Grand Challenge Workshop Series
Nanotechnology Innovation
for
Chemical, Biological, Radiological, and Explosive (CBRE):
Detection and Protection
Final Workshop Report
November 2002
in cooperation with
The AVS Science and Technology Society
About this Document
A workshop on May 2-3, 2002, was organized by the AVS and coordinated with a meeting of the
AVS Science and Technology Society held in Monterey, California on May 1 and 2, 2002. The
workshop was supported in part by the NNCO. Selected participants in the AVS meeting were
invited to stay an extra day at the workshop. This report summarizes the workshop determination of
the opportunities and challenges for nanoscience and technology research as applied to the NNI
Grand Challenge on Chemical, Biological, Radiological, and Explosive (CBRE) Detection and
Protection.
About the Cover
BioCOM chip developed at the University of California, Berkeley, based on the observation of
chemo-mechanical microcantilever beam actuation induced by biomolecular binding. The chip is
currently being developed for high-throughput multiplexed biomolecular analysis. This chip-level
microcantilever array is expected to provide a quantitative, label free, and low cost platform for
detection of various biomolecules, such as DNA and proteins. This illustrates the potential for
nanotechnology-based approaches to detection of and protection from chemical, biological,
radiological, and explosives threats (courtesy of A. Majumdar, U.C. Berkeley).
Workshop Report
Nanotechnology Innovation
for
Chemical, Biological, Radiological, and Explosive (CBRE):
Detection and Protection
Recommended Investment Strategy
Workshop Participants
May 2-3, 2002, Monterey, CA:
Dr. James Baker
Dr. Richard Colton
Dr. Heidi Schroeder Gibson
Dr. Michael Grünze
Dr. Stephen Lee
Dr. Kenneth Klabunde
Dr. Charles Martin
Dr. James Murday
Dr. Thomas Thundat
Dr. Bruce Tatarchuk
Dr. Keith Ward
University of Michigan
Naval Research Laboratory
U.S. Army Natick Soldier Center
University of Heidelberg, Germany
Army Research Office
Kansas State University
University of Florida
Naval Research Laboratory
Oak Ridge National Laboratory
Auburn University
Office of Naval Research
Any opinions, conclusions, or recommendations expressed in this material are those of the workshop participants and do not necessarily reflect the
views of the participants’ home institutions or of the United States Government.
Nanotechnology Innovation
for
Chemical, Biological, Radiological, and Explosive (CBRE): Detection and Protection
Table of Contents
Executive Summary............................................................................................................................3
I. Vision ................................................................................................................................................4
II. Relevance of Nanotechnology to CBRE Detection and Protection .....................................................4
Detection
Protection
III. Nanoscience/Nanotechnology Research Opportunities ....................................................................10
Short-term (1-5 yr), Mid-term (5-10 yr), and Long-term (10-20 yr) Transitions
Nanoscience Opportunities for Detection: Miniaturized, Intelligent Sensors (MIS)
Nanoscience Opportunities for Protection/Remediation/Prevention (PR&P)
IV. Infrastructure ..................................................................................................................................14
V. Recommended Investment Strategy .................................................................................................15
VI. Conclusion ......................................................................................................................................18
Appendix A: Evolving Nanotechnology Success Stories Pertinent to CBRE ........................................19
1.
Nanoparticles for Chemical and Biological Agent Decontamination
2.
Nanoparticles for Sensitive, Selective Detection of CBRE agents
3.
Microcantilevers: An Ideal Sensor Platform for Terrorist Threat Detection
4.
Application of Nanomaterials to High Rate Mitigation of Chemical/Biological Threats
5. Nanostructured Films for Chemical Sensing
6. Rapid Development of Proteins for the Detection of Weapons of Mass Destruction
7. Non-Invasive Monitoring of Cells for the Diagnosis of Pathogen Exposure and Infection
Appendix B: Acronyms .........................................................................................................................27
Appendix C: List of Participants and Contributors ................................................................................28
1
Nanotechnology Innovation for CBRE: Detection and Protection
Examples of nanotechnology applied to detection of and protection from chemical,
biological, radiological, and explosive agents, from Appendix A of this report.
2
Nanotechnology Innovation for CBRE: Detection and Protection
Executive Summary
Solutions to the problems of homeland security will be very complex and expensive to implement. Why
should nanoscience/nanotechnology deserve an allocation from the limited resources that will be available?
Nanostructures, with their small size, light weight, and high surface-to-volume ratio, will improve by orders
of magnitude our capability to:
a) detect chemical, biological, radiological, and explosive (CBRE) agents with sensitivity (potentially as
little as a single agent entity) and selectivity (microfabricated sensor suites and molecular recognition)
b) protect through filtration, adsorption, destructive adsorption or neutralization of agents (nanoporosity,
high surface-to-volume nanomaterials, and reactive surface sites)
c) provide site-specific in-vivo prophylaxis.
The use of nanoscale sensors for CBRE can critically impact national security programs, by providing
sensitive, selective, and inexpensive sensors that can be deployed for advance security to transportation
systems (protection for air, bus, train/subway, etc.); military (protection for facilities, equipment and
personnel); Federal buildings (White House, U.S. embassies, and all other Federal buildings); customs (for
border crossings, international travel, etc.); civilian businesses; and schools. Nanotechnology-based
materials will be essential to protective garb for emergency response teams and hospital staff coping with
chemical or biological (CB) incidents. New nanotechnology approaches to acceptable decontamination of
apparatus and building spaces are also needed, as highlighted by the prolonged efforts to decontaminate
anthrax in the Senate Hart Office Building. The FY 03 NNI budget proposal identifies CBRE detection and
protection as one of 9 NNI “grand challenges” – targets for long-term benefits to the nation that could be
expected from the NNI’s basic research programs. The goal of this workshop was to recommend a plan of
action for research and development under the auspices of the NNI aimed at realizing the promise of the
CBRE grand challenge.
The workshop participants were polled to establish recommendations for needed science and technology
(S&T) funding on the basis of three criteria:
1) the importance of technology in coping with problems posed by CBRE protection/detection
2) the potential for nanotechnology to contribute significant improvements to that technology
3) the availability of resources/expertise ready to utilize effectively any funding allocation.
An S&T goal of $100 million/year by FY05 was identified with a distribution of 50% in sensing, 30% in
protection and 20% in remediation.
Fundamental research will continue to be crucial to the full exploitation of nanotechnology. However, the
realization of the short- and mid-term goals identified at the workshop will require availability of growing
amounts of both applied research and Small Business Innovative Research (SBIR) funds. Approximately
one half of the FY05 $100 million should be devoted to the explicit task of developing the technology
options. To accelerate the transition of nanoscience discovery into technology, the government agencies
addressing new technologies for homeland defense — the DOD Joint Service Chemical and Biological
Defense Program, the Defense Threat Reduction Agency, the Interagency Technical Support Working
Group, the DOE Radiological and Environmental Protection Program, and the DOT Weapons and
Explosives Detection Program — should be knowledgeable of and actively participate in the nanotechnology
programs.
The goal of $100 million by FY05 would consume about 10-15% of the anticipated U.S. NNI funding. That
is a significant fraction of the NNI investment and, if met, might be detrimental to the rate of progress toward
other NNI grand challenge goals. The CBRE terrorist threat is not unique to the United States. It is strongly
recommended that joint programs be developed to incorporate the excellent and extensive European and
Pacific theater nanoscience into this CBRE detection/protection grand challenge program.
3
Nanotechnology Innovation for CBRE: Detection and Protection
Nanotechnology Innovation
for
Chemical, Biological, Radiological, and Explosive (CBRE): Detection and
Protection
I. Vision
Nanostructures, with their small size, lightweight, and high surface-to-volume ratio, will improve by orders
of magnitude our capability: a) to detect CBRE agents with sensitivity (potentially a single agent entity) and
selectivity (microfabricated sensor suites, molecular recognition); b) to protect through filtration, adsorption,
destructive adsorption or neutralization of agent (nanoporosity and high surface-to-volume nanomaterials);
and c) to provide site-specific prophylaxis.
II. Relevance of Nanotechnology to CBRE
1
Explosives were introduced into warfare about 1100 AD and now dominate military weaponry. The use of
explosives by terrorists is also common, with the 1993 bombing of the World Trade Center in New York
City, the 1995 bombing of the Alfred P. Murrah Federal Building in Oklahoma City, the 2000 bombing of
the USS Cole in Yemen, and numerous 2002 suicide bombings in Israel as dramatic recent examples. In
addition to political and symbolic targets, there is considerable threat to drinking water, wastewater treatment
plants, public transportation systems, and other important parts of our infrastructure such as chemical
manufacturing plants and food processing industries.
