/

medical-studies-suggest-too-many-ct-scans-increases-cancer-risk.html>, accessed on August 24, 2010

3. Wolbarst and Hendee. “Evolving and experimental technologies in medical imaging”. Radiology. 238:1,

January 2006

4. <http://en.wikipedia.org/wiki/Magnetic_resonance_imaging>, accessed on August 24, 2010

and single molecule imaging capabilities. Additional high priority opportunities include the

detection of rare small populations of cells below the resolution of conventional techniques

(such as the detection of small clusters of pancreatic beta cells), and the design of highly

portable ultrasonic and MRI scanners. There are also novel opportunities to explore cur-

rently underused parts of the electromagnetic spectrum. Terahertz imaging systems, for

example, have potential to expand even further the available technological arsenal to aid

security screening and early skin cancer detection. Currently, biopsy is still used as the

gold standard for the clinical evaluation of skin tissue lesions, even though its diagnostic

accuracy is far from absolute. This procedure also may cause the patient unnecessary pain

and emotional discomfort. Hence, the ability to accurately identify anatomical and metabol-

ic abnormalities at the single-cell level, or at least at the level of a microscopic cell cluster,

holds significant promise for effective and painless disease monitoring and treatment. In

the longer-term, bioelectronic—or nanomorphic—cells are envisioned that are capable of a

wide variety of health-related actions, from gene sequencing to the characterization of local

environments inside the body.

The success of diagnostic imaging relies on technological advances in data acquisition,

analysis, reconstruction and processing efficiency. Miniaturizing detection electronics and

the primary radiation sources, while accelerating reconstruction software capabilities, will

improve a scanner’s diagnostic capabilities and its portability and ease of maintenance. A

strategic, collaborative investment in imaging research would catalyze the creation of new

high performance and portable biomedical imaging technologies.

The following table highlights several of the key identified bioelectronics imaging-related

research challenges and opportunities.

Identify novel parallel-signal acquisition paradigms, together with enhanced data reconstruction and storage software and hardware

Design ultra-low power mixed-signal integrated circuits for high performance imaging equipment applications and operation

Develop novel materials for terahertz wave sources/receptors and lighter imaging magnets

Develop unique molecular marker-sensing techniques for nanoscopic detectors

Understand the radio and thermal deposition effects of THz radiation on tissue

17

summary message Research Priorities & Key Recommendations

The field of bioelectronics includes a range of diverse applications areas, each of which

has the potential for significant societal and economic impact. Experts at the workshop

identified research opportunities within the broad categories of ex vivo, in vivo and imaging

applications that had potential for high impact. Among the 20 research opportunities that

emerged, those that were given highest priority by the diverse workshop participants from

industry and government fell into the following three areas in order of priority.

1. personalized medical diagnostics and monitoring. Personalized medical diagnostics

and monitoring represents the greatest near-term application opportunity. This area in-

cludes multimodal (optical, chemical, electronic) single-molecule detection systems that

are capable of detecting low concentrations of molecules in “dirty” environments, such

as blood. It also includes label-free detection, ideally with single-molecule resolution, for

example using sensors that leverage semiconductor technology. Such ex vivo applica-

tions are more readily brought to market.

2. Implantable medical devices and prosthetics. The second-highest ranked research

area was neural-electronic interfaces and prosthetics-related research that would enable

reliable and robust implantable sensors and devices. A key issue in this area is biotic-

abiotic interfaces that do not degrade over time for high-impact applications, such as

functional prosthetics and diabetes management.

3. medical imaging. High-impact research opportunities in medical imaging fall in two

areas. One area is high-resolution in vivo imaging of small populations and clusters of

cells or even within a single cell. The second area is portable and affordable imaging

systems that can be operated outside the clinical setting, including in remote, under-

served regions. Wearable electronics, especially for cognition monitoring and the gaming

industry, is within this category.

Other research opportunities that were discussed (and which are detailed in Appendix E)

include:

• Artificial pancreas

• Terahertz imaging systems

• Neurophysiology probes

18

• Single-molecule diagnostics

• Digital point-of-care diagnostics

• Degradable, implantable bioelectronics chips, e.g., blood flow monitor

• Human brown adipose tissue detection

• Biosensors with high sensitivity, reliability and traceability

• Integrated chemical-optical-electrical-neurophysiology probes

• Multiplexed biomarker detection

• Stochastic sensing

• High-performance bio-signal/information processing

• Nanomorphic cell

• Measurements and standards for quantitative medical imaging

• Cell integration platform

• Power sources, such as rechargeable batteries

Many of these opportunities align with one of the top-ranked areas listed above. For ex-

ample, single-molecule and digital point-of care diagnostics, biosensors and multiplexed

biomarker detection align with personalized medical diagnostics and monitoring. Implant-

able medical devices include artificial pancreas, neurophysiology probes (including inte-

grated electro-optical devices), and degradable and implantable bioelectronic chips. Finally,

research on terahertz imaging systems and human brown adipose tissue detection could

be associated with opportunities in high-resolution imaging technologies.

In addition to these focused topics, there is a crosscutting need for characterization and

testing methods that support advancement of bioelectronics in general through the innova-

tion pipeline and transition to commercial applications.

These topics lay the foundation and provide a framework for more detailed discussions on

specific high-value collaborative research projects between the semiconductor electronics

and the biotechnology communities. The top-three ranked research topics, while highly rat-

ed, may represent different grades of potential commercial opportunity for each community.

For example, low volumes of high-margin devices and systems may enable some strategic,

high-value market opportunities, such as enhanced MRI technology, for the biomedical

community. Similarly, this community also realizes the commercial potential for low-cost

point-of-care or home diagnostic devices, which represent high volume, but lower margin

products. Correspondingly, a traditional commercialization success factor for the semicon-

ductor community is its ability to achieve high yields of high-volume products. Smaller runs

of high-margin products are possible, but may require new business models and innovative

fabrication methods. Given these considerations, personalized medical diagnostics and

monitoring appears to represent a clear and immediate initial point of traction between the

semiconductor electronics and biomedical technology communities. The other two high-

19

priority topics also warrant consideration. However, further discussions may be needed to

clarify the synergistic win-win for both communities.

Based on input of workshop participants and recognizing the strengths and concerns of

both the semiconductor and biomedical industries, the following findings and recommenda-

tions are offered as a means of strengthening the value of university research in the area

of bioelectronics — for both industry and government stakeholders.

Findings:

1. Advances in semiconductor electronics and biology/medicine are creating an opportuni-

ty for bioelectronic technologies that provide societal and economic benefits. With grow-

ing research activity worldwide, now is the time for academia, industry and government

to work together to achieve the research, education and development goals of each and

to overcome barriers to realizing these benefits.

2. A Bioelectronics Research Initiative based on SRC’s consortium model for the support

of collaborative, precompetitive research can facilitate and accelerate development of

future bioelectronics products.

3. For the Bioelectronics Research Initiative to succeed, the biomedical community has a

role to play in defining credible bioelectronics research targets and insertion metrics,

and in supporting clinical and regulatory infrastructure for testing selected application

opportunities. The semiconductor community provides infrastructure for designing and

fabricating high volume, nanoscaled and complex information processing technologies

for healthcare applications.

4. Each of the top-three priority topics listed above represents a multimillion dollar three-

to five-year initiative.

Recommendations:

The research opportunities identified and prioritized in this report represent a consensus of

diverse stakeholders from industry and government. The next step is to define, with key stake-

holders, the detailed research directions and specific research targets for each of the top-rated

synergistic research opportunities. The first focus group will clarify a set of research tasks that

would enable advancement in personalized medical diagnostics and monitoring, which is the

area of bioelectronics with the greatest impact potential in the five-year timeframe.

In addition, further consideration will be given to research needs in the area of neural-elec-

tronic interfaces, implantable devices, imaging small populations of cells, and portable high-

resolution imagers, which also represent areas that can benefit from greater collaboration.

Subsequent stakeholder discussions will clarify the specific research directions and research

targets for these additional high-priority opportunities.The goal is to launch well-targeted,

coordinated university research that leverages individual investments and provides high value

to both the electronics and biomedical industries by enabling new market opportunities and

creating jobs, and at the same time improving healthcare in a cost effective manner.

20

Publication Author(s) Citations

appendix a: Influential publications in bioelectronics

“Integration of layered redox proteins and conductive supports for bioelec-

tronic applications”, Angew. Chem.-Int. Ed. 39 (7): 1180-1218, 2000

I. willner and e. katz

Hebrew University, Jerusalem, Israel486

“Biological surface science”, Surface Science 500 (1-3): 656-677, 2002

b. kasemo

Chalmers University Technology,

Gothenburg, Sweden

364

“Probing biomolecular interactions at conductive and semi-conductive

surfaces by impedance spectroscopy: Routes to impedimetric immuno-

sensors, DNA-Sensors, and enzyme biosensors”, Electroanalysis 15 (11):

913-947, 2003

e. katz and I. willner

Hebrew University, Jerusalem, Israel354

“Supramolecular self-assembly of lipid derivatives on carbon nanotubes”,

Science 300 (5620): 775-778, 2003

c. Richard, et al.

University Strasbourg, France

Illkirch Cedex, France

289

“Control of the structure and functions of biomaterials by light”, Angew.

Chem.-Int. Ed. 35 (4): 367-385, 1996

I. willner and s. Rubin

Hebrew University, Jerusalem, Israel219

“Toward bioelectronics: Specific DNA recognition based on an

oligonucleotide-functionalized polypyrrole”, J. Am. Chem. Soc. 119 (31):

7388-7389, 1997

H. korri youssoufi, et al.

CNRS, France207

“Dielectrophoretic assembly of electrically functional microwires from

nanoparticle suspensions” Science 294 (5544): 1082-1086, 2001

kd Hermanson, et al.

