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A02-060 TITLE: Noninvasive, Real-time Imaging of Inducible Nitric Oxide Synthase (iNOS) Activation TECHNOLOGY AREAS: Biomedical OBJECTIVE: To develop a transgenic mouse prototype for noninvasive imaging of inducible nitric oxide synthase (iNOS) activation for use in physiological experiments relevant to combat casualty care issues (e.g., hemorrhage, resuscitation, ischemia/reperfusion, etc.). DESCRIPTION: Induction of inducible nitric oxide synthase (iNOS) has been demonstrated in a wide variety of pathological states; the resulting increases in nitric oxide (NO) may have profound physiological effects to produce vasodilation and, either directly or indirectly through peroxynitrite formation, tissue injury (1-3). NO formation in this manner has been implicated in contributing to the hypotensive states associated with hemorrhage, sepsis, and anaphylaxis. Because of this, the pathological effects resulting from iNOS activation have been a source of intense inquiry, with the hope that pharmacological manipulations of this enzyme and its product might ultimately provide beneficial effects in patients. Recently, technology has become available for noninvasively imaging luciferase expression markers in vivo; this technology allows repeated visualization of gene activation in real-time within a single animal, thereby improving upon other methodologies for quantifying gene expression that require invasive sampling, such as Northern blots (4). The current effort will develop a transgenic mouse prototype that includes both a luciferase (luc) and green fluorescent protein (GFP) construct under the control of iNOS regulatory elements. In addition to allowing noninvasive visualization via the luciferase expression, GFP will also allow microscopic determination of expression levels in tissues and cells. Requirements for this transgenic mouse prototype include: 1) native iNOS expression must not be disrupted; 2) standard laboratory strains of mice must be used; 3) mice must have viability and fecundity equivalent to the parental strain when homozygous for the iNOS-luc-GFP construct; 4) genetic construct must be stably integrated and inherited with dominant expression; and, 5) construct must include eukaryotic luc genes as well as eukaryotic codon-optimized GFP tag. PHASE I: Develop iNOS-luc-GFP construct in a shuttle vector and demonstrate inducible expression in a mammalian cell line. Successful completion of Phase I will result in demonstration that iNOS-luc-GFP expression in response to known inducers of iNOS (e.g., cytokines, etc.) temporally matches iNOS mRNA expression. PHASE II: Develop transgenic mouse prototype that includes a chromosomal insertion of the iNOS-luc-GFP construct described above. Requirements for this transgenic mouse prototype include: 1) native iNOS expression must not be disrupted; 2) standard laboratory strains of mice must be used; 3) mice must have viability and fecundity equivalent to the parental strain when homozygous for the iNOS-luc-GFP construct; 4) genetic construct must be stably integrated and inherited with dominant expression; and, 5) construct must include eukaryotic luc genes as well as eukaryotic codon-optimized GFP tag. PHASE III POTENTIAL COMMERCIAL MARKET: Because of the high level of interest in iNOS as a potential mediator for physiological and pathological processes, a commercially-available transgenic mouse prototype would be a highly-sought commodity not only for government, commercial, and academic laboratories involved in combat casualty care research, but also for a wide variety of laboratories seeking: 1) to understand the basic physiology underlying such widespread diseases as stroke, myocardial infarction, and sepsis; and, 2) speed the development of new drugs and other treatments for heart disease and stroke, the number 1 and number 3 killers of Americans. REFERENCES: 1) Alderton, W. K., C. E. Cooper, and R. G. Knowles. Nitric oxide synthases: structure, function and inhibition. Biochem. J. 367: 593-614, 2001. 2) Szabo, C. and T. R. Billiar. Novel roles of nitric oxide in hemorrhagic shock. Shock 12: 1-9, 1999. 3) Szabo, C. The pathophysiological role of peroxynitrite in shock, inflammation, and ischemia-reperfusion injury. Shock 6: 79-88, 1996. 