While not as prevalent as explosives, the use of chemical/biological agents as a warfare or terrorist weapon
reoccurs throughout history2. Scythian archers dipped arrowheads in manure and rotting corpses to increase
lethality millennia ago. Tartars hurled dead bodies with plague over the walls of fortified cities in the
fourteenth century. Smallpox-infested blankets were given to unfriendly native Indian tribes by the British
during the French and Indian war. WWI saw extensive use of chemical warfare. The Japanese introduced
plague into Chinese cities in WWII. The Rajneeshee’s cult attacked cities in Washington State with
salmonella in 1984. The Aum Shinri Kyo deployed both anthrax and sarin gas in Tokyo in the early 1990s.
Nature, more so than man, has proven to be a spectacular “terrorist” – smallpox, black plague, influenza, and
HIV – have taken millions of lives. Diamond3 estimates that 95% of New World Indians may have died from
European introduced (mostly unintentional) diseases.
Thus far no terrorist release of radioactive materials has occurred; however, accidental exposures in the
nuclear power industry validate the potential problem, Chernobyl, Ukraine in 1986 being the most dramatic
example. Nuclear power plants, with their concentration of radioactive fuel and waste materials, are
considered a potential target for terrorist action4. This, in addition to the possibility of nuclear devices on the
black market, establishes the threat and need for enhanced radiological screening, sensing, and clean-up.
1
A History of Warfare, J. Keegan (Alfred A. Knopf, New York, 1997).
Germs, J. Miller, S. Engelberg, and W. Broad (Simon and Schuster, New York, 2001).
3
Guns, Germs and Steel: the Fates of Human Societies, J. Diamond (W.W. Norton and Company, New York, 1999) pg
211.
4
“Chemical, Biological, Radiological and Nuclear (CBRN) Terrorism,” Report #2000/02, Canadian Security
Intelligence Service.
2
4
Nanotechnology Innovation for CBRE: Detection and Protection
One may expect nanotechnology to make significant contributions to the detection, protection, remediation
and prophylaxis of CBRE events. Indeed, the DOE Basic Energy Sciences workshop report on “Basic
5
Research Needs to Counter Terrorism” cites nanoscience as one of the research directions to be emphasized .
Selected examples of evolving nanotechnology pertinent to CBRE detection and protection are provided in
Appendix A.
IIA.
Detection
Small amounts of chemical, biological, or radiological agents (see Table 1) can potentially inflict much
larger scale damage to people than can equivalent amounts of explosive.
Table 1
Comparative Lethality of Selected Toxins, Chemical
Agents, Biological Agents and Radiological Hazards
Agent
Botulinum Toxin
Diphtheria Toxin
Ricin
VX
GB
Anthrax
Plutonium
Lethal Dosage (LD50 — •g/kg body weight)
0.001
0.10
3.0
15.0
100.0
0.004-0.02*
1
Source
Bacterium
Bacterium
Castor Bean
Chem Agent
Chem Agent
Bacterium
Nuclear Fuel
*Anthrax calculations based on a spore volume of 5.0E-10 •l, an assumed spore density of 1.0 g/ml, and the LD50
(lethal dosage to 50% of the population) estimated from the Sverdlovsk Model of 8,000 to 45,000 spores. Since
theoretically one organism is capable of causing infection under the right conditions, body weight of the subject is not
necessarily relevant. Thus, the value for anthrax is not a true LD50, but could be considered as the weight of spores that
would kill 50% of individuals in a statistically normal distribution.
Micrograms of anthrax and milligrams of nerve agent are sufficient to kill a person, as compared to grams of
high explosive. However, while larger amounts of explosive are necessary for deleterious consequences,
their detection in the air is made difficult by low vapor pressures (particularly true for military explosives).
As a practical consequence, it is necessary to find technology that will detect very small amounts of all
CBRE material. As an illustration, the DOD detection requirements for chemical agents are listed in Table 2.
What role might nanotechnology play in the drive toward better detection against CBRE threats? The
nanoscale offers the potential for orders of magnitude improvements in sensitivity, selectivity, response time,
and affordability.
Sensitivity
For the nanoscience instrumentation being developed to measure and manipulate individual atoms with subnanometer precision, one pathogen or even one chemical molecule is huge. The detection of a single CBRE
entity comes within the realm of possibility.6 However there is still the nontrivial problem of getting that
single entity to the location where it can be detected.
5
“Basic research needs to counter terrorism,” Workshop Report, Office of Basic Energy Sciences, U.S. Department of
Energy. http://www.sc.doe.gov/production/bes/counterterrorism.html (Feb. 2002).
6
G.U. Lee, D.A. Kidwell, and R.J. Colton, “Sensing molecular recognition events with atomic force microscopy,”
Langmuir 10, 354-7 (1994).
5
Nanotechnology Innovation for CBRE: Detection and Protection
Table 2
Joint Chemical Agent Detector Requirements
Agent*
VX
Threshold
Concentration
3
JCAD (mg/m )
1
0.1
0.04
0.001*
Threshold
Response Time
Max (sec)
Relative
Humidity
(%RH)
Temperature
0
(C )
<10
<30
<90
<1800
5 to 100
-10 to +49
GA, GB, GD
&
GF
HD, L
&
HN3
1
<10
0.1
<30
5 to 100
-30 to +49
<1800
0.001**
<10
50
-30 to +49 (HD &L)
2
<120
5 to 100
-15 to +29 (HN3)
0.02
<1800
2500
<10
AC
5 to 100
-32 to +49
22
<60
CK
20
<60
5 to 100
-32 to +49
* See Appendix B for glossary of acronyms and other specialized terminology used in this report.
** Maximum alert response time at low concentration (may use preconcentrator unit)
Diagnostic speed is a real issue for chemical, biological, and radiological exposures. For instance, seconds
may be all the time one has to respond to threat level quantities of nerve agent. Even with the slower
incapacitation rates for biological and radiological agents, detection times of seconds to minutes could limit
the exposure and simplify subsequent prophylactic action. If one can solve the problem of rapidly bringing
sufficient quantity of agent into the detection volume, then nanostructures do minimize the time to diffuse
into and out of that volume. The nanoscale should also enable inexpensive sensor suites so that one can
afford to distribute them prolifically and minimize the distance from a threat to a sensor.
Selectivity
Selectivity is no less important than sensitivity. A detection system with frequent false positives (false
alarms) is quickly ignored (more likely discarded), while false negatives may lead to death. If presented with
a small sample of unknown material for identification, the analytical chemist would turn to multiple, room
sized, sophisticated analytical tools – nuclear magnetic resonance, infra-red/raman spectroscopy, mass
spectrometry, elemental analysis – to ensure the identification. Reducing the size of a diagnostic tool
generally leads to loss of performance. However, the nanoscale does enable the potential for sensor suites,
where multiplicity in the tens to thousands may compensate for the loss of performance in any single
measurement. Further, nanoscience analytical tools make possible the measurement of additional molecular
properties – such as size, shape, and mechanics – not accessible by conventional analytical chemistry tools7.
Sample Collection/Preconcentration
The collection of airborne or surface-attached samples representing a potential chemical, biological,
radiological, or explosive threat is a key part of a point detection system. Nanostructures can be sufficiently
small and light to avoid gravitational settling. There is the possibility for maneuverable nanostructures that
would circulate through large volumes of air or water and then be proactively drawn (through
magnetic/electric field coupling) to the sensor. A front-end collection system must match the flow
7
“Direct measurements of the interaction of single strands of DNA with the atomic force microscope,” G.U. Lee, L.
Chrisey, and R.J. Colton, Science 266, 771-3 (1994); “A biosensor based on force microscope technology,” D.R. Baselt,
G.U. Lee, and R.J. Colton, J. Vac. Sci. Technol. B14, 789-93 (1996).
6
Nanotechnology Innovation for CBRE: Detection and Protection
impedance of the nano-detection sensor for the system to be fully functional. The most efficient collection
systems would employ some type of preconcentration media, which requires research and development of
nanoscale coatings (e.g., development of monolayer polymer coatings for chemically selective, rapid
absorption/desorption of agent molecules).
In-vivo Sensing
Nanotechnology will accelerate the development of sensing systems capable of in-vivo operation. One can
envision sensors that sample body or cellular chemistry to detect the very early stages of exposure to
chemical, biological, or radiological agents.
Radiological Sensing
The nanoscale offers a mixed opportunity for the detection of radiation. As with the detection of
chemical/biological threats, the properties of a nanostructure will be significantly affected by the capture of a
high-energy particle. However, in contrast the chemical/biological threat, nanoscale dimensions will make
that capture difficult; the mean free path is longer than a nanometer for detection of the distinguishing
neutrons and gammas of relevant isotopes. Detection in nanoscale ranges might be possible for thermal
neutrons and airborne radioisotopes using solid-state detection techniques. There has already been a
significant amount of work to reduce the volume of radiation detectors. That miniaturization, coupled with
the miniaturized chemical and biological detection devices, will enable the incorporation of chemical,
biological, and radiological (CBR) detection into a single package.
Remote Detection
Remote sensing can be accomplished either by unattended sensor suites or by stand-off detection. The
former are essentially the point detectors discussed above, but with special emphasis on achieving obscurity
(small, passive) and low power. Communication with the suite would need be rapid (for power and
covertness reasons); the incorporation of nanoelectronics for local intelligence will enable transmission of
compact information, not voluminous raw data.
