WTEC Panel Report on
INTERNATIONAL RESEARCH AND DEVELOPMENT IN BIOSENSING
Jerome Schultz (chair) Milan Mrksich (vice-chair) Sangeeta N. Bhatia David J. Brady Antonio J. Ricco David R. Walt Charles L. Wilkins
World Technology Evaluation Center (WTEC), Inc.
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WTEC PANEL ON INTERNATIONAL RESEARCH AND DEVELOPMENT IN BIOSENSING
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WTEC Panel on
INTERNATIONAL R&D IN BIOSENSING
Final Report
August 2004
Jerome Schultz (chair) Milan Mrksich (vice-chair) Sangeeta N. Bhatia David J. Brady Antonio J. Ricco David R. Walt Charles L. Wilkins
This document was sponsored by the National Science Foundation (NSF) and other agencies of the U.S. Government under awards from the NSF (ENG-0104476) and the Army Research Office (DAAD19-03-1-0067) awarded to the World Technology Evaluation Center, Inc. The government has certain rights in this material. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the United States Government, the authors’ parent institutions, or WTEC, Inc.
ABSTRACT
This report reviews international research and development activities in the field of biosensing. Biosensing includes systems that incorporate a variety of means, including electrical, electronic, and photonic devices; biological materials (e.g., tissue, enzymes, nucleic acids, etc.); and chemical analysis to produce detectable signals for the monitoring or identification of biological phenomena. This is distinct from “biosensors” that employ only biological materials or mechanisms for sensing. In a broader sense, the study of biosensing includes any approach to detection of biological elements and the associated software or computer identification technologies (e.g., imaging) that identify biological characteristics. Topics covered include the national initiatives, interactions between industry and universities, technology and manufacturing infrastructure, and emerging applications research. The panel’s findings include the following: Europe leads in development and deployment of inexpensive distributed sensing systems. Europe also leads in integration of components and materials in microfabricated systems. Europe and Japan both have much R&D on DNA array technology, but the impact is likely to be only incremental. The United States leads in surface engineering applied to biosensing and in integration of analog-digital systems. Both Europe’s and Japan’s communication infrastructures are better suited for networked biosensing applications than those of the United States. Integrated biosensing research groups are more common in Europe and Japan. Additional findings are outlined in the panel’s executive summary.
World Technology Evalution Center, Inc. (WTEC)
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Copyright 2004 by WTEC, Inc. The U.S. Government retains a nonexclusive and nontransferable license to exercise all exclusive rights provided by copyright. WTEC final reports are distributed by the National Technical Information Service (NTIS) of the U.S. Department of Commerce. A list of available WTEC reports and information on ordering them from NTIS is on the inside back cover of this report.
FOREWORD
We have come to know that our ability to survive and grow as a nation to a very large degree depends upon our scientific progress. Moreover, it is not enough simply to keep abreast of the rest of the world in scientific matters. We must maintain our leadership.1
President Harry Truman spoke those words in 1950, in the aftermath of World War II and in the midst of the Cold War. Indeed, the scientific and engineering leadership of the United States and its allies in the twentieth century played key roles in the successful outcomes of both World War II and the Cold War, sparing the world the twin horrors of fascism and totalitarian communism, and fueling the economic prosperity that followed. Today, as the United States and its allies once again find themselves at war, President Truman’s words ring as true as they did a half-century ago. The goal set out in the Truman Administration of maintaining leadership in science has remained the policy of the U.S. Government to this day: Dr. John Marburger, the Director of the Office of Science and Technology (OSTP) in the Executive Office of the President made remarks to that effect during his confirmation hearings in October 2001.2
The United States needs metrics for measuring its success in meeting this goal of maintaining leadership in science and technology. That is one of the reasons that the National Science Foundation (NSF) and many other agencies of the U.S. Government have supported the World Technology Evaluation Center (WTEC) and its predecessor programs for the past 20 years. While other programs have attempted to measure the international competitiveness of U.S. research by comparing funding amounts, publication statistics, or patent activity, WTEC has been the most significant public domain effort in the U.S. Government to use peer review to evaluate the status of U.S. efforts in comparison to those abroad. Since 1983, WTEC has conducted over 50 such assessments in a wide variety of fields, from advanced computing, to nanoscience and technology, to biotechnology.