University Delaware, Newark, DE

NC State University, Raleigh, NC

196

“Preparation and hybridization analysis of DNA/RNA from E-coli on

microfabricated bioelectronic chips”, Nature Biotechnology 16 (6):

541-546, 1998

J. cheng, et al.

Nanogen, Inc., San Diego, CA174

“Nanomaterial-based electrochemical biosensors” Analyst 130 (4): 421-

426, 2005

J. wang, Ucsd [Formely with NM

State University, Albuquerque, NM]173

“Towards genoelectronics: Electrochemical biosensing of DNA hybridiza-

tion”, Chemistry-Eur. J. 5 (6): 1681-1685, 1999

J. wang, Ucsd [Formely with

NM State University, Albuquerque, NM]166

“Chip and solution detection of DNA hybridization using a luminescent zwit-

terionic polythiophene derivative”, Nature Materials 2 (6): 419-U10, 2003

kpR nilsson and o. Inganas

Linkoping University, Sweden151

“Biomolecular electronics: Protein-based associative processors and

volumetric memories”, J. Phys. Chem. B 103 (49): 10746-10766, 1999

RR birge, et al.

Syracuse University, Syracuse, NY132

“The Application of Conducting Polymers in Biosensors”, Synthetic Metals

61 (1-2):15-21, 1993

pn bartlett and pR birkin

University Southampton, England132

“Electrical contact of redox enzyme layers associated with electrodes:

Routes to amperometric biosensors”, Electroanalysis 9 (13) 965-977,

1997

I. willner, et. al.

Hebrew University, Jerusalem, Israel131

“Biocatalyzed amperometric transduction of recorded optical signals

using monolayer-modified Au-electrodes”, J. Amer. Chem. Soc. 117 (24):

6581-6593, 1995

I. willner, et. al.

Hebrew University, Jerusalem, Israel111

21

The following list includes centers, funding organizations and other resources related to

bioelectronics research; it should not be considered comprehensive.

Research centers

agency for science, technology and Research (a*staR) – Institute for Microelectronics

http://www.ime.a-star.edu.sg

arizona state University – Center for Bioelectronics and Biosensors

http://www.biodesign.asu.edu/research/research-centers/bioelectronics-and-biosensors

clemson University – Center for Bioelectronics, Biosensors and Biochips

http://www.clemson.edu/c3b

duke University – Center for Neuroengineering

http://www.duke.edu/~ch/Neuroeng/Neuro.htm

Fraunhofer Institute for biomedical engineering – Molecular Bioanalytics and Bioelectronics

http://www.ibmt.fraunhofer.de/fhg/ibmt_en/biomedical_engineering/molecular_bioanalyt-

ics_bioelectronics/index.jsp

Janelia Farm – Howard Hughes Medical Institute

http://www.hhmi.org/janelia

seoul national University – Nano-Bioelectronics & Systems Research Center

http://nanobio.snu.ac.kr

University of california-santa cruz – Integrated Bioelectronics Research

http://ibr.soe.ucsc.edu/?file=kop1.php

University of michigan – Center for Wireless Integrated Microsystems

http://www.wimserc.org

University of south california – Biomimetic MicroElectronic Systems Research Center

http://www.erc-assoc.org/factsheets/15/15-Fact%20Sheet%20Save%20as%20Webpage.htm

University of Utah – Center for Advanced Imaging Research

http://www.ucair.med.utah.edu

government programs

The Department of Energy has within its Office of Basic Energy Sciences multidisciplinary

programs that fund projects at national laboratories and universities.

http://www.science.doe.gov/Program_Offices/BES.htm

The Food and Drug Administration (FDA) has programs related to the multidisciplinary

aspects of applying bioelectronics to protecting the environment. The FDA Office of Science

appendix b: bioelectronics Research Resources

22

and Engineering Laboratories has several divisions that contribute to bioelectronics.

http://www.fda.gov/cdrh/osel/researchlabs

The National Institutes for Health (NIH) has many intramural and extramural programs

involving bioelectronics. Examples include:

National Institute for Biomedical Imaging and Bioengineering

http://www.nibib.nih.gov/Research/Intramural

http://www.nibib.nih.gov/Research/ProgramAreas

National Cancer Institute Network for Translational Research

http://proteomics.cancer.gov

National Institute of Diabetes and Digestive and Kidney Diseases

http://www2.niddk.nih.gov

National Institute of Standards and Technology (NIST) has bioelectronics projects in many

of its laboratories, such as those involved with electronics and electrical engineering, chem-

istry, physics, materials research and information technologies. Examples include:

http://www.nist.gov/pml

http://www.nist.gov/mml

http://www.nist.gov/itl

http://www.nist.gov/msel/biomaterials.cfm/

The National Science Foundation currently supports bioelectronics research in the Electron-

ics, Photonics and Device Technologies (EPDT) program.

http://www.nsf.gov/funding/pgm_summ.jsp?pims_id=13379/

books

Willner, I. and E. Katz (eds.), Bioelectronics: From Theory to Applications, Wiley-VCH, Wein-

heim, Germany, 2005.

http://www.amazon.com/Bioelectronics-Theory-Applications-Itamar Willner/dp/3527306900/

ref=sr_1_1?ie=UTF8&s=books&qid=1229293104

market Reports

SRI Consulting Business Intelligence – Next-generation technologies: Bioelectronics

http://www.sric-bi.com/Explorer/NGT-BE.shtml/

Venn Research, Inc. -- Worldwide Biosensor and Bioelectronic Market

http://www.marketresearch.com/map/prod/1343053.html

BCC Research – Biotechnology: Biosensors and Bioelectronics

http://www.bccresearch.com/report/BIO039B.html

23

agenda 2nd SRC Bioelectronics Roundtable (BERT2) Howard Hughes Medical Institute (HHMI) Janelia Farm Research Campus March 25-26, 2010

8:30 – 8:45 welcoming Remarks Kevin Moses, Janelia Farm

8:45 – 9:00 Roundtable program and goals Celia Merzbacher, SRC

9:00 – 11:30 session 1. ex Vivo systems Overview by Madoo Varma, Intel Corp. Session Moderator – Lloyd Whitman, NIST

breakout discussion

12:30 – 3:00 session 2. In Vivo systems Overview by Jack Judy, DARPA Session Moderator – William Heetderks, NIBIB

breakout discussion

3:20 – 5:50 session 3. Imaging Overview by Jonathan Murray, GE Healthcare Session Moderator – Sankar Basu, NSF

breakout discussion

6:30 – dinner/Informal networking

8:00 – 8:20 bioelectronics Research and development at a*staR Institute for microelectronics Tushar Bansal (A*STAR IME, Singapore)

8:20 – 8:30 overview of day 2 goals

8:30 – 10:00 breakout group discussions on challenges

10:00 – 10:30 session summaries

10:30 – 10:45 prioritization of Identified opportunities

11:00 – 12:15 session 4. wrap-up: summary/discussion of prioritization and next steps

12:15 adjourn

12:15 – 1:15 Lunch Tour of Janelia Farm Research Center [optional]

tHursday, marcH 25, 2010

Friday, marcH 26, 2010

appendix c: agenda for 2nd bioelectronics Roundtable meeting

24

Roundtable participants

2nd SRC Bioelectronics Roundtable (BERT2)

Howard Hughes Medical Institute (HHMI) Janelia Farm Research Campus

participant affiiation

Guillermo Arreaza-Rubin National Institute of Diabetes and Digestive and Kidney Diseases

Tsunetoshi Arikado Tokyo Electron Ltd.

Tushar Bansal A*STAR Institute of Microelectronics, Singapore

Sankar Basu National Science Foundation

Anastasiya Batrachenko Semiconductor Research Corporation

Michael Gaitan National Institute of Standards and Technology

Timothy Harris Janelia Farm/Howard Hughes Medical Institute

William Heetderks National Institute of Biomedical Imaging and Bioengineering

Daniel Herr Semiconductor Research Corporation

William Joyner Semiconductor Research Corporation

Jack Judy Defense Advanced Research Projects Agency

Sam Kavasi The Bosch Group

Maren Laughlin National Institute of Diabetes and Digestive and Kidney Diseases

Celia Merzbacher Semiconductor Research Corporation

Kevin Moses Janelia Farm/Howard Hughes Medical Institute

Jonathan Murray GE Healthcare

Steve Pollock Food & Drug Administration

Dave Seiler National Institute of Standards and Technology

Stacey Shirland Semiconductor Research Corporation

Dorel Toma Tokyo Electron Ltd.

Madoo Varma Intel Corporation

Usha Varshney National Science Foundation

Lloyd Whitman National Institute of Standards and Technology

Sufi Zafar IBM

Victor Zhirnov Semiconductor Research Corporation

appendix d: attendee list for 2nd bioelectronics Roundtable meeting

25

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redu

ctio

n by

bet

ter

biol

ogy/

imm

unol

ogy

3-y

ear

goa

l(s)

:

Con

cept

Dem

onst

ratio

n

7-y

ear

goa

l(s)

:

Com

mer

cial

Pro

toty

pe

ann

ual c

osts

:

$0.5

M

peo

ple:

5 P

hD s

tude

nts

cell InteRRogatIon platFoRmsHUman dIagnostIcs – label-FRee low

and HIgH densIty electRonIc aRRays

26

pers

oNal

iZed

med

ical

aNd

dia

GNos

tics

(con

tinue

d)

Rese

arch

Oppo

rtun

ityEs

timat

ed R

esou

rce

Requ

irem

ents

Appl

icat

ions

of I

nter

est

Rese

arch

Nee

dAd

vant

ages

Met

rics

of P

rogr

ess

dri

ver(

s):

Impr

ove

avai

labi

lity

of p

oint

-

of-c

are

diag

nost

ics

mar

ket

size

:

> n

umbe

r of

cel

l pho

nes

mar

ket

need

:

Low

-cos

t co

mpl

ete

dete

ctio

n +

fluid

ic +

rad

io +

pow

er in

tegr

atio

n

for

unde

r $

0.5

0

Det

ectio

n S

yste

m

Inte

grat

ion

with

low

-cos

t flu

idic

s

Bio

elec

tron

ics

to r

elax

the

sam

ple

prep

arat

ion

step

s/m

odul

es

Dem

onst

ratio

n in

the

fiel

d

Bio

mar

ker

disc

over

y

This

tec

hnol

ogy

can

enab

le e

arly

dia

gnos

tics

and

prev

entio

n at

poi

nt-

of-c

are

Red

uced

dev

elop

men

t/

appr

oval

cos

t fo

r

negl

ecte

d m

arke

ts

3-y

ear

goa

l(s)