Stand-off detectors may offer a more flexible approach to sensing, and require active and/or passive
detection of photons. One-dimensional nanotechnology is already providing variable frequency lasers in
spectral ranges that might provide molecular fingerprints8.
These new sources, coupled with onedimensional approaches to sensitive, narrow band detection of photons, may lead to miniaturization of
spectrometers. The use of nanostructures in photonic band gap devices should lead to further innovations.
Potential Applications
The use of nanoscale sensors for CBRE can critically impact national security programs and emergency
response team safety by providing sensitive, selective, and inexpensive sensors that can be deployed for
advance security to transportation systems (security protection for air, bus, train/subway, etc.); military (for
protection of facilities and equipment); Federal buildings (White House, U.S. Embassies, and all other
Federal buildings); customs (for border crossings, international travel, etc.); civilian businesses; and schools.
The potential impact is vast and critical.
IIB.
Protection
Gas mask filters used in nuclear, biological, and chemical (NBC) applications remove toxic chemicals by a
process that is essentially WWI technology. The material responsible for chemical vapor/gas removal is an
activated carbon with metal oxides (such as, copper, zinc, molybdenum, and silver) impregnated in the larger
carbon pores using a Whetlerite method. For additional protection against blood gases, triethylenediamine
(TEDA) is added. The NBC filters rely on high surface areas for efficient adsorption of low vapor pressure
chemical warfare agents or toxic industrial compounds. Higher vapor pressure chemicals, not removed
8
“Quantum cascade lasers,” F. Capasso, C. Gmachl, D.L. Sivco and A.Y. Cho, Physics Today 55(5), 34-40 (2002).
7
Nanotechnology Innovation for CBRE: Detection and Protection
efficiently by adsorption, are retained by chemical reaction with the carbon's impregnates.
requirements for protective masks and clothing are itemized in Tables 3 and 4.
General
Table 3
9
CBW Protection Requirements for Filter Masks
99.990 % (smoke concentration of 100 •g/L, flow rate of 32 L/min;
avg particle diameter 0.3 •m)
Aerosol Filtration
Canister Use Life (Gas Exposure)
Sarin
CK
DMMP
3
3
83 min (to break point of 0.04 mg/m at concentration 4,000 mg/m )
3
3
30 min (to break point of 0.04 mg/m at concentration 4,000 mg/m )
3
3
59 min (to break point of 0.04 mg/m at concentration 3,000 mg/m )
Table 4
Chemical Protective Clothing Performance Requirements10
Garment Type
MOPP Protective
Overgarment
Challenge Type
Vapor
HD,TGD,VX
Liquid
HD,TGD,VX
Challenge Level
5,000 ct
3
(mg-min/m )
2
5-10 g/m
MOPP Protective
Undergarment
Vapor
HD, TGD, VX
Liquid
Vapor
CBs,TICs, POLs, Rocket Fuels
Liquid
CBs,TICs, POLs, Rocket Fuels
Vapor
HD,VX,GB,L
Liquid
HD,VX,GB,L
5,000 ct
3
(mg-min/m )
2
10 g/m
5,000 ct
STEPO (self-contained toxic
environment protective outfit)
ITAP (improved toxicological agent
protective ensemble)
2
10 g/m
5,000 ct
3
(mg-min/m )
2
10 g/m
Adsorbents
Activated carbon is replete with pores with dimensions ranging from about 0.5 nm to 500 nm; it is an
empirically derived nanotechnology. Nanoscience can provide new opportunities for high surface area
adsorbents and molecular templating that augments the bonding strength. Many toxic industrial chemicals
and acid gases (CS2, HCN, SO2, H2SO4, etc.) are not well adsorbed by charcoal or activated carbon.
Nanoparticle oxides offer a possible answer here, because they can be tailored to have solid acid or solid base
properties; the adsorptive properties can be tailored from the “ground up.” Nanostructures also offer the
possibility for selective adsorption of radioactive materials (not due to the radioactivity, but to other known
chemical properties of these materials).
Filtration/Separation
Collective protection systems and protective clothing generally utilize fibrous filters to remove agents. High
efficiency particulate air (HEPA) filters can be effective against particulates; even the biological toxins that
might be dispersed as aerosols could be filtered out by HEPA. The use of nanotubes, nanofilaments, and
nanoporous membranes might make these filters even more effective, and might incorporate catalytic
9
Military Performance Standard MIL PRF 51560A (EA)
Joint operational requirement document (JORD) for a lightweight integrated nuclear, biological, and chemical (NBC)
protective garment (No. NBC 215.1,1995)
10
8
Nanotechnology Innovation for CBRE: Detection and Protection
degraders as well. For example, it has been shown that membranes containing nanotubes with diameters of
molecular dimensions can be used to filter small molecules on the basis of size, and that chemical and
11
biochemical reagents can be incorporated to make highly selective molecular recognition membranes .
12
Nanoporous membranes have been shown capable of removing virus particles from water ; NASA has an
SBIR project to evaluate a ceramic nanofiber filter to remove viruses from drinking water on the
International Space Station13. Smart membranes are also under development that respond to particular
chemical or biological agents and switch on in response to their presence14. Nanosized molecules can be
tailored for the sequestration of radionucleotides15. Catalytic and photocatalytic agents added to HEPA filters
offer the real possibility to make these structures self-cleaning and self-sterilizing thereby greatly extending
system life while reducing life-cycle costs. Reductions in power and operational costs may also be provided
by electrically conductive filter media, which feature reduced pressure drop (larger pore size) yet higher
capture efficiency when used as part of a catalytically or photocatalytically regenerable HEPA collection
electrode in a electrostatic precipitator.
Decontamination and Neutralization of Dispersed Agents
Decontamination and neutralization of harmful moieties can also benefit from nanoscale materials. To
ensure their general effectiveness and to simplify logistics, the military decontamination solutions have
traditionally been highly aggressive chemicals. The Navy decontamination (decon) solution (ASH/SLASH)
utilizes hypochlorous acid; the Army decon solution (DS2) utilizes sodium hydroxide and diethlenetriamine.
Unfortunately, while effective against agents, these chemicals also attack incidental materials, including
human skin.
Catalytic nanostructures, both inorganic and organic, should improve this situation as nanoscience provides
clearer understanding of composition/structure versus function relationships. Nanoparticles such as
nanotubes that incorporate biochemical catalysts will lead to an arsenal of smart nanoparticles for specific
remediation applications. The key point here is that such smart nanoparticles will allow for reduced use of
highly aggressive chemical systems. Nanophase photocatalytic materials incorporated into paints, pigments,
and other coatings offer the opportunity to provide self-cleaning and self-sterilizing surfaces16; they would
operate in a passive or active mode with significantly less risk and side effects than current decontamination
procedures and chemicals. Nanoemulsions have been shown to be very effective against a number of
biological infective agents such as anthrax17. Further, as the role of nanostructures in cellular activity is
better understood, new mechanisms to disrupt and neutralize harmful pathogens are being discovered18.
11
“Antibody-based bio-nanotube membranes for enantiomeric drug separations,” S.B. Lee, D.T. Mitchell, L. Trofin,
T.K. Nevanen , H. Soderlund, and C.R. Martin, Science 296(5576) 2198-2200 (2002).
12
“French drink tap water? Oui, if it’s nanofiltered,”
Genevieve Oger, Smalltimes News article
www.smalltimes.com/document_display.cfm?document_id=394
13
“Filters based on novel bioactive nano fibers,” F. Tepper and L. Kaledin, Argonide Corporation,
www.argonide.com/bioactive.htm
14
“Ion channel mimetic micropore and nanotube membrane sensors,” E.D. Steinle, D.T. Mitchell, M. Wirtz, S.B. Lee,
V.Y. Young, and C.R. Martin, Analytical Chemistry 74(10), 2416-22 (2002).
15
“Selective metals determination with a photoreversible sprobenzopyran,” G.E. Collins, R.E. Shaffer, V. Michelet, and
J.D. Winkler, Analytical Chemistry 71, 5322 (1999); “Microfabricated capillary electrophoresis sensor for uranium
(VI),” G.E. Collins and Q. Lu, Analytica Chimica Acta 436(2), 181-189 (2001).
16
“Application of titanium dioxide photocatalysis to create self-cleaning building materials,” R. Benedix, F. Dehn, J.
Quaas and M. Orgass, Leipzig Annual Civil Engineering Report (5), 157 (2000). Institut for Massivbau und
Baustofftechnologie, Wirtshaftswissenshhaftliche Fakutat, Leipzig, FRG.
17
“A novel surfactant nanoemulsion with a unique non-irritant topical antimicrobial activity against bacteria, enveloped
viruses and fungi,” T. Hamouda, A. Myc, R. Donovan, A.Y. Shih, J.D. Reuter, and J.R. Baker, Microbiological
Research 156(1), 1-7 (2001).