The results have been extremely useful to NSF and other agencies in evaluating ongoing research programs, and in setting objectives for the future. WTEC studies also have been important in establishing new lines of communication and identifying opportunities for cooperation between U.S. researchers and their colleagues abroad, thus helping to accelerate the progress of science and technology generally within the international community. WTEC is an excellent example of cooperation and coordination among the many agencies of the
U.S. Government that are involved in funding research and development: almost every WTEC study has been supported by a coalition of agencies with interests related to the particular subject at hand.
As President Truman said over 50 years ago, our very survival depends upon continued leadership in science and technology. WTEC plays a key role in determining whether the United States is meeting that challenge, and in promoting that leadership.
Michael Reischman Deputy Assistant Director for Engineering National Science Foundation
1 Remarks by the President on May 10, 1950, on the occasion of the signing of the law that created the National Science Foundation. Public Papers of the Presidents 120: p. 338.
2 http://www.ostp.gov/html/01_1012.html.
ii
TABLE OF CONTENTS
Foreword...... i Table of Contents...... iii List of Figures...... vi List of Tables ...... vii Preface ...... ix
Executive Summary ...... xi
1. Infrastructure Overview
Jerome Schultz
Introduction to the Study...... 1 History of Biosensing Development...... 3 Technology Drivers...... 5 Enablers of Biosensing Technologies...... 6 Biosensing Infrastructure/Investment Trends in the United States...... 7 Biosensing Infrastructure/Investment Trends in Europe...... 11 Biosensing Infrastructure/Investment Trends in Japan...... 15 Summary ...... 17 References ...... 18
2. Optical Biosensing
David R. Walt
Introduction ...... 21 Surface-Based Optical Biosensing...... 22 Biosensing Arrays...... 23 Inexpensive and Distributed Sensors...... 23 Nanostructured Materials...... 24 Application of Molecular Biology to Optical Biosensing...... 26 General Observations...... 27 References ...... 28
3. Electro-Based Sensors and Surface Engineering
Milan Mrksich
Introduction ...... 29 Overview of R&D Activities ...... 30 Underlying Technical Themes...... 31 Relative Strengths of Regional Programs ...... 32 Key Factors for Future Development ...... 33 Observations and Conclusions...... 33 References ...... 34
4. Cell and Tissue-Based Sensors
Sangeeta N. Bhatia
Introduction ...... 35 Scope of Cell-Based Sensors ...... 35 Key Science/Technology Issues ...... 37 Summary ...... 40 Conclusions ...... 41 Recommended Reading...... 41
5. Mass Spectrometry and Biosensing Research
Charles L. Wilkins
Introduction ...... 43 Mass Spectrometry Background...... 43 Mass Spectrometry Research in Europe ...... 46 Mass Spectrometry Research in Japan...... 48 Conclusions ...... 48 References ...... 49
6. Microfabricated Biosensing Devices: MEMS,Microfluidics, andMassSensors
Antonio J. Ricco
Introduction ...... 51 Definitions and Scope...... 52 R&D: Drivers, Trends, and Challenges ...... 52 Microfluidic Systems...... 58 Mass Sensing: Mature Quartz and Evolving Silicon Technologies...... 60 Summary Findings: General Trends and Specific Opportunities...... 63 Conclusion: Important Targets for BioMEMS ...... 66 References ...... 66
7. Information Systems for Biosensing
David J. Brady
Information System Challenges in Biosensing ...... 69 Biosensing Information Systems in the United States ...... 70 Biosensing Information Systems in Europe...... 72 Biosensing Information Systems in Japan ...... 74 Opportunities ...... 74 References ...... 74
APPENDICES
A. Panel Biographies ...... 79
B. Site Reports — Europe and Australia
Biacore Sweden...... 83 Cranfield University at Silsoe...... 84 DiagnoSwiss ...... 88 Dublin City University ...... 89 Eberhard Karls University Tübingen ...... 91École Normale Supérieure (ENS)...... 96École Polytechnique Fédérale de Lausanne (EPFL), Institute of Biomolecular Sciences...... 98École Polytechnique Fédérale de Lausanne (EPFL), Institute of Molecular and Biological