:

Sys

tem

dem

onst

ratio

ns u

sing

exi

stin

g

fluid

ics

and

assa

ys

5-y

ear

goa

l(s)

:

a) C

omm

erci

al P

roto

type

b) N

ovel

ass

ay +

flui

dic

+ d

etec

tion

com

bina

tion

ann

ual c

osts

:

$1M

peo

ple:

10 P

hD s

tude

nts

dri

ver(

s):

A hi

ghly

sen

sitiv

e &

aut

omat

ed

bio-

sens

ing

plat

form

usi

ng

min

iatu

rized

fiel

d ef

fect

tra

nsis

-

tor

(FET

) de

vice

s su

ch a

s vi

rus

dete

ctio

n (e

.g. in

fluen

za, H

IV)

and

prot

ein

dete

ctio

n, in

clud

ing

canc

er s

cree

ning

mar

ket

size

:

•An

nual

influ

enza

cos

t in

US

A >

$2

00

Bill

ion

•An

nual

can

cer

cost

s in

US

A >

$1

50

Bill

ion

FET

sens

or d

esig

n &

fab

ricat

ion

optim

izat

ion

Dem

onst

ratio

n of

sen

sitiv

ity &

relia

bilit

y fo

r bi

o-se

nsin

g in

an

aque

ous

envi

ronm

ent,

incl

udin

g

eval

uatio

n of

bio

-foul

ing

Func

tiona

lizat

ion

of s

ensi

ng

surf

ace

dete

ctio

n

Cou

plin

g se

nsor

arr

ay w

ith

mic

ro-fl

uidi

cs for

sam

ple

deliv

ery

Hug

e he

alth

care

cos

t

savi

ng

Impo

rtan

t re

sear

ch t

ool

prov

idin

g ne

w in

sigh

t in

to

vira

l inf

ectio

n, c

ance

r

& o

ther

illn

esse

s, t

hus

lead

ing

to b

ette

r pr

even

-

tion

met

hods

The

sens

or t

echn

olog

y

can

also

be

appl

ied

for

dete

ctin

g op

enin

g

& c

losi

ng o

f io

n ch

anne

l

prot

eins

n

eura

l

pros

thet

ics

3-y

ear

goa

l(s)

:

Inte

grat

ion

of t

he s

enso

rs o

n

mul

ti-fu

nctio

nal,

low

pow

er p

latf

orm

for

auto

mat

ed s

ampl

e de

liver

y, d

ata

acqu

isiti

on &

tra

nsm

issi

on

5-y

ear

goa

l(s)

:

Dev

elop

men

t of

arr

ay o

f hi

ghly

relia

ble

& s

ensi

tive

labe

l fre

e se

nsor

s

TBD

label FRee bIosensIng

UsIng Fet-based sensoRsdIgItal poc dx

27

pers

oNal

iZed

med

ical

aNd

dia

GNos

tics

(con

tinue

d)

Rese

arch

Oppo

rtun

ityEs

timat

ed R

esou

rce

Requ

irem

ents

Appl

icat

ions

of I

nter

est

Rese

arch

Nee

dAd

vant

ages

Met

rics

of P

rogr

ess

dri

ver(

s):

The

deve

lopm

ent

and

adva

ncem

ent

of n

ew

tech

nolo

gies

sho

uld

be a

ccom

pani

ed w

ith

adva

nces

in m

etho

ds for

tes

ting

devi

ce

prop

ertie

s, p

erfo

rman

ce a

nd r

elia

bilit

y,

and

thei

r re

latio

nshi

p to

opt

imiz

ing

man

u-

fact

urin

g m

etho

ds.

mar

ket

need

:

Nee

ds for

tes

t m

etho

ds a

nd in

stru

men

ta-

tion

shou

ld b

e id

entifi

ed, p

riorit

ized

and

road

-map

ped.

The

deve

lopm

ent

of s

tand

ards

, cal

ibra

tion

faci

litie

s an

d st

anda

rd r

efer

ence

mat

eria

ls

take

s tim

e. S

tand

ards

org

aniz

atio

ns s

uch

as S

EMI,

ASTM

and

NIS

T, a

nd o

ther

age

n-

cies

suc

h as

NS

F, c

an w

ork

with

aca

dem

ic

and

indu

stria

l gro

ups

to id

entif

y cr

oss

cutt

ing

and

prec

ompe

titiv

e ne

eds.

Dev

elop

men

t of

new

tes

t

met

hods

Inst

rum

enta

tion

deve

lopm

ent

Det

erm

ine

need

s fo

r ca

libra

tion

faci

litie

s

Dev

ice

perf

orm

ance

tes

ting

Exam

ples

of cu

rren

t ne

eds

iden

tified

or

unde

r co

nsid

er-

atio

n by

SEM

I inc

lude

:

a) S

tand

ard

test

met

hod

for

elec

troo

smot

ic a

nd e

lect

roph

o-

retic

flow

pro

pert

ies

b) S

tand

ards

for

defi

ning

the

dete

ctor

sen

sitiv

ity a

nd r

esol

u-

tion

of s

epar

atio

ns

c) P

rope

rtie

s da

taba

se(s

), e.

g.

cond

uctiv

ity a

nd p

erm

ittiv

ity v

s.

freq

uenc

y.

Enab

les

the

accu

rate

com

pari-

son

of p

erfo

rman

ce b

etw

een

devi

ce t

echn

olog

ies

and

rese

arch

gro

ups.

This

kno

wle

dge

will

be

need

ed

for

the

coor

dina

tion

and

deve

l-

opm

ent

of t

est

and

cert

ifica

tion

prot

ocol

s w

ith fed

eral

reg

ula-

tory

age

ncie

s, s

uch

as F

DA,

etc

.

Early

aw

aren

ess

of s

tand

ards

and

calib

ratio

n re

quire

men

ts s

o

that

indu

stria

l nee

ds a

re m

et in

adva

nce.

3-y

ear

goa

l(s)

:

Iden

tifica

tion

of m

etro

logy

need

s

Prio

ritiz

atio

n of

nee

ds

Gui

danc

e fo

r fe

dera

l age

n-

cies

, suc

h as

NIS

T, f

or

plan

ning

wor

k, f

acili

ties

and

exte

rnal

inve

stm

ent

Tech

nolo

gy a

nd m

etro

logy

road

-map

ping

Dev

elop

men

t of

sta

ndar

ds

to s

uppo

rt c

ross

cut

ting

and/

or p

reco

mpe

titiv

e

mea

sure

men

t ne

eds

TBD

dri

ver(

s):

Labe

l-fre

e, r

eal-t

ime,

in v

ivo

or

in v

itro,

bro

ad-s

pect

rum

det

ectio

n

mar

ket

size

:

Vast

app

licat

ion

spac

e in

bio

mar

kers

, IVD

,

met

abol

omic

s, p

rote

omic

s, g

enom

ics

mar

ket

need

:

An in

tegr

ated

chi

p-ba

sed

syst

em c

apab

le

of m

onito

ring

stoc

hast

ic b

ind

and

un-

bind

ing

even

ts a

nd p

rovi

ding

the

sig

nal

proc

essi

ng t

o tr

ansl

ate

the

bind

ing

sign

atur

es.

Sen

sing

sur

face

pot

entia

l

chan

ges

with

sin

gle-

mol

ecul

e

reso

lutio

n

Bio

info

rmat

ics

to in

terp

ret

stoc

hast

ic s

igna

ls

Bio

com

patib

le p

acka

ging

to

prev

ent

bio-

enca

psul

atio

n of

the

devi

ce

Wou

ld c

reat

e a

tota

lly n

ew a

p-

proa

ch t

o bi

osen

sing

, allo

win

g

the

sam

e sy

stem

s to

be

used

in v

itro

and

in v

ivo.

With

few

reag

ents

and

bro

ad-s

pect

rum

capa

bilit

ies,

may

be

low

eno

ugh

cost

for

dev

elop

ing

coun

trie

s

ben

efits

/ad

vant

ages

ove

r cu

r-

rent

cap

abili

ties

or

tech

nolo

gy:

This

tec

hnol

ogy

wou

ld e

limin

ate

the

need

for

mic

roar

rays

and

mul

ti-st

ep la

belin

g as

says

.

3-y

ear

goa

l(s)

:

Dem

onst

rate

mul

tiple

xed,

stoc

hast

ic s

ensi

ng o

f 8

anal

ytes

in b

iolo

cial

mat

rices

with

off

-chi

p si

gnal

proc

essi

ng.

5-y

ears

goa

l(s)

:

Dem

onst

rate

mul

tipex

ed

stoc

hast

ic s

ensi

ng o

f 64

anal

ytes

in b

iolo

gica

l mat

ri-

ces

with

on-

chip

sig

nal

proc

essi

ng a

nd 1

(on

e)

mon

th o

pera

tion

in v

ivo.

est.

ann

ual c

osts

:

~$5M

/yea

r;

peo

ple:

10-1

5

Faci

litie

s:

Inte

rdis

cipl

inar

y

team

s w

ith a

cces

s

to C

MO

S, n

ano-

elec

tron

ics

fabr

icat

ion

and

clin

ical

tes

t

faci

litie

s.

stocHastIc sensIngcHaRacteRIzatIon metHods FoR

bIoelectRonIc deVIces

28

impl

aNta

Ble

devi

ces

aNd

pros

tHet

ics

Rese

arch

Oppo

rtun

ityEs

timat

ed R

esou

rce

Requ

irem

ents

Appl

icat

ions

of I

nter

est

Rese

arch

Nee

dAd

vant

ages

Met

rics

of P

rogr

ess

dri

ver(

s):

Hig

h pe

rfor

man

ce, r

obus

t

and

relia

ble

pros

thet

ics

for

ampu

tees

mar

ket

need

:

Reg

ain

func

tion

need

ed t

o

retu

rn t

o du

ty, m

aint

ain

qual

ity

of li

fe (ro

tatio

n/po

st s

ervi

ce)

Cur

rent

ly lo

ng-te

rm (ye

ars)

rel

iabl

e

neur

al-e

lect

roni

c in

terf

ace

or B

MI

does

not

exi

st. Ev

en a

one

-bit

switc

h

has

yet

to b

e co

ntro

lled

relia

bly.