18
“Antibacterial agents based on the cyclic D,L-alpha-peptide architecture,” S. Fernandez-Lopez, H.S. Kim, E.C. Choi,
M. Delgado, J.R. Granja, A. Khasanov, K. Kraehenbuehl, G. Long, D.A. Weinberger, K.M. Wilcoxen, and M.R.
Ghadiri, Nature 412(6845), 452-5 (2001).
9
Nanotechnology Innovation for CBRE: Detection and Protection
Large-Scale CBRE Mitigation and Chemical Processing
The destruction of old, existing U.S. chemical agents illustrates a different aspect of “neutralization.” The
destruction of quantities of agents poses major problems – the extreme toxicity of chemical/biological agents
requires highly effective destruction. The incorporation of nanomaterials into chemically reactive structures
can take advantage of the intrinsic nanostructure surface kinetics and selectivity, while providing appropriate
micro- and mesostructure to accommodate the required transport process, thermal management, low pressure
drop, etc.
Green Manufacturing
Nanotechnologies hold the promise of less toxic chemical processing. Hence, hazardous materials and
wastes may be eliminated or minimized and their potential for use in terrorist attacks reduced. For example
nanocrystalline metal oxides have been shown to enable the following chemistries: (1) catalytic solventless
dehydrochlorination of chloroalkanes, (2) catalytic selective alkylation reactions using superbase
nanomaterials, (3) catalytic alkane isomerization reactions using super acid nanomaterials, and others.
Potential Applications
Perhaps even more important than adequate sensing, protective clothing will be essential to emergency
response teams and hospital staff coping with CB incidents. New nanotechnological approaches to
acceptable decontamination of apparatus and building spaces are needed, as highlighted by the prolonged
efforts to decontaminate the anthrax in the Hart Senate Office Building.
III. Nanoscience/Nanotechnology Research Opportunities
IIIA. Transition Opportunities
The U.S. National Nanotechnology Initiative (NNI) has its prime focus on science. It traditionally takes 1020 years for scientific discovery to evolve into fielded technology. However, the NNI builds on two decades
of Federal funding at the nanoscale. There is a range of opportunities for commercial products, some with
near-term reach (1-5 year), others likely in the mid-term (5-10 years), and yet others where complexity or
lack of present understanding will require long-term science investment (10-20 years).
Investigator
Baker
Doshi
Hellinga
Klabunde
Lieber
Martin
Mirkin
Russell
Smalley
Snow
Tatarchuk
Thundat
Walt
10
Table 5
Potential Near-Term Nanotechnology with CBRE Impact
Institute
Technology
Company
Michigan
nanostructured bio decon NanoBio Corp.
polymer nanofibers
eSpin
Duke U.
Tailored biosensors
Johnson & Johnson
Kansas State
nanocluster agent
Nanoscale Materials
catalysis
Harvard
nanotube sensors
Nanosys
U. Florida
nanotube membranes
Broadley-James Co.
Northwestern
nanoAu biological
Nanosphere
sensing
Univ Pittsburgh
sensing wipe
Agentase
Rice
CNT for adsorbents
CNI
NRL
nanoAu chemical
MicroSensor Systems
sensing
Auburn
CNT adsorbent media
IntraMicron Inc
ORNL
cantilever sensing
Protiveris
Tufts U.
nanoarray sensors
Illumina
Nanotechnology Innovation for CBRE: Detection and Protection
Short-Term (1-5 yr) Transition Opportunities
For transition into commercial product inside of five years, these opportunities must already have: a)
demonstrated proof-of-principle and b) existing commercial involvement. Specific examples are itemized in
Table 5.
Funding to accelerate these opportunities might come from the mission-oriented agencies such as DOD
where 6.2-6.4 monies are available for the development of new technology; the DOT Transportation Security
Administration; and the Office of Homeland Security. The NSET member agencies must also continue to
exploit the SBIR/STTR programs to accelerate commercial transitions.
Mid-term (5-10 yr) Transition Opportunities
Areas where an investment in nanoscience holds the promise for paradigm breaking approaches to
detection/protection with commercial product transition in the 5-10 year time frame are as follows:
• Sensing
Transduction/actuation mechanisms for greater sensitivity/selectivity
Biotic/abiotic interfaces to marry semiconductors with in-vivo biology
Environmental energy sources to minimize battery requirements
Incorporate separation and detection technologies at micron scales with lab-on-a-chip
• Protection
High surface area materials with templated structure for selective adsorption
Controlled porosity for selective migration and separation
Nanofibers and nanotubes for clothing with improved adsorption/neutralization of agents
Smart materials for control of diffusion and active mass transport
Smart nanoparticles that recognize and sequester or destroy specific toxins
Large scale structured packings, coatings, and other media with optimized microstructure to
enhance/accommodate key underlying transport issues
• Neutralization/Decontamination
Nanostructures to disrupt biological function
Catalytic nanostructures
• Prevention
Nanostructures to reduce or replace hazardous substances in manufacturing
Nanostructures that selectively bind and decompose hazardous substances
• Therapeutics
Encapsulated drugs for targeted release
Combination of therapeutics with imaging agents for monitoring
Intracellular drug delivery
Targeting radio and optical energy to localized sites
Bioscavengers
Nanoparticle for detoxification, e.g., chemical agents in blood
Long-term (10-20 yr) Transition Opportunities
Areas where an investment in nanoscience is important for integrating many components into a complex
system (e.g., sensor suites) or for providing sufficient insights into a complex system (e.g., cell physiology)
to enable innovative nanotechnologies include the following:
• Multifunctional surfaces
Develop surfaces that contain sensing and reactive moieties for protection, self-decontamination, and
self-sterilization
11
Nanotechnology Innovation for CBRE: Detection and Protection
• Cell-based sensing
Develop sensing technology that responds to unknown new threats by measuring the response of
living systems that mimic human biochemistry
• In-vivo diagnostics
Sophisticated, body powered, in-vivo diagnostics for identifying physiological abnormality
• NEMS
Extend microelectromechanical systems (MEMS) technologies another three orders of magnitude
smaller in order to incorporate significantly greater capability
• Laboratory on a chip
Incorporate multiple separation and detection technologies at sub-micron scales on a single chip in
order to get inexpensive rapid detection technology for all threat agents (chemical,
biological, explosive and radiological) and to minimize false positive/negative events
• Hierarchical self-assembly
Make innovative approaches to directed self-assembly in multiple dimensions viable, otherwise
incorporation of greater complexity into detection/protection systems will be overly
expensive
IIIB.
Nanoscience Opportunities for Detection: Miniaturized, Intelligent Sensors (MIS)
Vision
To develop nanoscience and nanostructures that more effectively collect and deliver samples to sensitive,
selective sensors (chemical, biological, radiological, electromagnetic, acoustic, magnetic, etc.) with
information processing electronics and communication for miniaturized, intelligent sensor suites that can
actively respond to homeland defense requirements.
MIS Homeland Defense Impact
Miniaturized, intelligent sensors that will enable important new capabilities to counter CBRE threats to
civilian and military populations include the following:
• Lighter, smaller, and highly functional systems to provide rapid detection of threats, and communication
systems with greater versatility and bandwidth will affect the performance and safety of the participants
in prevention/remediation of CBRE incidents.
• With sensing/detection/signal processing at nanometer scales, surveillance “platforms” can be
inconspicuous and sufficiently inexpensive to enable prolific coverage of enclosed spaces such as office
buildings and transportation hubs.
• Uninhabited vehicles for reconnaissance could reduce the risk to human lives.
• Personal monitors for CBRE threats, physiological fatigue, and medical applications require the linkage
of biological functions with nanostructured semiconductor devices. Small sizes will be required for a
functional system to be embedded in the body where it can detect the small changes in body chemistry
incipient to more severe problems, and can initiate corrective action. Small size will also facilitate the
incorporation of molecular phenomena (synergistic with biotic systems) into electronic devices
(presently abiotic).
MIS Program
To best exploit the opportunities, MIS requires an interdisciplinary approach to the development of
sensing/information processing, decision, and actuation. The MIS program should address the following
issues:
1.
2.
12
Sample collection and concentration
Sensing, actuation, and transduction
Transduction properties of individual nanostructures, polymers and proteins
Transduction properties of nanostructure arrays
Nanotechnology Innovation for CBRE: Detection and Protection
3.
4.
5.
6.
7.
IIIC.
Molecular machine/nanomachine concepts
Tethered nanodots/nanowires with magnetic/electric field actuation
Magnetic/electric/optical/chemical signaling
Artificial cells
Molecule – semiconductor/metal interface
The balance of bond stress and bond energy in surface reconstruction
Electron/hole transfer between molecule/biomolecule and semiconductor
Novel bonding chemistry
Biotic and abiotic interfaces
Surface compatibility of semiconductors in aqueous/physiological environment
Linkers with retention of biological function such as molecular recognition
Membrane gating
Development of functional interconnects between nanoscale building blocks
Fabrication with a focus on assembly of building blocks (i.e., nanodots, nanowires, etc.)
