ralph k. cavin, iii, daniel j.c. herr, celia i. merzbacher, · targeted bioelectronics research can...
TRANSCRIPT
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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ectio
n
Alte
rnat
ive
Sol
utio
ns
Enab
le m
ulti-
dim
ensi
onal
cell
stud
y pl
atfo
rms
Res
earc
h tim
e/co
st
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
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)
:
Nan
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
Ang
stro
ms
5-y
ear
goa
l(s)
:
Dev
elop
mul
tiple
uni
que
nano
pore
s (s
olid
sta
te
& b
iolo
gica
l) fo
r gr
eate
r
sele
ctiv
ity.
Cou
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
:
Acce
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
:
Pow
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.