Appl

icat

ions

tha

t ca

ll fo

r hi

gh-

prec

isio

n/sp

eed

cont

rol o

f m

any-

degr

ee-o

f-fre

edom

sys

tem

s ar

e

pres

ently

out

of re

ach.

Rel

iabi

lity

cha

lleng

e 1: Ph

ysic

al

neur

al-e

lect

roni

c in

terf

ace.

Sig

nal-t

o-

nois

e ra

tio o

f si

ngle

-uni

t po

tent

ials

typi

cally

dec

ays

to z

ero

in <

1 t

o 2

year

s, o

ften

muc

h so

oner

.

Rel

iabi

lity

cha

lleng

e 2: Fa

st a

nd

corr

ect

oper

atio

n (>

>99%

) re

quire

d;

patie

nt a

ccep

tanc

e of

pro

sthe

ses.

Hig

her-P

erfo

rman

ce a

nd

Rel

iabl

e B

rain

-Con

trol

led

Neu

ral P

rost

hetic

s

3-y

ear

goa

l(s)

:

Rel

iabl

e an

d ro

bust

con

trol

of

one-

bit

switc

hes

for

neur

al-e

lect

roni

c in

terf

ace

appl

icat

ions

10-y

ear

goa

l(s)

:

A hi

gh p

erfo

rman

ce, r

obus

t, an

d

relia

ble

bio-

abio

tic in

terf

ace

A hi

gh-p

erfo

rman

ce,

robu

st a

nd r

elia

ble

bio-

abio

tic in

terf

ace

$3M

– $

13M

peo

ple,

tim

e an

d

faci

litie

s: T

BD

dri

ver(

s):

Impr

ove

the

heal

th a

nd q

ualit

y

of li

fe o

f pe

ople

with

car

dio-

vasc

ular

or

perip

hera

l vas

cula

r

dise

ase.

mar

ket

size

:

As m

any

as 1

bill

ion

peop

le

mar

ket

need

:

An a

utom

ated

wire

less

blo

od

flow

mea

surin

g sy

stem

tha

t

prov

ides

a s

impl

e re

al-ti

me

hand

-hel

d m

onito

ring

devi

ce

for

the

patie

nt

Nan

o w

ire s

enso

rs, w

irele

ss

pow

erin

g an

d m

easu

rem

ent,

and

man

agem

ent

Sof

twar

e an

d sy

stem

con

trol

algo

rithm

s

Impl

anta

ble

devi

ce o

n to

the

vasc

ular

sys

tem

or

graf

t

Impa

ct, i

f su

cces

sful

:

This

tec

hnol

ogy

wou

ld

bene

fit t

he li

ves

of

mill

ions

of pe

ople

with

card

iova

scul

ar o

r

perip

hera

l-vas

cula

r

dise

ase.

This

tec

hnol

ogy

coul

d

impr

ove

the

qual

ity o

f lif

e

and

prev

ent

com

plic

ated

surg

ery

and

asso

ciat

ed

impa

cts

of p

ain

and

cost

.

3-y

ear

goa

l(s)

:

Dem

onst

rate

the

fea

sibi

lity

of

an im

plan

tabl

e w

irele

ss b

lood

flow

sys

tem

5-y

ear

goa

l(s)

:

Dem

onst

rate

the

fea

sibi

lity

of a

n

impl

anta

ble,

wire

less

mul

ti-pa

ram

eter

card

iac

mea

surin

g sy

stem

with

bio

-

com

patib

le p

acka

ging

10-y

ear

goa

l(s)

:

Suc

cess

ful d

emon

stra

tion

of t

he

wire

less

car

diac

mon

itorin

g sy

stem

in h

uman

bod

ies

ann

ual c

ost:

~$700K

/yea

r;

peo

ple:

3-4

Fac

ulty

Faci

litie

s:

Inte

rdis

cipl

inar

y

team

s w

ith a

cces

s

to n

ano-

elec

tron

ics

& M

EMS

fab

ricat

ion

and

clin

ical

tes

t

faci

litie

s

Implantable caRdIac

blood Flow monItoR

HIgHeR-peRFoRmance and RelIable

bRaIn-contRolled neURal pRostHetIcs

29

impl

aNta

Ble

devi

ces

aNd

pros

tHet

ics

(con

tinue

d)

Rese

arch

Oppo

rtun

ityEs

timat

ed R

esou

rce

Requ

irem

ents

Appl

icat

ions

of I

nter

est

Rese

arch

Nee

dAd

vant

ages

Met

rics

of P

rogr

ess

Sem

icon

duct

or-b

ased

quan

titat

ive

diag

nost

ics

of

mul

tiple

bio

mar

kers

dri

ver(

s):

Cur

rent

ly r

esea

rch

is u

nder

way

to d

etec

t bi

omar

kers

and

unde

rsta

nd t

he b

iolo

gica

l

path

way

s as

soci

ated

with

dise

ases

and

the

ir bi

omar

k-

ers.

Thi

s w

ill s

et t

he s

tage

for

devi

ces

that

will

qua

ntita

tivel

y

mon

itor

mul

tiple

bio

mar

kers

over

tim

e in

ord

er t

o de

tect

chro

nic

dise

ases

at

an e

arly

stag

e. T

hese

tes

ts w

ill b

e

done

at

a do

ctor

’s o

ffice

or

at

hom

e. T

he d

evic

es h

ave

to b

e

easy

to

use

and

robu

st.

mar

ket

size

:

Sev

eral

bill

ion

Sem

icon

duct

or t

echn

olog

y fo

r

incr

easi

ng s

elec

tivity

and

sen

sitiv

-

ity o

f bi

omar

ker

dete

ctio

n by

usi

ng

low

-cos

t ch

emis

try

— o

vera

ll co

st is

still

low

; se

mic

ondu

ctor

tec

hnol

ogy

is e

nabl

er.

To a

chie

ve t

his,

res

earc

h at

the

inte

r-

face

of bi

oche

mis

try

and

sem

icon

-

duct

or t

echn

olog

y ha

s to

be

done

:

a) u

nder

stan

ding

inte

ract

ion

betw

een

sem

icon

duct

or d

evic

e

and

bioc

hem

istr

y,

b) c

reat

ing

clos

ed c

ontr

ol lo

ops

arou

nd t

he in

terf

ace

betw

een

bio-

chem

istr

y an

d se

mic

ondu

ctor

dev

ice.

This

app

roac

h w

ill le

ad

to a

ffor

dabl

e an

d re

peat

-

able

tec

hnol

ogy

for

early

det

ectio

n of

chr

onic

dise

ase

and,

the

refo

re,

will

low

er t

he o

vera

ll

heal

thca

re c

ost

and

incr

ease

qua

lity

of li

fe.

3-y

ear

goa

l(s)

:

a) In

terf

ace

betw

een

sem

icon

duct

ors

and

bioc

hem

istr

y is

bet

ter

unde

rsto

od

b) P

roto

type

s de

velo

ped

and

dem

on-

stra

ted

for

life

scie

nces

5-y

ear

goa

l(s)

:

Prot

otyp

es in

clin

ical

tria

l

10-y

ear

goa

l(s)

:

Prod

ucts

on

the

mar

ket

ann

ual c

osts

:

$2M

peo

ple:

15 P

hD s

tude

nts

Faci

litie

s:

Fund

ed c

ore

faci

litie

s,

surf

ace

chem

istr

y

serv

ices

dri

ver(

s):

Extr

eme

Cap

sule

End

osco

py

mar

ket

size

:

Pote

ntia

l for

wid

espr

ead

use

mar

ket

need

:

Exam

ples

of un

met

bio

/

med

ical

nee

d: e

arly

det

ectio

n

of c

ance

r; a

ctiv

e im

agin

g at

the

leve

l of ce

ll ph

ysio

logy

Ultr

a-co

mpa

ct e

nerg

y so

urce

s

Com

mun

icat

ion

with

an

exte

rnal

stat

ion

Mic

ro-s

cale

sys

tem

ass

embl

y

and

pack

agin

g

Impa

ct, i

f su

cces

sful

:

In v

ivo

diag

nost

ics

and

ther

apeu

tics

at t

he le

vel

of in

divi

dual

cel

ls

adv

anta

ges:

a) N

on-in

vasi

ve,

real

-tim

e, h

igh-

reso

lutio

n,

high

-sel

ectiv

ity

b) S

yner

gist

ic w

ith

curr

ent

sem

icon

duct

or

tren

ds (sc

alin

g, fun

c-

tiona

l div

ersi

ficat

ion)

3-y

ear

goa

l(s)

:

Sub

-mm

siz

e en

ergy

sou

rce

5-y

ear

goa

l(s)

:

Sub

syst

ems

dem

onst

rate

d (p

ower

supp

ly, m

icro

cont

rolle

r, se

nsor

s,

com

mun

icat

ion)

10-t

o-12-y

ear

goa

l(s)

:

Prot

otyp

ed m

icro

n-sc

ale

syst

em

dem

onst

rate

d

ann

ual c

osts

:

~$4M

/yea

r

peo

ple:

~10

Faci

litie

s:

Che

mis

try

and

engi

neer

ing

team

s

with

acc

ess

to

rele

vant

ope

ratio

nal

envi

ronm

ents

nanomoRpHIc cellsmUltIplexed bIomaRkeR detectIon

30

impl

aNta

Ble

devi

ces

aNd

pros

tHet

ics

(con

tinue

d)

Rese

arch

Oppo

rtun

ityEs

timat

ed R

esou

rce

Requ

irem

ents

Appl

icat

ions

of I

nter

est

Rese

arch

Nee

dAd

vant

ages

Met

rics

of P

rogr

ess

dri

ver(

s):

Enha

nce

early

iden

tifica

tion

of c

ance

r an

d ot

her

dise

ase

mar

ket

size

:

50

0 m

illio

n pe

ople

wor

ldw

ide

mar

ket

need

:

Can

cer

dete

ctio

n ch

ip n

ot

only

with

hig

h se

nsiti

vity

but

also

with

low

cos

t. In

add

ition

,

shor

t cy

cle

time

is e

ssen

tial

for

mon

itorin

g an

d sc

reen

ing.