Techniques for patterning and fabrication of circuits with nanostructures
Hierarchical assembly of functional arrays
Directed assembly utilizing designated chemical/molecular recognition events
Nanodevices: shape, size, defects, and impurities
Methods to model and design nanostructure properties and nanodevice performance
Power sources
New methods, materials and devices to harvest energy from the environment
Ability to interconnect power sources with nanostructures and complex architectures
Molecular motors
Nanoscience Opportunities for Protection/Remediation/Prevention (PR&P)
Vision
To develop nanoscience and nanostructures which enable revolutionary advances in adsorbent materials
(personal and collective protection), separation technologies (protective clothing and filters),
neutralization/decontamination of agents, and prophylactic measures.
Homeland Defense Impact
Empirically derived nanoscaled materials have been a mainstay in CBRE protection and neutralization.
Attention to the underlying nanoscience base should lead to dramatic improvements, especially as that
knowledge enables the development of more sophisticated systems, such as:
• Decontamination via aggressive chemical systems, damaging to human and equipment as well as CB
agents, can be replaced by treatments as effective at decontamination but benign to humans and the
environment.
• Specific smart nanoparticle decontaminating agents.
• Decontamination of sensitive equipment (water not allowed).
• Protective clothing and personal protection filters that incorporate decontamination activity rather than
simple adsorption, and permit water vapor migration for cooling.
• Masks/filters with adsorbents having greater selectivity and capacity for harmful agents, incorporating
miniaturized sensing to detect breakthroughs, and potentially neutralize the agents.
• Innovative approaches to the deactivation of biological agents, especially spores.
• Manufacturing and processing industries free of hazardous materials and wastes.
• Artificial nanosystems for on-site and on-demand chemical and biological synthesis.
• Novel carrier technologies and strategies that allow emerging bulk phase nanomaterials to be placed into
large-scale structured packings, monoliths, coatings, electrodes, and other media while optimizing
overall system microstructure so as to enhance or accommodate key underlying transport issues (i.e.,
13
Nanotechnology Innovation for CBRE: Detection and Protection
heat, mass, ions, electrons, etc.) and to capitalize on the benefits provided by desirable nanomaterial
surface kinetics and selectivity.
Protection/Remediation/Prevention Program
To best exploit the opportunities, PR&P requires an interdisciplinary approach to the development of
nanostructures that selectively interact with CBRE molecules. A PR&P program should address the
following issues:
1.
2.
3.
4.
5.
6.
High-surface area, selective adsorbents
Non-carbon adsorbents
Templated surfaces for more selective adsorption
Nanotubes and nanotube membranes
Hierarchical control of porosity for low-pressure drop
Incorporation of catalytic decomposition for agent destruction
Biomolecular adsorbent/filtration materials
Catalytic materials
Proteins as biological enzymes
Tailored nanoclusters for selective catalysis and benign products
Tunable photocatalysts
Environmentally benign catalysts
Nanostructures for clothing/separators
Fabrication of polymer nanofilaments
Incorporation of catalytic centers in fibers
Fiber surface modification
Nanoporous materials
Designed nanostructured membranes
Nanostructures capable of disrupting biological agent function
Nanoemulsions
Protein and synthetic nanotubes for membrane disruption
Prophylactic nanostructures
MEMS/NEMS for drug delivery
Nanotherapeutic delivery platforms
Intracellular monitors for infection/radiation damage
Nanostructured reactors in skin creams
Nanostructured materials for wound cleansing and treatment
Low cost, high-speed manufacturing techniques that incorporate desirable bulk phase nanomaterials
into fabrics, papers, composites, covers, packaging materials, and porous media suitable for chemical
processing and mitigation applications at both the smallest and largest application levels.
IV.
Infrastructure
MEMS/NEMS fabrication facilities will be necessary to implement the sensing goals. Nano-powder and
nano-filament production scale-up will be necessary to implement the protection goals. New materials
handling technologies and modifications to existing processes will be needed to incorporate bulk phase
nanomaterials into existing manufacturing and distribution infrastructure.
It is expected that these
requirements will be met by other parts of the NNI program.
Since any new technology must ultimately be tested against real agent, access to surety test and evaluation
facilities in the Joint Chemical and Biological Defense Program must be included in this grand challenge.
This testing is expensive; adequate funding must be available.
14
Nanotechnology Innovation for CBRE: Detection and Protection
V. Recommended Investment Strategy
The workshop participants were polled for their opinions on S&T funding distribution on the basis of three
criteria:
1) the importance of technology in coping with the problems posed by CBRE protection/detection
2) the potential for nanotechnology to contribute significant improvements to that technology
3) the availability of resources and expertise ready to utilize effectively any funding increase.
1. Funding Distribution
After the group decided on the appropriate topics/subtopics to be funded, each participant independently
designated a percentage for each subtopic. The averaged distribution is reported in Table 6. The result has a
distribution of approximately 50% in sensing, 30% in protection and 20% in remediation.
Table 6
Federal Nanotechnology S&T Balance Recommended by Workshop Participants
Topic
Subtopic
Avg
Standard
(%)
Deviation
Sensing
Biological
13
6
Chemical
10
4
Radiological
6
3
Explosive
10
5
Sample Collection
4
3
Remote
3
3
Protection
Adsorption
11
5
Separation
8
4
Neutralization
13
4
Site Remediation
Biological
8
5
Chemical
8
3
Radiological
6
3
While therapeutics is clearly an important topic for CBRE S&T, the workshop participants believe the
advanced healthcare grand challenge would adequately cover this topic. Similarly, it was decided that threat
reduction by reducing the amounts of hazardous materials utilized in manufacturing, while valuable, should
be part of the manufacturing at the nanoscale and environmental grand challenges.
Table 7 shows the distribution of the FY01 investment by the NNI agencies in topics directly relevant to
nanotechnology for CBRE Protection/detection. The FY01 funding was used since FY02 funding was still
evolving at the time of this workshop. A goal of $100 million total investment by FY05 was identified as
worthwhile.
Outside of the present investment in nanotechnology for chemical and biological sensing, there are clear
program deficiencies. Further, while the discovery aspect of fundamental research is clearly crucial, the
realization of the short- and mid-term goals for technology options will require availability of growing
amounts of both applied research and SBIR funds. It is recommended that approximately one half of the
$100 million should be devoted to the explicit task of developing those options (see Table 8).
15
Nanotechnology Innovation for CBRE: Detection and Protection
Topic
Table 7
Government S&T Investment ($ millions)
Subtopic
FY01
FY05
(est)
(recom)
Sensing
Biological
Chemical
Radiological
Explosive
Sample Collection
Remote
15
13
13
10
6
10
4
3
Adsorption
Separation
Neutralization
0.5
0.5
4
11
8
13
33
8
8
6
100
Protection
Site Remediation
Biological
Chemical
Radiological
Total
Table 8
Federal S&T Investment in Nanoscience CBRE by Funding Type ($ millions)
FY01
FY02
FY03
FY04
FY05
Fundamental
31
26
35
45
55
Applied
10
20
30
40
SBIR/STTR/ATP
2
2.5
3
4
5
Total
33
100
2. Leveraging Among Participating U.S. Government Agencies and International Efforts
The CBRE grand challenge should achieve critical mass in nanoscience toward its aggressive goals by
leveraging the other NNI research programs (and other nanoscale R&D), especially the NASA programs in
microsatellites; the DOE programs in environmental sensing; the NIH programs for medical sensors and
therapeutics; the NSF programs in simulation/modeling and green manufacturing; the EPA programs in
improved sensors, treatment/remediation, and hazardous substance reduction/elimination; the DOT programs
in trace explosives detection; and the DOD programs in nanoelectronics, molecular electronics and
chemical/biological defense.
The goal of $100 million by FY05 would require about 10% of the anticipated U.S. annual NNI funding.
That is a significant fraction of the NNI investment and might be detrimental to the rate of progress toward
other grand challenge goals. The CBRE terrorist threat is not unique to the United States. It is strongly
recommended that joint international programs be developed to incorporate the excellent and extensive
European and Pacific theater nanoscience on CBRE detection and protection.
3. Cross-disciplinary and University/Government Laboratory Linkages
It is critical to integrate the biology, chemistry, engineering, materials and physics research communities to
establish the interdisciplinary nanoscience knowledge and expertise needed to exploit nanostructures in the
development of the following:
16
Nanotechnology Innovation for CBRE: Detection and Protection
• Miniaturized, real-time, intelligent, redundant sensor systems with revolutionary CBRE detection
performance
• New high-surface area templated adsorbents for personnel/collective protection and decontamination
systems, potentially incorporating catalytic reactive systems
• Nanofiber/nanoporous membranes for effective protective clothing without undue heat loading,
potentially incorporating catalytic materials to neutralize agents while remaining relatively benign to
humans and the environment
• Mechanisms to disrupt the viability of biological agents
• Multifunctional materials that recognize and generate a response to a threat agent
• Nanoscale processes that reduce or eliminate the use or production of hazardous substances
The grand challenge should strengthen the linkages between the university research communities and the
DOD/DOE/NIST laboratories where CBRE test, evaluation and systems innovation have traditionally been
performed.