4) Wu, J. C., G. Sundaresan, M. Iyer and S.S. Gambhir. Noninvasive optical imaging of firefly luciferase reporter gene expression in skeletal muscles of living mice. Mol Ther 4: 297-306, 2001. KEYWORDS: inducible nitric oxide synthase, luciferase, transgenic, mouse A02-061 TITLE: Terahertz Interferometric Imaging Systems (TIIS) for Detection of Weapons and Explosives TECHNOLOGY AREAS: Sensors OBJECTIVE: To develop and demonstrate a terahertz-frequency imaging array with sufficient spatial and spectral resolution to enable the rapid and effective detection of concealed weapons and explosives. The envisioned sensing system will provide real-time imaging with adequate sensitivity for the short-range remote interrogation of objects and persons that might be concealing either weapons or explosives. Here, a complete source and detector technology will be developed and integrated with spectral data analysis methodologies to enable imaging across the THz frequency band (i.e., ~ 0.3 to 10 THz). DESCRIPTION: Recent events have explicitly demonstrated the serious threat that terrorist attacks present to both the private and military sectors. Furthermore, these same events have clearly articulated the need for effective measures to screen for both weapons and explosives. Hence, there presently exists a very important need to identify and develop methods for the rapid and effective detection of such threats so as to provide protection to airports, government buildings, military bases, ships, etc. Recent research has demonstrated that the transmission and reflectivity properties of materials within the terahertz (THz) frequency regime are dependent on their microscopic properties and specific chemical makeup. Hence, THz frequency spectroscopy is a potential tool for the wireless interrogation of objects and can provide for the short-range probing of nonconductive containers or clothing. The effective utilization of this detection method will require THz systems that can image with high spatial resolution and a wide field of view to enable an effective contrasting capability. Therefore, there is a strong motivation to develop and demonstrate an interferometric imaging array system that will provide the required spatial and spectral resolution. The envisioned system should be able to resolve objects down to 1 cm in size, have a ranging capacity of a few meters and possess a spectral bandwidth over the approximate frequency range 0.1 to 1 THz. This system should be developed such that it incorporates data analysis algorithms and there should be parallel efforts made to collect signature information for a set of expected targets and concealment materials. PHASE I: Conduct a comprehensive analysis and design phase of an imaging interferometer array that is capable of the remote measurement of reflection and transmission of target objects at frequencies within the range 0.1 to 1 THz. Develop data analysis algorithms that can be used towards contrasting spectral signatures taken from explosives and metal weapons concealed within nonconductive containers and clothing materials. This work should also include a laboratory-based experimental study of target agents and expected interferent agents for the purpose of developing a database of the required THz-frequency spectral signatures. This initial phase should present a complete system design and report on expected performance for the detection of specific weapons and explosive materials. PHASE II: Develop and demonstrate a prototype imaging interferometer array for the remote imaging of concealed weapons and explosives. Plan, coordinate and execute real-time field testing of the prototype system that test the spatial resolution, sensitivity, and spectral discrimination capability. PHASE III DUAL USE COMMERCIALIZATION: The technologies developed under this topic will have future applications in the commercial and military markets. The imaging technology developed under this topic will augment and extend existing efforts that utilize THz-frequency spectroscopy for the detection, identification and interrogation of chemical and biological agents. Specifically, the imaging interferometer developed under this program will provide for a new class of imaging spectrometers that can be used to rapidly monitor for chemical/biological agent emission as is needed in many industrial applications. This spectroscopic technique can also be applied for the electromagnetic probing of high-speed processes that occur in materials and devices. This capability will have commercial ramifications in areas such as semiconductor materials characterization and medical diagnostics of cells and tissue. This same technology will have duel use in military applications such as point and standoff detection of chemical and biological agents and contribute to the enhancement of satellite communications and imaging systems. REFERENCES: (A02-061) 1) C. Wichaidit, J. R. Peck, L. Zhang, R. J. Hamers, S. C. Hagness, and D. W. van der Weide, "Resonant slot antennas as transducers of DNA hybridization: a computational feasibility study," presented at IEEE MTT-S International Microwave Symposium, Phoenix, AZ, 2001. 2) D. W. van der Weide, K. Taylor, J. Peck, C. Wichaidit, S. Hagness, W. Cai, and R. Hamers, "Biomolecular contrast mechanisms and sensing techniques in the terahertz regime," presented at 9th International Conference on Terahertz Electronics, Charlottesville, 2001. 