Para

sitic

inte

rfac

e pa

ram

eter

s

(R;C

;H) be

twee

n el

ectr

onic

s, s

en-

sors

and

ant

ibod

ies

can

be a

“sh

ow

stop

per”

in in

vest

igat

ion

by r

educ

ing

dram

atic

sen

sitiv

ity.

Iden

tify

sens

or r

espo

nses

to

spec

ific

antib

ody

Who

le b

lood

ana

lysi

s w

ith n

o

pret

reat

men

ts

To d

evel

op in

terf

ace

betw

een

sens

ors

and

elec

tron

ics

Dev

elop

men

t of

dat

abas

e ba

sed

on r

ace,

reg

ion

and

natio

n to

diag

nose

pre

cise

ly.

Impa

ct, i

f su

cces

sful

:

Hug

e am

ount

of pe

ople

wou

ld h

ave

canc

er

chec

k ev

ery

year

. C

ance

r

coul

d be

det

ecte

d at

early

sta

ge.

Low

-cos

t di

agno

ses,

rapi

d an

d hi

gh-s

ensi

tivity

,

early

-sta

ge d

etec

tion.

3-y

ear

goa

l(s)

:

Iden

tify

sens

ors

resp

onsi

ble

to

spec

ific

antib

odie

s

5-y

ear

goa

l(s)

:

Inte

rfac

e be

twee

n el

ectr

onic

s an

d

hum

an b

ody

TBD

dri

ver(

s):

An a

rtifi

cial

pan

crea

s th

at

mon

itors

and

con

trol

s gl

ucos

e

in t

he b

lood

, thu

s pr

ovid

ing

diab

etic

car

e

mar

ket

size

:

1/3

hea

lthca

re c

osts

att

rib-

uted

to

diab

etic

car

e; g

row

th

in t

he n

umbe

r of

peo

ple

with

diab

etes

is e

xpec

ted

to r

each

25

0 m

illio

n by

the

yea

r 2

02

5.

Dev

elop

non

-inva

sive

glu

cose

sen

sor

that

pro

vide

s re

al-ti

me

mea

sure

of

bloo

d su

gar

Dev

elop

men

t of

insu

lin p

umps

& s

enso

rs

Bas

ed o

n hu

man

phy

siol

ogy, d

evel

-

opm

ent

of a

lgor

ithm

s th

at p

rovi

de

accu

rate

clo

se-lo

op a

utom

atio

n

betw

een

sens

ors

& d

eliv

ery

pum

ps

Red

uced

hea

lthca

re

cost

s

Impr

oved

dia

betic

car

e

Can

be

inte

grat

ed w

ith

bloo

d pr

essu

re a

nd

tem

pera

ture

sen

sors

for

furt

her

impr

ovem

ent

Prov

ide

new

sci

en-

tific

unde

rsta

ndin

g of

diab

etes

to

food

inta

ke

and

lifes

tyle

s –

a be

tter

met

hod(

s) for

pre

vent

ion

3-y

ear

goa

l(s)

:

Dev

elop

men

t of

inte

grat

ed c

hip

cons

istin

g of

sen

sor

and

pum

ps

7-y

ear

goa

l(s)

:

Dev

elop

men

t of

alg

orith

ms

for

clos

e-lo

op a

utom

atio

n

TBD

aRtIFIcIal pancReasbIosensoRs

31

dri

ver(

s):

Enha

nce

early

iden

tifica

tion

of c

ance

r an

d ot

her

dise

ase

mar

ket

size

:

50

0 m

illio

n pe

ople

wor

ldw

ide

mar

ket

need

:

Can

cer

dete

ctio

n ch

ip n

ot

only

with

hig

h se

nsiti

vity

but

also

with

low

cos

t. In

add

ition

,

shor

t cy

cle

time

is e

ssen

tial

for

mon

itorin

g an

d sc

reen

ing.

Para

sitic

inte

rfac

e pa

ram

eter

s

(R;C

;H) be

twee

n el

ectr

onic

s, s

en-

sors

and

ant

ibod

ies

can

be a

“sh

ow

stop

per”

in in

vest

igat

ion

by r

educ

ing

dram

atic

sen

sitiv

ity.

Iden

tify

sens

or r

espo

nses

to

spec

ific

antib

ody

Who

le b

lood

ana

lysi

s w

ith n

o

pret

reat

men

ts

To d

evel

op in

terf

ace

betw

een

sens

ors

and

elec

tron

ics

Dev

elop

men

t of

dat

abas

e ba

sed

on r

ace,

reg

ion

and

natio

n to

diag

nose

pre

cise

ly.

Impa

ct, i

f su

cces

sful

:

Hug

e am

ount

of pe

ople

wou

ld h

ave

canc

er

chec

k ev

ery

year

. C

ance

r

coul

d be

det

ecte

d at

early

sta

ge.

Low

-cos

t di

agno

ses,

rapi

d an

d hi

gh-s

ensi

tivity

,

early

-sta

ge d

etec

tion.

3-y

ear

goa

l(s)

:

Iden

tify

sens

ors

resp

onsi

ble

to

spec

ific

antib

odie

s

5-y

ear

goa

l(s)

:

Inte

rfac

e be

twee

n el

ectr

onic

s an

d

hum

an b

ody

TBD

dri

ver(

s):

An a

rtifi

cial

pan

crea

s th

at

mon

itors

and

con

trol

s gl

ucos

e

in t

he b

lood

, thu

s pr

ovid

ing

diab

etic

car

e

mar

ket

size

:

1/3

hea

lthca

re c

osts

att

rib-

uted

to

diab

etic

car

e; g

row

th

in t

he n

umbe

r of

peo

ple

with

diab

etes

is e

xpec

ted

to r

each

25

0 m

illio

n by

the

yea

r 2

02

5.

Dev

elop

non

-inva

sive

glu

cose

sen

sor

that

pro

vide

s re

al-ti

me

mea

sure

of

bloo

d su

gar

Dev

elop

men

t of

insu

lin p

umps

& s

enso

rs

Bas

ed o

n hu

man

phy

siol

ogy, d

evel

-

opm

ent

of a

lgor

ithm

s th

at p

rovi

de

accu

rate

clo

se-lo

op a

utom

atio

n

betw

een

sens

ors

& d

eliv

ery

pum

ps

Red

uced

hea

lthca

re

cost

s

Impr

oved

dia

betic

car

e

Can

be

inte

grat

ed w

ith

bloo

d pr

essu

re a

nd

tem

pera

ture

sen

sors

for

furt

her

impr

ovem

ent

Prov

ide

new

sci

en-

tific

unde

rsta

ndin

g of

diab

etes

to

food

inta

ke

and

lifes

tyle

s –

a be

tter

met

hod(

s) for

pre

vent

ion

3-y

ear

goa

l(s)

:

Dev

elop

men

t of

inte

grat

ed c

hip

cons

istin

g of

sen

sor

and

pum

ps

7-y

ear

goa

l(s)

:

Dev

elop

men

t of

alg

orith

ms

for

clos

e-lo

op a

utom

atio

n

TBD

impl

aNta

Ble

devi

ces

aNd

pros

tHet

ics

(con

tinue

d)

Rese

arch

Oppo

rtun

ityEs

timat

ed R

esou

rce

Requ

irem

ents

Appl

icat

ions

of I

nter

est

Rese

arch

Nee

dAd

vant

ages

Met

rics

of P

rogr

ess

dri

ver(

s):

Sen

sing

and

con

trol

ling

activ

ity o

f ne

uron

s

in a

wak

e, fre

ely

mov

ing

rese

arch

mic

e.

mar

ket

size

:

25

0-5

00

res

earc

h gr

oups

wor

ldw

ide,

~$

50

-15

0K

per

gro

up p

er y

ear

annu

al

spen

ding

in t

he a

rea.

Som

e lo

ng-te

rm

over

lap

with

hum

an c

linic

al b

rain

impl

ants

.

mar

ket

need

:

Con

trol

ling

and

mon

itorin

g ac

tivity

of

indi

vidu

al n

euro

ns in

gen

etic

ally

mod

ified

mic

e. S

elec

ted

neur

ons

are

mad

e op

tical

ly

sens

itive

so

that

neu

ron

firin

g ca

n be

indu

ced

with

ligh

t.

5-1

0-m

m lo

ng lo

w lo

ss (0.5

dB

)

mul

timod

e op

tical

wav

egui

des

inte

grat

ed o

nto

~20-u

m t

hick

,

60-u

m w

ide

prob

es, t

o be

inse

rted

into

the

bra

in o

f m

ice

5-1

0-m

m lo

ng lo

w lo

ss (0.5

dB

)

mul

timod

e op

tical

wav

egui

des

inte

grat

ed o

nto

~20-u

m t

hick

,

60-u

m w

ide

prob

es, t

o be

inse

rted

into

the

bra

in o

f m

ice

32-6

4 5

-10-u

m d

iam

eter

met

al

site

s in

tegr

ated

into

thi

s sa

me

devi

ce, w

ith c

ondu

ctor

s in

to t

he

head

-mou

nted

am

plifi

ers

Cur

rent

fibe

r-cou

pled

dev

ices

caus

e co

nsid

erab

le a

nim

al

pert

urba

tion.

Wire

less

(ba

tter

y

pow

ered

) or

thi

n fle

xibl

e po

w-

ered

dev

ices

wou

ld b

e m

uch

pref

erre

d.