4. Interagency Coordination
To maximize the rates of scientific discovery and its technology transition, this grand challenge must exploit
the traditional strengths of the NNI participating agencies/departments:
DOD
chemical/biological agent – sense/protect/mitigate/decon; landmine sense
DOE
radiological/explosive; system integration – lab-on-a-chip
DOJ/NIJ
chemical/biologic agent – sense/protect; DNA forensic analysis
DOT
explosive detection; advanced transportation security systems
EPA
chemical/biological detection; decon/neutralization; hazardous substance reduction
NASA
system integration; miniaturization; robotic systems
NIH
therapeutic treatment for chemical/biological/radiological exposure
NIST
chemical microsensors, single molecule measurement
NSF
fundamental science underpinnings
State/Intel
detection for treaty verification and non-proliferation
Coordination amongst many of these agencies at the technology level already happens through the Technical
Support Working Group (TSWG). The estimated FY 01 nanoscience investment levels are shown in
Table 9.
Table 9
FY01 Agency Investment in Nanoscience/Nanotechnology Relevant to
CBRE Protection/Detection ($ thousands)
Topic
Sensing
Subtopic
Biological
Chemical
Radiological
Explosive
Sample Collection
Remote
DOD
DOE
DOT
EPA
NASA
NIH
NIST
NSF
Totals
7.5
6.6
7
5.5
14.9
12.5
1
0.5
0.4
1.8
0.5
0.4
4.4
Protection
Adsorption
Separation
Neutralization
Remediation
Biological
Chemical
Radiological
1.6
17
Nanotechnology Innovation for CBRE: Detection and Protection
The grand challenge should couple closely with existing programs that address the CBRE threat, especially
19
the DOD Joint Service Chemical and Biological Defense Program , the Defense Threat Reduction Agency,
the Interagency Technical Support Working Group (TSWG, http://www.bids.tswg.gov), the DOE
Radiological and Environmental Protection Program, and the DOT Weapons and Explosives Detection
Program (aviation). The NNCO should approach these agencies to solicit further guidance for the best
investment strategy, and to engage agency interest/funding in the recommended applied research efforts.
This involvement will ameliorate the “not-invented-here” syndrome that frequently stifles technology
transition.
VI.
Conclusion
It is clear that nanotechnology has the potential to dramatically ameliorate the problems associated with
terrorist use of chemical, biological, explosive and radiological threats. The development of a broad range of
new, sensitive, selective, nanotechnology-based sensors for chemical, biological and explosive threats is
imminent. Miniaturization enabled by the nanoscale offers opportunities for integrating sensor capabilities
and detecting all four of the threat classes with a single, low power, handheld unit. The high surface-tovolume ratio for nanostructures will also lead to dramatic improvements in protection and remediation. For
example, nanostructures are key components in cellular physiology, and nanoscience is already providing
new insights into the disruption of bacterial agent physiology. The recommend funding goal for
nanotechnological approaches to CBRE is $100 million by FY05, distributed as 50% in sensing, 30% in
protection and 20% in remediation. The present investment is approximately $30 million and is mostly
focused on sensing. There are nanotechnology opportunities for the short, mid and long range. In addition to
funding fundamental research, there should be growing funds for applied research with the goal of roughly a
50/50 mix by FY05.
19
“Department of Defense, Chemical and Biological Defense Program, Annual Report to Congress,” March 2000;
DTIC ATTN: DTIC-E (Electronic Document Project Officer), 8725 John J. Kingman Road, Suite 0944, Fort Belvoir,
VA 22060-6218.
18
Nanotechnology Innovation for CBRE: Detection and Protection
Appendix A: Evolving Nanotechnology Success Stories Pertinent to CBRE
A.1. Nanoparticles for Chemical and Biological Agent Decontamination
Decontamination and destruction of chemical and biological warfare agents in the field is of great importance
to the warfighter. New reactive adsorbents for the removal of toxic materials and chemical warfare agents
are a priority need for the Army. The Army Research Office has been supporting Professor Kenneth
Klabunde at Kansas State University to study the fundamental chemistry of nanoparticles for several years
now. Nanoparticles are very small particles with increased surface area and reactivity. One-quarter ounce of
nanoparticles has the same surface area as a football field.
Figure A.1. Powdered sorbent being used to decontaminate a soldier.
Certain nanoscale particles are reactive in neutralizing both chemical and biological agents. Methods to
disperse the nanoparticles via mitts (like the M-295 Immediate Decon Kit or Sorbent Decontamination
System, Figure A.1) or sprayers (like the M-11, Figure A.2) are underdevelopment. The nanoparticles are
currently being evaluated by the U.S. Army Edgewood Chemical Biological Center, U.S. Army Medical
Research Institute for Chemical Defense, Natick Solider Center, Dugway Desert Test Center, and the
Defense Evaluation and Research Agency of the United Kingdom.
19
Nanotechnology Innovation for CBRE: Detection and Protection
Figure A.2. Powdered sorbent being sprayed from a device
similar to the M-11 sprayer.
Nanocrystals of Al2O3 and Al2O3/MgO have been produced by an alkoxide based synthesis involving the
corresponding aluminum tri-tert-butoxide, magnesium methoxide, toluene, methanol, ethanol, and water.
The resulting oxides are in the form of powders having crystallites of about 2 nm or less in dimension.
These crystallites have been studied by transmission electron microscopy (TEM), and Brunauer-EmmetTeller (BET) methods, and were found to possess high surface areas and pore volumes (800 m2/g for Al2O3,
790 m2/g for Al2O3/MgO, compared to 450 m2/g for MgO). As seen with other metal oxides, once they are
made as nanoparticles their reactivity is greatly enhanced on a per unit surface area basis. This is thought to
be due to morphological differences, whereas larger crystallites have only a small percentage of reactive sites
on the surface, smaller crystallites possess much higher surface concentration of such sites per unit surface
area. Reactions with CCl4, SO2, and paraoxon have demonstrated significantly enhanced reactivity and/or
capacity compared with common commercial forms of the oxide powders. An important finding is that the
combination of Al2O3 and MgO allows for unexpectedly high surface areas and with a combination of Lewis
acid and Lewis base character. The results show: a) intermingling has enhanced reactivity/capacity, over the
pure forms of nanoscale Al2O3 or MgO, toward chemical warfare surrogates (paraoxon) and an acid gas
(SO2); and b) tailored synthesis of a nanoparticle formulation can yield special benefits, and demonstrates
just one example in thousands of possibilities.
Table A.1
Examples of Enhanced Capacities of Intimately Intermingled Nanoscale Moieties of Al2O3 and MgO
Sample
Total molecules of SO2
adsorbed per nm2 of
nanoparticle oxide
mmoles paraoxon destructively
adsorbed by one mole nanoparticle
oxide
MgO
6.0
22
Al2O3
3.5
91
Al2O3 /MgO
6.8
180
References
(1) Corrie Carnes, Ph.D. Thesis, Kansas State University, 2000.
(2) C. L. Carnes, P. N. Kapoor, K.J. Klabunde, and J. Bonevich, Chem. Materials 14(7), 2922-2929 (2002).
20
Nanotechnology Innovation for CBRE: Detection and Protection
A.2. Nanoparticles for Sensitive, Selective Detection of CBRE agents
The analytical tools being developed for nanoscience must locate and measure the properties of single atoms.
This precision can be adapted to sensing with exquisite sensitivity. Several sensor concepts are under
commercial development for chemical and biological agent detection. As an example of chemical sensing,
organothiol stabilized nanosized Au clusters have been self-assembled between two microfabricated
electrodes. The current flowing between the electrodes depends on electron tunneling through the organic
films. Small amounts of chemical agents in the air surrounding the sensor can partition into the organic and
cause changes in its dimension or dielectric constant (1). Both effects cause exponential changes in electrical
current; parts-per-billion of chemical agents have been detected by this approach. Utilizing pattern
recognition techniques, an array of sensors – each with a different organic constituent – provides the
selectivity. This technology is under commercial development by MicroSensor Systems Incorporated
(Figure A.3). As an example of biological sensing, it has been shown that nanosized Au clusters in solution
have different colors, depending on their separation. If appropriately chosen strands of DNA are attached to
the clusters, the presence of its complement can cause the clusters to be “glued” together and change color.
A lower detection limit for this system has been demonstrated of 500 pM for a 24 base single-stranded target
and 2.5 nM for a duplex target nucleotide (2). It has been shown that anthrax DNA can be sensitively
detected by this technique; commercial development is underway by Nanosphere Inc. (Figure A.4).
Fig. A.3. MicroSensor Systems Inc.
handheld chemical sensor based
on nanoparticle Au (1).
Fig. A.4. Color change in Au nanoparticles
localized by DNA sequence
recognition (2).