Chemistry ...... 99 Griffith University, Gold Coast Campus ...... 103 Institute for Chemical and Biochemical Sensors (ICB)...... 105 Linköping University...... 108 Oxford Glycosciences (UK), Ltd...... 114 Potsdam University...... 115 Ruprecht-Karls University Heidelberg...... 119 Swiss Federal Institute of Technology (ETH), Zürich, Department of Chemistry...... 125 Swiss Federal Institute of Technology (ETH), Zürich, Physical Electronics Laboratory...... 128 University of Cambridge ...... 130 University of Manchester Institute of Science and Technology (UMIST) ...... 132
University of Neuchâtel...... 134 University of Regensburg ...... 139 University of Twente MESA+ Institute...... 141 University of Twente Laboratory of Biosensors...... 144 The University of Warwick ...... 145
C. Appendix C. Site Reports — Japan
Initium, Inc...... 147
Japan Advanced Institute of Science and Technology (JAIST)...... 150
Kyushu University...... 152
Matsushita Electric Industrial Co., Inc. (National/Panasonic)...... 154
The National Institute of Advanced Industrial Science and Technology (AIST) Kansai
(Osaka ) Center...... 158
National Institute of Advanced Industrial Science and Technology (AIST) Tsukuba
Central, Research Center of Advanced Bionics...... 160
National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba Central,
Division of Biological Resources and Functions Biosensing Technology Research Group...... 162
National Rehabilitation Center for Persons with Disabilities ...... 164
RIKEN (Wako Main Campus), Discovery Research Institute, Bioengineering Laboratory...... 167
RIKEN (Wako Main Campus), Frontier Research Program, Local Spatio-Temporal
Functions Laboratory...... 170
Tokyo Institute of Technology, Graduate School of Bioscience and Biotechnology...... 173
Tokyo University of Agriculture and Technology, Department of Biotechnology ...... 176
University of Tokyo, Department of Chemistry ...... 188
University of Tokyo, School of Pharmaceutical Sciences...... 191
D. NIH Grants Related to Biosensing, CY 2002...... 193
E. NSF-Sponsored Projects Related to Biosensing, CY2002...... 202
F. DOD/DARPA Programs Related to Biosensing ...... 211
G. U.S. Army Research Office-Funded Projects Related to Biosensing, as of March 2004 ...... 213
H. U.S. Department of Energy Research Related to Biosensing (1999)...... 215
I. European Union 6th Framework Programme (2002–2006)...... 217
J. Europe and Japan Patents Related to Biosensing, 1999–2003 ...... 222
K. Bibliometric Study of World Biosensors Research, 1997–2002 ...... 242
L. Glossary ...... 258
LIST OF FIGURES
1.1 First “enzyme” electrode — an electrode system for continuous monitoring in cardiovascular surgery...... 4
1.2 A simplified matrix that can lead to a variety of combinations of molecular recognition elements and transducers to produce biosensors...... 5
1.3 Evolutions of the confluence of technologies as related to biosensing in the field of clinical analytical chemistry...... 6
1.4 Subcutaneousglucose sensor1 mm wide under development by Medtronic/MiniMed Corp...... 7
1.5 Fluorescence pattern on an array chip for identifying DNA fragments ...... 7
1.6 Growth ofthe biotechnology industry in Berlin-Brandenburg region...... 14
1.7 Product areas for the biotechnology industry in Berlin-Brandenburg region...... 14
1.8 Cooperative Research Center at TUAT...... 15
1.9 Tokyo University of Technology’s Katayanagi Advanced Research Laboratories building ...... 16
2.1 Examples of holographic biosensing before and aftera test...... 23
2.2 Inexpensive optical sensor for testing integrity of meat packaging ...... 24
2.3 Nanoparticle array localized surface plasmon resonance spectroscopy (LSPR) spectroscopy and nanostructured gold materials on a substrate provide local enhancement in the plasmon resonance ...... 25
2.4 Porous Si particles can be fabricated and used to sense analytes ...... 25
2.5 A fluorescent indictor for protein phosphorylation in living cells ...... 26
3.1 Oligo(ethylene glycol)-terminated self-assembled monolayers...... 31
4.1 Cell-based sensing; cells sense extracellular species via membrane-bound or nuclear receptors...... 35
4.2 Control of cell physiology using micropatterning...... 38
4.3 Integration of microtechnology and biological species...... 40
4.4 Automation and parallel screening...... 40
5.1 A miniaturized cylindrical ion trap with a commercial ion trap for comparison ...... 44