Flex

ibly

pro

gram

med

opt

ical

exci

tatio

n an

d el

ectr

ical

det

ec-

tion

with

min

imal

per

turb

atio

n

of a

nim

al b

ehav

ior.

Flex

ible

mod

ular

des

ign

and

fabr

icat

ion

plat

form

1-y

ear

goa

l(s)

:

a) L

ow-lo

ss p

olym

er p

lana

r

wav

egui

de f

abric

atio

n

b) L

ow-lo

ss c

oupl

ing

of a

n

inte

grat

ed e

mitt

er

2-y

ear

goa

l(s)

:

a) S

witc

habl

e em

itter

col

or

at c

oupl

ing,

b) S

witc

habl

e em

issi

on s

ite

on p

robe

3-y

ear

goa

l(s)

:

Proj

ect

com

plet

ion

a) In

tegr

atio

n of

mul

ticol

or

sour

ces

with

ele

ctric

al p

robe

,

b) M

ulti-

shan

k ve

rsio

ns

fabr

icat

ed

~$0.5

-1/y

r, 2

FTE

plus

MEM

S

fabr

icat

ion

cost

thro

ugh

seve

ral

cycl

es o

f de

sign

and

test

dri

ver(

s):

Sen

sing

act

ivity

of la

rge

num

bers

of

neur

ons

in m

ouse

and

rat

bra

ins

to u

nder

-

stan

d ba

sic

brai

n fu

nctio

n.

mar

ket

size

:

50

0-1

00

0 r

esea

rch

grou

ps w

orld

wid

e,

~$

50

-15

0K

per

gro

up p

er y

ear

annu

al

spen

ding

. S

ubst

antia

l lon

g-te

rm o

verla

p

with

hum

an c

linic

al b

rain

impl

ants

.

mar

ket

need

: M

onito

ring

activ

ity o

f

indi

vidu

al n

euro

ns is

a c

omm

on a

nd b

asic

part

of ne

urob

iolo

gy r

esea

rch.

Cur

rent

de-

vice

s co

mpa

tible

with

mic

e an

d ra

ts h

ave

at m

ost

64

sen

sing

site

s. S

yste

ms

with

thou

sand

s of

site

s ar

e ne

eded

.

Bra

in im

mer

sed

high

sen

sor

site

“sh

anks

” w

ith m

ultip

lex-

ing

and

ampl

ifica

tion

on s

hank

and/

or m

ultil

ayer

met

alliz

atio

n

with

just

abo

ve b

rain

pro

gram

-

mab

le m

ultip

lexi

ng

Very

ligh

twei

ght

head

-mou

nted

mul

tiple

xing

and

am

plify

ing

elec

tron

ics

Far

mor

e co

mpl

ete

data

set

s

reso

lvin

g cu

rren

t am

bigu

ities

of

activ

e ne

uron

cou

nt

Abili

ty t

o m

onito

r m

ultip

le b

rain

regi

ons

at t

he s

ame

time

Res

olut

ion

of c

lose

ly s

pace

d

neur

ons

3-y

ear

goa

l(s)

:

a) In

tegr

ated

sin

gle

shan

k

devi

ces

with

500-1

000 a

d-

dres

sabl

e si

tes

per

shan

k,

b) H

ead-

mou

nted

ele

ctro

n-

ics

to m

ultip

lex

up t

o 5000

sign

als

5-y

ear

goa

l(s)

:

Proj

ect

com

plet

ion:

5

prob

es, 1

0 s

hank

s ea

ch,

500-1

000 s

enso

r si

tes

per

shan

k

est.

ann

ual c

osts

:

~$5M

/yea

r;

peo

ple:

10-1

5

Faci

litie

s:

Inte

rdis

cipl

inar

y

team

s w

ith a

cces

s

to C

MO

S, n

ano-

elec

tron

ics

fabr

icat

ion

and

clin

ical

tes

t fa

cili-

ties.

neURopHysIology pRobesIntegRated optIcal & electRIcal

neURopHysIology pRobes

32

impl

aNta

Ble

devi

ces

aNd

pros

tHet

ics

(con

tinue

d)

Rese

arch

Oppo

rtun

ityEs

timat

ed R

esou

rce

Requ

irem

ents

Appl

icat

ions

of I

nter

est

Rese

arch

Nee

dAd

vant

ages

Met

rics

of P

rogr

ess

dri

ver(

s):

Adul

ts h

ave

brow

n ad

ipos

e tis

sue

(hB

AT)

whi

ch b

urns

cal

orie

s; a

ctiv

atin

g m

olec

ules

may

be

good

obe

sity

dru

gs.

mar

ket

size

:

Obe

sity

/ove

rwei

ght

affe

cts

>2

/3 o

f

Amer

ican

s, c

reat

ing

high

hea

lth c

osts

mar

ket

need

:

A ch

eap,

rel

iabl

e, q

uant

itativ

e, s

afe

way

to m

onito

r hB

AT m

ass/

activ

ity w

ould

hel

p

iden

tify

peop

le t

hat

wou

ld b

enefi

t fr

om

ther

apie

s ai

med

at

activ

atin

g it.

Nov

el t

issu

e on

ly r

ecen

tly

foun

d in

nec

k, b

elow

cla

vicl

es,

alon

g sp

ine

in le

an, y

oung

adul

t hu

man

s.

Not

cle

ar if

eld

erly,

obe

se

have

hB

AT

Activ

ated

by

cold

Few

non

-inva

sive

app

roac

hes

to

mea

surin

g m

ass

and

func

tion

of t

his

tissu

e ex

ist.

adv

anta

ges

incl

ude:

a) Id

entif

y co

nditi

ons

that

activ

ate

hBAT

,

b) M

easu

re c

ontr

ibut

ion

of

hBAT

to

ener

gy b

alan

ce/

prot

ectio

n fr

om o

besi

ty,

c) Im

prov

ed e

ndpo

ints

for

obes

ity c

linic

al t

rials

d) 1

8F-

Deo

xygl

ucos

e PE

T is

only

way

to

mon

itor

(exp

ensi

ve,

radi

atio

n ex

posu

re, n

onsp

ecifi

c)

1-t

o-5-y

ear

goa

l(s)

:

a) D

etec

t hB

AT m

ass

& a

ctiv

ity

b) T

est

in a

nim

als

and

peop

le

5-t

o-10-y

ear

goa

l(s)

:

a) D

eter

min

e hB

AT

prev

alen

ce in

pop

ulat

ion

b) S

tudy

larg

e cl

inic

al

popu

latio

ns t

o pr

ove

robu

stne

ss

c) U

se in

clin

ical

tria

ls

of o

besi

ty d

rugs

ann

ual c

osts

:

~1M

/yea

r fo

r

5 y

ears

.

Nee

d in

terd

is-

cipl

inar

y te

ams

(tec

hnic

al a

nd

bio/

med

ical

).

app

licat

ion

dri

ver:

Extr

eme

Cap

sule

End

osco

py

mar

ket

size

:

Pote

ntia

l for

wid

espr

ead

use

mar

ket

need

s:

Exam

ples

of un

met

bio

med

ical

nee

ds a

re

early

det

ectio

n of

can

cer;

act

ive

imag

ing

at t

he le

vel o

f ce

ll ph

ysio

logy

Ultr

a-co

mpa

ct e

nerg

y so

urce

s.

Com

mun

icat

ion

with

an

exte

r-

nal s

tatio

n.

Mic

ro-s

cale

sys

tem

ass

embl

y

and

pack

agin

g.

a) In

viv

o di

agno

stic

s an

d

ther

apeu

tics

at t

he le

vel o

f

indi

vidu

al c

ells

b) N

on-in

vasi

ve, r

eal-t

ime,

high

-reso

lutio

n, h

igh-

sele

ctiv

ity

c) S

yner

gist

ic w

ith c

urre

nt

sem

icon

duct

or t

rend

s (s

calin

g,

func

tiona

l div

ersi

ficat

ion)

3-y

ear

goa

l(s)

:

Sub

-mm

siz

e en

ergy

sou

rce

6-y

ear

goa

l(s)

:

Sub

syst

ems

dem

onst

rate

d (p

ower

supp

ly, m

icro

cont

rolle

r,

sens

ors,

com

mun

icat

ion)

12-y

ear

goa

l(s)

:

Prot

otyp

ed m

icro

n-sc

ale

syst

em d

emon

stra

ted

ann

ual c

ost:

~$4M

/yea

r;

peo

ple:

~10 F

acul

ty

Faci

litie

s:

Prim

arily

phy

sics

,

mat

eria

ls s

cien

ce,

chem

istr

y &

engi

neer

ing

team

s

with

acc

ess

to

rele

vant

ope

ratio

nal

envi

ronm

ents

.

nanomoRpHIc cellHUman bRown adIpose

tIssUe detectIon

33

med

ical

imaG

iNG

Rese

arch

Oppo

rtun

ityEs

timat

ed R

esou

rce

Requ

irem

ents

Appl

icat

ions

of I

nter

est

Rese

arch

Nee

dAd

vant

ages

Met

rics

of P

rogr

ess

dri

ver(

s):

Agin

g de

mog

raph

ics;

pro

duct

ivity

, i.e

., si

mul

tane

ous

dise

ase

asse

ssm

ent/

prev

entio

n/tr

eatm

ent,

acce

ss,

qual

ity, a

nd c

ost;

and

inte

grat

ed, a

cces

sibl

e,

pers

onal

ized

and

act

iona

ble

info

rmat

ion

mar

ket

size

/ne

ed:

Diff

eren

tiate

BPH

& c

hron

ic p

rost

atiti

s fr

om c

ance

r –

avoi

d bi

opsi

es in

the

se p

atie

nts.

Gui

de fr

om w

here

in the

pro

stat

e to

tak

e th

e sa

mpl

e –

usef

ul in

all

patie

nts.