3) K. Taylor and D. W. van der Weide, "Microwave assay for detecting protein conformation in solution," presented at Photonics Boston, Boston, 2001. 4) K. Taylor and D. W. van der Weide, "Sensing folding of solution proteins with resonant antennas," presented at 9th International Conference on Terahertz Electronics, Charlottesville, 2001. 5) D. W. van der Weide, "Wideband terahertz sensing and spectroscopy with electronic sources and detectors," in Terahertz sources and systems, vol. 27, NATO Science Series, R. E. Miles, P. Harrison, and D. Lippens, Eds. Dordrecht, The Netherlands: Kluwer Academic Publishers, 2001, pp. 301-14. 6) D. W. van der Weide, J. Murakowski, and F. Keilmann, "Gas-absorption spectroscopy with electronic terahertz techniques," IEEE Transactions on Microwave Theory and Techniques, vol. 48, pp. 740-3, 2000. 7) D. W. van der Weide, J. Murakowski, and F. Keilmann, "Spectroscopy with electronic terahertz techniques," presented at EurOpto '99, Munich, 1999. 8) D. W. van der Weide, F. Keilmann, V. Agrawal, and J. Murakowski, "Gas absorption spectroscopy with electronic terahertz techniques," presented at Sixth International Conference on Terahertz Electronics, Leeds, UK, 1998. KEYWORDS: Terahertz frequency sensing, imaging arrays, explosives and weapons detection A02-062 TITLE: Portable Laser Induced Breakdown Spectroscopy (LIBS) Sensor for Detection of Biological Agents TECHNOLOGY AREAS: Chemical/Bio Defense OBJECTIVE: To develop a portable Laser Induced Breakdown Spectroscopy (LIBS) sensor for detection of various biological agents. A broadband LIBS approach will be utilized for this topic wherein the sensor will capture the full 200-940 nm spectral range per laser microplasma event. This will allow for the possible detection of all biological agents since all constituent elements emit in this spectral range. DESCRIPTION: The LIBS sensor technology is growing rapidly with an increasing number of military and civilian applications. LIBS has many attributes including: (1) no sample preparation, (2) very high sensitivity (only nanogram or less of sample required to produce usable spectrum), (3) LIBS sensors can be made rugged and field-portable, and (4) LIBS sensors are capable of point, standoff, and remote detection (using optical fibers). Recent developments in LIBS component technology, particularly in the introduction of broadband spectral detector capabilities (e.g., multiple spectrometers, echelle spectrographs) has opened up many new applications for LIBS field analyses where now molecular and biological detection and identification is possible. In fact, since LIBS readily converts the sample into its elemental constituent components, and all elements emit in the 200-940 nanometer range, LIBS is thus, in principle, capable of detecting all unknown samples. LIBS shows the potential as an important component of a multitechnology detector for reliable detection of chemical and biological agents. PHASE I: The application of LIBS to biological agent detection represents possibly the biggest current challenge for LIBS sensor technology. The most important question that has to be answered is: how unique are the LIBS spectra from different classes of bio agents such as bacteria, viruses, etc.? In the best case scenario, the broadband LIBS sensor can easily and directly distinguish between the various bio agents. However, if this is not achievable, then a secondary approach would be to incorporate a pre-selection step and then to present the product of this step for LIBS analysis. Thus, this latter approach would introduce a step of sample preparation, and therefore would require additional time for the analysis. Nevertheless, if this extra time were minimal, and the sample preparation step was straightforward and added minimal cost, then the overall approach would still be of interest to the US Army. Phase I work will demonstrate and evaluate broadband LIBS for direct biological agent detection, as well as develop new sample preparation strategies and approaches to improve the sensitivity and selectivity of the LIBS sensor. Appropriate biological agent simulants should be the focus of the Phase I work. The identification of classes is biological agents is critical with the potential to identify individual species a goal. PHASE II: In this phase a fully portable LIBS system will be built and tested for bio agent detection. It will include the development of chemometric software for instantaneous analysis of LIBS spectra through comparison with standard spectral tables as well as with a library of laboratory LIBS spectra recorded for a wide range of materials. If it is determined in Phase I that a sample preparation step is necessary, then this approach will be further refined to maximize the