References
(1) “Colloidal metal-insulator-metal ensemble chemiresistor sensor,” H. Wohltjen and A.W. Snow
Analytical Chemistry 70, 2856-2859 (1998); “Gold nanocluster vapor sensors,” A.W. Snow, H.
Wohltjen, and N. L. Jarvis, Abst of Papers at the American Chemical Society 221: 324-IEC, Part 1 Apr 1,
2001.
(2) “A gold nanoparticle/latex microsphere-based colorimetric oligonucleotide detection method,” R.A.
Reynolds, C.A. Mirkin, and R.L. Letsinger, Pure and Applied Chemistry 72, 229-235 (2000);
“Homogeneous, nanoparticle-based quantitative colorimetric detection of oligonucleotides,” R.A.
Reynolds, C.A. Mirkin, and R.L. Letsinger, J. Am. Chem. Soc. 122 (15), 3795-3796 (2000).
21
Nanotechnology Innovation for CBRE: Detection and Protection
A.3. Microcantilevers: An Ideal Sensor Platform for Terrorist Threat Detection
A widespread need exists for portable, real-time, low-power, in-situ sensors for detection of terrorist threats
such as nuclear radiation, biological and chemical warfare agents (BCW), and explosives. Unfortunately,
most sensors developed to date have been limited in detection ability and the number of components that can
be sensed. These limits may be alleviated soon with the advent of microcantilever sensors. The key
operative factors for microcantilever sensors are simplicity, extreme high sensitivity, low cost and
modularity.
Microcantilevers are the simplest microelectromechanical systems (MEMS) (shown in Figure A.5) that can
be micromachined and mass-produced using conventional techniques. The unprecedented sensitivity of
microcantilever physical, chemical, and biological sensors, as demonstrated many laboratories around the
world, suggests that in the years to come, microcantilever sensors will be an integral part of many sensor
devices. Microcantilever resonance response such as resonance frequency, deflection, and Q-factor undergo
variation due to extremely small changes in external stimuli. Cantilever geometry determines sensitivity
while selectivity is governed by the analyte-substrate interaction mechanism. The advantages of
microcantilever sensors include extreme high sensitivity, selectivity, and wide dynamic range. Demonstrated
examples include detection of ricin, nerve gas simulants, alpha particles, and explosive vapors such as TNT,
RDX, and PETN. It is possible to arrange arrays of microcantilevers on one single chip for multi-target and
multi-threat detection.
Figure A.5. Microcantilevers.
References
(1) “Microcantilever sensors,” T. Thundat, et al., Microscale Thermophysical Engineering 1(3) 185, (1997).
(2) “Bioassay of prostate specific antigen (PSA) using microcantilevers,” G. Wu, et al., Nature
Biotechnology, 19, 856-860, (2001)
(3) “A chemical sensor based on a microfabricated cantilever array with simultaneous resonance frequency
and bending readout,” F.M. Battiston et. al., Sensors and Actuators B77(1-2), 122-131 (2001).
(4) “Microcantilever charged-particle flux detector,” A.D. Stephan, T. Gaulden, A.D. Brown, M. Smith, L.F.
Miller, and T. Thundat, Rev. Sci. Instrum. 73(1), 26-41 (2002).
22
Nanotechnology Innovation for CBRE: Detection and Protection
A.4. Application of Nanomaterials to High Rate Mitigation of ChemBio Threats
Chemical reactions occurring at the nanoscale continuously affect all aspects of life and technology as we
know it. Nanostructured materials are fundamental building blocks capable of catalyzing a host of chemical
reactions by virtue of their selective and tailored surface chemistries, high specific surface areas, and unique
molecular structures.
Recent discoveries have enabled the entrapment of nano- and microstructured materials within the interior of
high porosity carrier networks comprised of sinter-locked micron diameter metal fibers (see Figure A.6a).
This discovery greatly extends the impact and utility of evolving nanotechnologies to an ever increasing
variety of chemical processes. A low cost, high-speed paper making process is used to produce the materials
shown in Figure A6a, while the volume fraction of the metal microfibrous carrier phase and the solid reactant
phase can both be varied over a wide range (independent of one another). In this manner, chemical reactions
occurring at the surface of the entrapped phase are accommodated within a carrier of sufficient porosity to
support required heat and mass transport to the reactive surface. This attribute is not presently available by
other means, and appropriately selected nanomaterials coated onto the surface and within the pores of the
entrapped phase yield sustainable reaction rates significantly higher than ever previously imagined or
commercially practiced. High volumetric reaction rates have been demonstrated for: surface catalyzed
reactions, electrochemical systems, sorption processes, electrochemically assisted biological growth,
filtration processes, and thermal wicking systems.
For applications in chemical and biological mitigation, microfibrous entrapped nanostructures have been
demonstrated to provide two- to four-fold higher adsorption efficiencies at as little as one-eighth the pressure
drop of a comparable packed bed of the identical sorbent. The thin layer nature of this media is also wellsuited for new applications such as: foldable, pocket size chemical/biological escape hoods (see Figure
A.6b); higher capacity lower pressure drop gas mask canisters (see Figure A.6c); and TSA regenerable
sorbent canisters for continuous protection of buildings and structures (see Figure A.6d). Regeneration is key
to reducing life-cycle, logistical, and ownership costs. Regeneration also permits significant decreases in
weight and volume, which enables extension of this technology to aircraft and transportation systems.
Figure A.6:
a. microfibrous entrapped
sorbent and catalyst
canister
b. Low pressure drop, foldable c. C1A1 & microfibrous
pocket size escape hood
pleated canisters
d. Collective protection
sorbent/catalyst
References
(1) “Permeability of sintered microfibrous composites for heterogeneous catalysis and other chemical
processing opportunities,” D. R. Cahela and B. J. Tatarchuk, Catalysis Today 69(1-4), 33-39 (2001).
(2) “Wet layup and sintering of metal-containing microfibrous composites for chemical processing
opportunities,” D. K. Harris, D. R. Cahela, and B. J. Tatarchuk, Composites: Part A 32, 1117-1126
(2001).
23
Nanotechnology Innovation for CBRE: Detection and Protection
A.5. Nanostructured Films for Chemical Sensing
Chemical microsensors have been developed consisting of nanoparticle oxide sensing films on MEMS
device platforms. While the platforms provide necessary functionality for controlling the sensors and
extracting response signals, the heart of each microsensor is its approximately 100- 500 Å thick (SnO2, TiO2)
sensing film, which directly interacts with the environment being monitored. The devices operate by
measuring the changes in electrical conductance that occur when gases adsorb, desorb and/or react at the
surfaces of the semiconducting oxide films. Rapid temperature modulation can be used to increase the
analytical information acquired per unit time. The roughly 100 µm x 100 µm devices (Figure A.7) can be
fabricated in array configurations that are tunable for different applications through the choice of sensing
materials and operating temperatures. Due to their small size, the power consumption for the microsensors is
very low.
Sensing characteristics such as sensitivity, selectivity, stability and speed are inherently dependent on the
nanostructural features of the sensing films used in the microsensors. Particle size and surface structure
strongly affect both the chemisorption and electronic properties of the films. Nanostructured oxides must be
deposited onto the SiO2 top surface of the MEMS microelements (see Figure A.7). Localized deposition of
controlled microstructures on these 3-dimensional devices does present significant fabrication challenges.
However several methods, including seeded, reactive chemical vapor deposition (CVD), single source CVD
(Figure A.8), and spinning on of sol-gels and nanoparticle suspensions, produce effective sensing oxides with
particle sizes ranging from about 10 - 100 nm. Generally, the finer films show higher sensitivities.
Application-oriented efforts supported by several agencies have demonstrated the capabilities of the
conductometric microsensors in a variety of areas. Combinatorial microarray methods were employed in a
Department of Energy (DOE) project targeted at detection of hazardous waste. An “emerging technology”
project supported by the Defense Threat Reduction Agency (DTRA) has demonstrated the ability of the
microsensors in detecting low levels of molecules that simulate mustard and nerve class chemical warfare
agents. It is anticipated that other nanostructured materials (wires, tubes, etc.) will enhance sensor
performance by producing new types of sensing effects as well as serving in new functional roles, such as
filters and preconcentrators, for microsensor-based microanalytical systems.
Fig. A.7. MEMS microsensor platform
with CVD oxide sensing film.
Fig. A.8. SEM micrograph of TiO2 film grown
by CVD from titanium nitrate.
References
(1) “Microhotplate platforms for chemical sensor research,” S. Semancik, R.E. Cavicchi, M.C. Wheeler, J.E.
Tiffany, G.E. Poirier, R.M. Walton, J.S. Suehle, B. Panchapakesan, and D.L. DeVoe, Sensors and
Actuators B 77(1-2), 579-591 (2001).
(2) “Nanoparticle engineering and control of tin oxide microstructures for chemical microsensor
applications,” B. Panchapakesan, D.L. DeVoe, M.R. Widmaier, R. Cavicchi, and S. Semancik,
Nanotechnology 12(3), 336-349 (2001).