If p

atie

nts

have

a p

revi

ous

nega

tive

biop

sy b

ut s

till h

igh

clin

ical

sus

pici

on t

hey

coul

d ge

t a

13

C s

can

inst

ead

of a

new

bio

psy.

sta

ging

: Lo

caliz

e w

here

and

the

siz

e of

the

pro

stat

e

the

inde

x tu

mor

is (in

dex

tum

or is

the

larg

est

lesi

on

with

the

hig

hest

Gle

ason

sco

re),

dete

rmin

e sp

read

outs

ide

pros

tatic

cap

sule

and

invo

lvem

ent

of o

ther

stru

ctur

es

sci

enti

fic p

robl

ems

and

barr

iers

:

Incr

easi

ng t

he s

ensi

tiv-

ity o

f M

R t

hrou

gh 1

3C

labe

ling

of e

ndog

enou

s

com

poun

ds t

hat

are

hype

rpol

ariz

ed w

ithin

the

MR

I dep

artm

ent.

I.V

inje

ctio

n of

the

age

nt

and

imag

ing

of s

ever

al

met

abol

ic p

rodu

ct

Impa

ct:

Sta

y he

alth

ier

long

er b

y

enab

ling

earli

er p

redi

c-

tion,

dia

gnos

is, t

reat

-

men

t an

d m

onito

ring.

ben

efits

/ad

vant

ages

:

Sig

nific

antly

fas

ter

exam

tha

n cu

rren

t

test

s us

ing

MR

Mea

sure

bio

chem

ical

“fing

erpr

int”

of tis

sue

for

earli

er d

iagn

osis

,

impr

oved

sta

ging

and

influ

ence

tre

atm

ent

deci

sion

s st

artin

g w

/

pros

tate

can

cer.

5-y

ear

goa

l(s)

:

Met

abol

ic M

R w

ith H

yper

pola

rized

1

3C

ann

ual c

ost:

$1B

ove

r 5 y

ears

acro

ss 3

are

as,

i.e.

CT, X

-ray, a

nd

MR

peo

ple,

tim

e

and

faci

litie

s:

TBD

dri

ver(

s):

Enha

nce

abili

ty o

f cl

inic

ians

to

quic

kly

perf

orm

dia

g-

nosi

s an

d re

ach

trea

tmen

t de

cisi

ons

mar

ket

size

:

This

tec

hnol

ogy

wou

ld b

enefi

t th

e liv

es o

f m

illio

ns

of p

eopl

e.

mar

ket

need

:

An a

ccur

ate,

hig

hly-

mob

ile a

nd s

afe

imag

ing

syst

em

that

will

sol

ve m

any

diag

nost

ic p

robl

ems

easi

ly

solv

ed b

y im

agin

g is

nee

ded.

Ener

gy-e

ffici

ent

ultr

a-

soni

c tr

ansd

uctio

n

mec

hani

sm a

nd s

igna

l

dete

ctio

n

Sof

twar

e an

d

imag

ing

algo

rithm

s

Ultr

a-lo

w-p

ower

mix

ed-

sign

al in

tegr

ated

circ

uits

(mill

iwat

t)

This

tec

hnol

ogy

wou

ld

redu

ce t

he c

ost

of

and

expa

nd a

cces

s

to u

ltras

onic

imag

ing

espe

cial

ly in

the

dev

el-

opin

g w

orld

It w

ould

als

o en

able

on-s

ite d

iagn

ostic

s

and

quic

k tr

eatm

ent

deci

sion

s in

em

er-

genc

y si

tuat

ions

cos

t

effe

ctiv

ely.

3-y

ear

goa

l(s)

:

Dem

onst

rate

feas

ibili

ty o

f

a la

ptop

-siz

ed 3

D u

ltras

onic

imag

er

capa

ble

of thr

ee h

ours

of c

ontin

u-

ous

batt

ery-

pow

ered

ope

ratio

n

5-y

ear

goa

l(s)

:

Dem

onst

rate

fea

sibi

lity

of a

palm

-siz

ed 3

D u

ltras

onic

imag

er

capa

ble

of 8

hou

rs o

f co

ntin

uous

batt

ery-

pow

ered

ope

ratio

n

10-y

ear

goa

l(s)

:

Dem

onst

rate

fea

sibi

lity

of a

palm

-siz

ed 3

D u

ltras

onic

imag

er

capa

ble

of 2

day

s of

con

tinuo

us

batt

ery-

pow

ered

ope

ratio

n

peo

ple:

3-6

Fac

ulty

Faci

litie

s:

Inte

rdis

cipl

in-

ary

team

s

with

acc

ess

to

mic

ro-e

lect

roni

cs

fabr

icat

ion

and

clin

ical

tes

t

faci

litie

s

HIgHly mobIle

UltRasonIc ImageRmetabolIc magnetIc Resonance

34

med

ical

imaG

iNG

(con

tinue

d)

Rese

arch

Oppo

rtun

ityEs

timat

ed R

esou

rce

Requ

irem

ents

Appl

icat

ions

of I

nter

est

Rese

arch

Nee

dAd

vant

ages

Met

rics

of P

rogr

ess

dri

ver(

s):

To im

prov

e ut

ility

of m

agne

tic r

eson

ance

tech

nolo

gy for

cen

tral

ner

vous

sys

tem

and

sof

t

tissu

e im

agin

g

mar

ket

size

:

Thou

sand

s of

hos

pita

ls; m

illio

ns o

f pe

ople

wor

ldw

ide

mar

ket

need

s:

Easy

por

tabi

lity

and

asse

mbl

y un

its a

t si

tes

of n

eed

will

impr

ove

avai

labi

lity

and

safe

ty o

f

mag

netic

res

onan

ce im

agin

g

Mag

net

stab

ility

Suf

ficie

nt fi

eld

stre

ngth

and

hom

ogen

eity

Gra

dien

t an

d R

F co

il-

pow

er s

uppl

y/co

ntro

l

elec

tron

ics

Tem

pera

ture

sta

bilit

y/

cool

ing

mec

hani

sms

Dat

a re

cons

truc

tion

and

stor

age.

Red

uce

cost

s/sa

fety

risks

of M

RI m

aint

enan

ce,

incr

ease

ava

ilabi

lity

to

heal

thca

re s

ites

and

to w

ider

pop

ulat

ion

of

patie

nts

Full-

body

3T

MR

I sca

nner

s

curr

ently

req

uire

~50-1

00L

of li

quid

hel

ium

for

coo

ling

per

mon

th. In

stal

latio

n

room

to

be w

ell-s

hiel

ded

&

sepa

rate

fro

m t

he c

ontr

ol

elec

tron

ics.

Sm

alle

r in

siz

e,

requ

ire le

ss e

lect

ric p

ower

,

shie

ldin

g, c

oolin

g.

3-y

ear

goa

l(s)

:

Theo

retic

al d

esig

n

asse

ssm

ent

of a

str

ong

(~1.5

-3T)

, yet

low

-mai

nte-

nanc

e po

rtab

le m

agne

t

5-y

ear

goa

l(s)

:

Con

stru

ctio

n of

the

mag

net,

scan

ner

asse

mbl

y

10-y

ear

goa

l(s)

:

Perf

orm

ance

opt

imiz

atio

n

and

com

petit

iven

ess

with

sta

tiona

ry c

linic

al

MR

I uni

ts

ann

ual c

ost:

~$1-2

M/y

ear

peo

ple:

4-6

Fac

ulty

Prim

arily

phy

sics

and

engi

neer

ing

team

s w

ith

acce

ss t

o M

RI e

quip

men

t

com

pone

nts

and

clin

ical

test

site

s

dri

ver(

s):

Exis

ting

test

s of

bet

a ce

ll fu

nctio

n in

dia

bete

s

fail

to d

istin

guis

h be

twee

n al

tere

d m

ass

and

alte

red

func

tion.

mar

ket

size

:

Dia

bete

s/pr

e-di

abet

es a

ffec

ts >

26

M

Amer

ican

s.

mar

ket

need

:

Emer

ging

the

rapi

es a

re foc

used

on

beta

cel

l

pres

erva

tion,

exp

ansi

on, r

egen

erat

ion

or r

e-

plac

emen

t, bu

t ar

e ha

rd t

o ex

plor

e w

ithou

t

a m

easu

re o

f ce

ll m

ass.

Bet

a ce

lls a

re o

nly

~1%

of pa

ncre

as

Long

cel

l hal

f-life

, litt

le

turn

over

or

grow

th

Mot

ion

and

loca

tion

deep

in g

ut m

ake

imag

ing

diffi

cult

Few

uni

que

mar

kers

for

mol

ecul

ar im

agin

g

Rel

ativ

ely

little

is k

now

n

abou

t th

e bi

olog

y of

the

beta

cel

l and

isle

t.

Impa

ct:

Expl

ore

natu

ral h

isto

ry

of d

iabe

tes;

pot

entia

l for

early

det

ectio

n of

dis

ease

;

impr

oved

end

poin

ts fo

r

clin

ical

tria

ls

ben

efits

/ad

vant

ages

over

cur

rent

cap

abili

ties

:

Cur

rent

ly, m

easu

re

only

glu

cose

or

insu

lin

c-pe

ptid

e, w

hich

is a

poo

r

mea

sure

of fu

nctio

n an

d

cann

ot r

epor

t on

cel

l mas

s

5-t

o-10-y

ear

goa

l(s)

:

a) Id

entif

y ce

ll m

arke

rs

and

spec

ific

ligan

ds

b) E

xplo

re b

iolo

gy o

f

mar

ket/

ligan

d to

pro

ve

imag

ing

appr

oach

is

quan

titat

ive

and

spec

ific

c) T

est

in a

nim

als

and

peop

le

10-y

ear

goa

l(s)

:

Stu

dy im

agin

g ap

proa

ch

in la

rge

clin

ical

pop

ula-

tions

to

prov

e ro

bust

ness

Tota

l spe

nt t

o da

te b

y U

S

and

Euro

pean

fun

ding

agen

cies

is a

bout

$75M

over

10 y

ears

.

Nee

ded

are

dedi

cate

d

inte

rdis

cipl

inar

y fa

cilit

ies

with

imag

ing

and

diab

etes

rese

arch

ers.

ImagIng tHe pancReatIc

beta cell massHIgH-ResolUtIon poRtable mRI scanneR

35

med

ical

imaG

iNG

(con

tinue

d)

Rese

arch

Oppo

rtun

ityEs

timat

ed R

esou

rce

Requ

irem

ents

Appl

icat

ions

of I

nter

est

Rese

arch

Nee

dAd

vant

ages

Met

rics

of P

rogr

ess

dri

ver(

s):

Rea

l-tim

e, la

bel-f

ree

dete

ctio

n, id

entifi

catio

n,

& q

uant

ifica

tion

of b

iolo

gica

l mol

ecul

e

mar

ket

size

:

Hea

lthca

re a

ccou

nts

for

14

% ($

2T)

of

the

US

GD

P; t

he fas

test

gro

win

g se

ctor

in

the

econ

omy

mar

ket

need

:

New

met

hodo

logi

es for

fas

ter,

chea

per

& b

ette

r

diag

nost

ics

will

ena

ble

pers

onal

ized

med

icin

e

base

d on

an

indi

vidu

al’s

bio

chem

istr

y as

de-

term

ined

fro

m m

easu

rem

ents

of th

e pa

tient

’s

bios

igna

ture

(D

NA,

RN

A, p

rote

ins,

met

abol

ites,

etc.

), id

entif

y bi

oter

roris

m t

hrea

ts, &

dev

elop

ther

apeu

tics

agai

nst

biow

arfa

re a

gent

s

Mos

t co

mm

erci

al

devi

ces

are

limite

d

by 1

9th

& e

arly

20th

cent

ury

tech

nolo

gies

.

The

num

ber

of u

niqu

e

biom

olec

ules

is e

nor-

mou

s. D

iscr

imin

atin

g

betw

een

them

req

uire

s

high

ly-s

elec

tive,

sin

gle-

mol

ecul

e de

tect

ors.

Inte

grat

ing

nano

scal

e

sens

ors,

mic

ro/n

anofl

uid-

ics

into

ele

ctro

nic

chip

s

A qu

antit

ativ

e un

der-

stan

ding

of th

e m

easu

re-

men

ts’ fu

ndam

enta

l

phys

ical

bas

is

Impa

ct, i

f su

cces

sful

:

a) A

ffor

dabl

e pe

rson

aliz

ed

med

icin

e

b) O

n-si

te r

apid

det

ectio

n

and

bio-

war

fare

age

nt

rem

edia

tion

ben

efits

/ad

vant

ages

ove

r

curr

ent

capa

bilit

ies:

a) H

ighl

y se

lect

ive

(nee

dle

in a

hay

stac

k ca

pabi

lity)

b) H

ighl

y sc

abal

e

(det

ect

~ 1

000 u

niqu

e

mol

ecul

es/c

hip)

c) L

ow-c

ost

(e.g

.,

< $

1k

per

geno

me)

,

d) E

lect

rical

det

ectio

n w

ith

sing

le-m

olec

ule

sens

itivi

ty

1-t

o-5-y

ear

goa

l(s)

:

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opor

e ba

sed

met

rol-

ogy:

det

ect/

char

acte

rize

RN

A, D

NA,

pro

tein

s, a

n-

thra

x to

xins

; si

ngle

-mol

e-

cule

mas

s sp

ectr

omet

ry

can

disc

rimin

ate

to b

ette

r

than

1.5

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stro

ms

5-y

ear

goa

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:

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elop

mul

tiple

uni

que

nano

pore

s (s

olid

sta

te

& b

iolo

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r gr

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r

sele

ctiv

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plin

g to

fluid

ic s

truc

ture

s &

ele

c-

tron

ic c

hips

10-y

ear

goa

l(s)

:

A de

vice

for

per

sona

lized

med

icin

e &

HLS

appl

icat

ions

ann

ual c

osts

:

$4M

/yea

r

peo

ple:

12 s

cien

tists

, int

erdi

scip

lin-

ary

team

s w

ith a

cces

s to

nano

-ele

ctro

nics

fab

ricat

ion

Faci

lity:

NIS

T N

eutr

on C

ente

r,

& c

linic

al t

est

faci

litie

s

dri

ver(

s):

T-ra

y im

agin

g fo

r ca

ncer

dia

gnos

tics;

biom

etric

s; s

ecur

ity; de

tect

ion

of e

xplo

sive

s

& n

arco

tics,

etc

.

mar

ket

size

:

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ssib

le, l

ower

-cos

t m

edic

al im

agin

g

com

para

ble

to e

.g. X-

ray;

Gro

win

g de

man

d

for

secu

rity

mar

ket

need

s:

a) E

arly

det

ectio

n of

ski

n ca

ncer

b) R

eal-t

ime

on-th

e-fly

det

ectio

n of

exp

losi

ves

and

narc

otic

s

Com

pact

and

effi

cien

t

THz

com

pone

nts

THz

mat

eria

ls, e

.g. fo

r

optic

s

THz

dete

ctor

arr

ays

Dat

a re

cons

truc

tion

and

stor

age

Impa

ct, i

f su

cces

sful

:

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erfu

l im

agin

g &

scr

een-

ing

tech

nolo

gy, a

vaila

bilit

y

to h

ealth

car

e si

tes

and

to

wid

er p

opul

atio

n of

pat

ient

s

adv

anta

ges:

Non

-inva

sive

,

real

-tim

e, h

igh-

reso

lutio

n,

rem

ote

“mat

eria

ls fi

nger

-

prin

ting”

, syn

ergi

stic

with

curr

ent

sem

icon

duct

or

tren

ds

3-y

ear

goa

l(s)

:

Com

pact

and

effi

cien

t

THz

sour

ces

and

optic

s

5-y

ear

goa

l(s)

:

Dem

onst

rate

d in

tegr

ated

syst

em

10-y

ear

goa

l(s)

:

Com

petit

ive

tool

s fo

r

med

ical

imag

ing

and

secu

rity

scre

enin

g

ann

ual c

osts

:

$4M

/yea

r

peo

ple:

12 s

cien

tists

, int

erdi

scip

lin-

ary

team

s w

ith a

cces

s to

nano

-ele

ctro

nics

fab

ricat

ion

Faci

lity:

NIS

T N

eutr

on C

ente

r,

& c

linic

al t

est

faci

litie

s

teRaHeRtz ImagIng systemssIngle molecUle bIoelectRonIcs FoR

HealtHcaRe & secURIty applIcatIons

36

The primary goal of the Bioelectronics Research Initiative (BERI) is to enable and advance

high-impact opportunities at the intersection of two industry sectors — biomedical technol-

ogy and electronics. Initially, BERI will focus on personalized medical diagnostics [PMD]

and monitoring, implantable devices and prosthetics [IDP], and medical imaging [MI]. The

approach will be modeled on existing successful SRC research programs and will comprise

a member-directed, inter-industry consortium to fund relevant university research in bioelec-

tronics. BERI will transfer or make rights available to such technology to its members.

beRI attributes and objectives:

• Support foundational collaborative university research that bridges fundamental pre-com-

petitive research and targeted application opportunities

• Identify a common set of critical challenges and metrics that focus on and accelerate

pre-competitive research

• Coordinate with and synergistically leverage other strategic initiatives, such as relevant

federal agency programs

participating/contributing organization benefits:

• Early and easy access to supported research results

• Access to BERI-funded faculty experts and relevantly educated students

• Royalty-free access to the results from the selected projects

• Easy archival access to supported research results

• Voting rights on the BERI Technical Advisory Boards

participating/contributing organizations Responsibilities:

• People: Assign Governing Council and Technical Advisory Board representatives

• Management: Exercise and leverage SRC’s research management processes

• Stewardship: Provide strategic input on research scope, priorities and direction

• Funding: Assist in securing necessary support to ensure sustained effort

beRI organizational structure

• A Governing Council will provide administrative oversight of the BERI program, and each

participating member will designate one primary and one alternate representative

• Technical Advisory Boards will provide technical guidance and facilitate technology trans-

appendix F: proposed Framework for a bioelectronics Research Initiative

37

fer, and each Governing Council member shall designate one primary and one alternate

for each Board, i.e., PMD, IDP and MI, as warranted.

• As agreed-upon by members, funds may be directed to individual investigators or to large,

multi-university centers. SRC will ensure coordination among university researchers.

SRC serves as the liaison between consortium members and university researchers, and is

responsible for managing the overall program in terms of budget, research agenda/timelines,

IP management, technology transfer and internal/external communications.

governing council Roles and Responsibilities

• Provide administrative oversight of overall program and serve as primary point-of-contact

for their respective companies

• Set high-level strategic direction and corresponding budget allocation

• Approve and help recruit new members

• Review and approve new research initiatives and funding opportunities

• Appoint Technical Advisory Board representatives from their respective companies and

direct technical interactions

• Provide periodic feedback on overall program quality and opportunities for improvement

• Serve as executive advocates for BERI program within their respective companies

technical advisory board Roles and Responsibilities

• Provide technical oversight of the PMD, IDP or MI program and serve as the primary

point-of-contact for technology transfer at their respective companies

• With SRC, develop a compelling strategic plan

• Review new research initiatives and projects

• With SRC, select projects for funding

• Provide periodic feedback on overall program quality and opportunities for improvement

• Serve as advocates for the BERI program within their respective companies, as well

as externally

38

beRI business processes

• SRC solicits white papers based on member-identified research needs and priorities.

• Technical Advisory Board members review the submitted papers and select projects

for funding.

• SRC executes contracts with universities; projects will include deliverables and mile-

stones to measure progress.

• Research results are presented at annual reviews and periodic e-seminars.

• Deliverables, including reports, seminar presentations and pre-publications will be made

available on the SRC website to BERI members.

• Facilitate access to students via networking events at reviews and other forums, and via

electronically accessible resumes.

• Governing Council and Technical Advisory Boards will meet periodically to review the over-

all progress and discuss opportunities for improvement.

Pioneers in Collaborative Research®

P.O. Box 12053 1101 Slater Road

RTP, NC 27709-2053 Brighton Hall, Suite 120

919 941 9400 Durham, NC 27703

On the Web at www.src.org.