24
Nanotechnology Innovation for CBRE: Detection and Protection
A.6. Rapid Development of Sensors for the Detection of Weapons of Mass Destruction
Computational methods for the redesign of the ligand-binding specificity of receptor proteins that can
function as fluorescent, electrochemical or cellular biosensors have been developed and experimentally
tested. The ultimate aim is to radically redesign a binding site for any ligand within a certain molecular
weight range, and to apply this capability to the construction of robust, reagentless biosensors for the
continuous, real-time detection of explosives and chemical and biological warfare agents. The combined
computational and experimental methodologies provide a revolutionary capability to design, construct and
deploy sensors for newly identified threats within 7-10 days.
The computational methods use the three-dimensional structure of a protein to redesign its ligand-binding
site. An ensemble of ligand conformations are docked in place of the original ligand, and simultaneously
replace the amino acids at each of the 15-20 positions that define complementary surfaces with the
approximately 9000 rotamers representing all 20 possible mutations. A receptor design calculation then
identifies the best combination of docked ligand and amino acid sequence to create a new complementary
surface. Algorithms have been developed that can solve this huge combinatorial problem (often 10100-10200
possible combinations) within 48 hrs on a 25-processor Beowulf cluster. (Time is linear with number of
processors.)
The periplasmic binding proteins of E. coli as the receptors are soluble, very robust, monomeric proteins that
bind a wide variety of ligands. Using novel computational methods, radically redesigned members of this
protein superfamily have been shown to bind trinitrotoluene, or lactate, resulting in sensors that detect these
analytes. The TNT sensor has a 1.5 nM affinity. These results demonstrate that with this new approach it is
possible to radically redesign binding specificity, and that one can attain binding sites with both a high
degree of steorespecificity and very high-affinity. The detection limit is probably better than nanomolar;
experiments are under way to establish this.
The design cost for each sensor is low: ~$200/design in oligonucleotides and reagents (not accounting for the
computational and experimental laboratory infrastructure). Once built, the biosensor proteins are
inexpensive to produce. Bacterial over-expression systems will easily provide 50 mg/L for less than $20.
Fluorophores necessary to label this amount of protein cost $100-300. 50 mg is more than enough protein
for incorporation into hundreds of sensor units (e.g., at the tip of optical fibers).
Receptor
TNT
Redesigned
binding
surface
Figure A.9. Receptor protein sensor concept.
Reference
(1) “Converting a maltose receptor into a nascent binuclear copper oxygenase by computational design,”
D.E. Benson, A.E. Haddy, and H.W. Hellinga, Biochemistry 41(9), 3262-3269 (2002).
25
Nanotechnology Innovation for CBRE: Detection and Protection
A.7. Non-Invasive Monitoring of Cells for the Diagnosis of Pathogen Exposure and Infection
Nanotechnology could provide a biosensor that would be loaded into the white blood cells of soldiers. This
biosensor would measure the activation of leukocytes and identify early non-specific events associated with
exposure to pathogens, such as alterations of mitochondrial calcium mobilization or superoxide production.
In addition, the sensor would also identify events such as cytokine expression in white cells that differentiate
an infection with a specific class or type of organism. These signals would be monitored non-invasively
using laser light directed at a laminar-flow stream of blood cells in a capillary. The system would function
like a real-time flow cytometer, but without the need for equipment, blood drawing or sample preparation.
This approach is unique in that it will use nanosensors based on dendritic polymers. These sensors are less
than five nanometers in diameter, and are targeted to white cells by molecules attached to their surface to
specifically bind and internalize into leukocytes. These biosensors employ non-toxic, fluorescent reporter
systems. When these sensors are delivered into a cell and activated by the appropriate cellular change, they
produce fluorescence emissions that can be interrogated by light shining on a capillary. Multispectral
analysis will allow the use of multiple sensors using dyes with different wavelength emissions. Importantly,
these biosensors need to be given only once every few weeks to maintain their presence in cells, and might
even be administered transdermally to avoid venous injections. The sensors have almost no mass and, since
they would be located within the soldier’s cells, would avoid the need for storage.
The concept of this intracellular biosensor system in vitro
would adapt a miniaturized laser system for use as a
wearable monitor to non-invasively read sensor output
from capillaries in real time. This laser would analyze the
laminar blood flow of either a retinal or a mucosal tissuebased capillary to non-invasively sense the white cell
population in vivo as these cells pass through the capillary.
The fluorescent signals can be sensed specifically because
the white blood cells pass through capillaries one at a time
in a laminar stream, and retinal capillaries can be
interrogated without optical interference from tissues or
hemoglobin.
The sensing apparatus (Figure A.10) would involve a
miniaturized optic probe placed in a “head’s up display” to
shine light onto the retina, or alternatively by using a fiber
optic placed under the tongue and worn continuously for
monitoring. A monitoring station also could be used where
Figure A.10. Illustration of the concept of
the individual would immobilize his or her head for a
an optic probe-based
retinal scan that would allow a laser light to raster several
monitoring system.
capillaries simultaneously. Either type of monitor would
be non-invasive, and could accomplish real time
monitoring, making the system useful for identifying changes in white cell population kinetics as well as the
actual activation of specific genes over time.
This interesting concept has been proposed by Dr. James R. Baker, Jr. of the University of Michigan.
26
Nanotechnology Innovation for CBRE: Detection and Protection
Appendix B: Glossary of Acronyms
AC
ASH/SLASH
ATP
CBRE
CBW
CK
CNT
DMMP
DNA
DS2
GA
GB
GD
GF
HD
HEPA
HN-3
L
LD50
MEMS
MIS
MOPP
NBC
NEMS
NNI
NRL
NSET
ORNL
POL
PR&P
R&D
S&T
SBIR
STTR
TEDA
TGD
TIC
TSWG
VX
blood agent, hydrogen cyanide
Activated solution hypchlorite/self-limiting
Advanced Technology Program (DOC/NIST)
Chemical, biological, radiological and explosive
Chemical and biological warfare
blood agent, cyanogen chloride
Carbon nanotube
Dimethyl, methyl phosphonate – simulant for G chemical warfare agents
Deoxyribonucleic acid
Decontaminating Solution 2 [diethylenetriamine, ethylene glycol,
monomethylether, sodium hydroxide]
nerve gas, tabun, dimethlphosphoramidocyanidate acid, ethyl ester
nerve gas, sarin, methylphosphonofluoridic acid 1-methylethyl ester
nerve gas, soman, methyphosphonofluoridic acid 1,2,2-trimethypropyl ester
nerve gas, cyclohexyl sarin
distilled mustard, vesicant, bis (2-chloroethyl) sulfide
High efficiency particulate air (filter)
blister agent, 2.2.2-trichlorotriethylamine
blister agent, Lewisite [dichloro (2-chlorovinyl) arsine]
lethal dosage to 50% of population
Microelectromechanical system(s)
Miniaturized intelligent sensing
Mission oriented protective posture
Nuclear, biological, chemical
Nanoelectromechanical system(s)
National Nanotechnology Initiative (U.S. Government)
Naval Research Laboratory
Nanoscale Science, Engineering and Technology (subcommittee of U.S.
National Science and Technology Council)
Oak Ridge National Laboratory
Petroleum, oil and lubricants
Protection, remediation and prevention
Research and development
Science and technology
Small Business Innovative Research Program, U.S. Government
Small Business Technology Transfer Program, U.S. Government
Triethylenediamine
Thickened GD
Toxic industrial compounds
Technical Support Working Group (U.S. Government interagency group)
Nerve gas, ethyl S-2-diisopropyl aminoethyl methylphosphorothiolate
27
Nanotechnology Innovation for CBRE: Detection and Protection
Appendix C: List of Participants and Other Contributors
James R. Baker
9220C MSRB III
1150 W. Medical Center Dr.
Ann Arbor, MI 48109-0648
Richard J. Colton
Naval Research Laboratory
Code 6170
Washington, DC 20375-5342
Heidi Schreuder-Gibson
U.S. Army Natick Soldier Center
Kansas St. (AMSSB-RSS-MS-N)
Natick, MA 01760-5020
Michael Gr¸ nze
University of Heidelberg
Im Neuenheimer Feld 253
D-69120 Heidelberg
Germany
Kenneth J. Klabunde
105 Notre Dame Circle
Manhattan, KS 66503
Stephen Lee
Army Research Office
4300 South Miami Blvd.
P.O. Box 12211
Research Triangle Park, NC 27709
28
Charles Martin
University of Florida
Department of Chemistry
CLB 218, P.O. Box 117200
Gainesville, FL 32611-7200
James S. Murday
Naval Research Laboratory
Code 6100
Washington, DC 20375-5342
Thomas Thundat
Oak Ridge National Laboratory
Oak Ridge, TN 37831-6123
Bruce Tatarchuk
Dept of Chem Engineering
Auburn Univ
Auburn, AL 36849
Keith Ward
Office of Naval Research
Code 342
800 N. Quincy St.
Arlington, VA 22217-5660