field use of the LIBS sensor for bio agent application. The software will provide the means to correct for matrix and temperature effects in order to maximize the quantification of the LIBS sensor. The fully man-portable system will consist of the battery-powered spectral analysis unit combined with the hand-held probe thus allowing for the detection and identification of a wide range of bio agents. Actual biological agent studies will be important in this phase. PHASE III DUAL USE APPLICATIONS: Design and development of a fully portable LIBS analyzer system which is optimized for bio agent detection will have broad military and civilian applications for the medical, environmental, and food industries. Homeland defense and military applications include medical diagnostics of pathogens and disease as well as non-medical contamination avoidance sensors for biological warfare agents. KEYWORDS: Non-destructive, in-situ biological analysis, biological agent detection, detection A02-063 TITLE: Packaging for Radio Frequency Microelectronic (MEMS) Devices Subjected to Harsh Environments TECHNOLOGY AREAS: Electronics OBJECTIVE: Develop durable, low cost, Level 1 packaging for RF MEMS devices so that they can withstand extreme loading conditions and the harsh environment of the battlefield. To provide packaging for these devices that will render them more reliable by protecting its components from heat, dust, electromagnetic forces, shock waves, and G-forces. DESCRIPTION: RF Microelectronic systems are the backbone of many military systems, and their reliable function and mechanical integrity are paramount to mission success. These components are particularly susceptible to damage and failure due to their many connections, and their sensitivity to dust, moisture and electromagnetic forces. This is especially true under harsh loading and environmental conditions of the battlefield. For example, secondary shock waves from a nearby impact or explosion can compromise the hermetic seal, making the device susceptible to moisture and corrosion. Research in nanoscience has yielded new advances in multifunctional materials, and coatings that can provide protective packaging and/or stronger bonding between connections so that electronic components will be resistant to the effects of shock, corrosion, and temperature fluctuations. There is a need to design these components specifically for the extreme loading and environmental conditions required by military applications that include the coupled effects of electromagnetic forces, severe mechanical loading, and environmental conditions. PHASE I: Identify promising materials and technologies for the design RF MEMs packaging and connections such that they will withstand extreme conditions. Study the feasibility of these materials and technologies through the development of theoretical and computational models to predict the deformation, fracture and failure of the devices subjected to coupled loading conditions (thermo-mechanical-environmental). Investigate fabrication techniques to manufacture the packaging at low cost. Perform component level experiments to validate predictions. PHASE II: Develop prototype systems that can be used to demonstrate concepts and provide benchmark performance measures versus current technology. Accelerated aging tests should be performed to quantify their performance under thermal cycling and corrosion. In addition, testing should be performed to assess their performance under shock loading. PHASE III: Prototype designs from Phase II should be specialized for communications or radar applications and a plan for integrating these devices into the system should be developed. Performance, reliability, and durability under realistic environmental and dynamic loading conditions should be assessed to qualify the device along with design methodology and fabrication techniques so that a commercial product can be integrated into an actual military system. Develop methods for the scale-up manufacturing technologies needed for commercialization. Identify and develop new applications based on the results of Phases I and II. DUAL USE APPLICATIONS: There are a large number of dual use applications. Packaging of electronic components will be useful for a multitude of military and commercial applications. Military applications include communications, radar, missile guidance systems, tank navigation systems, and smart munitions. Non-military applications can extend to consumer electronics, cellular phones, auto, and other industries where electronics and harsh environments interact. REFERENCES: 1) Stuart B. Brown, William Van Arsdell, Christopher L. Muhlstein, Materials Reliability in MEMS Devices. 1997 International Conference on Solid-State Sensors and Actuators, Chicago, June 16-19, 1997. 2) S. L. Miller, M. S. Rodgers, G. LaVigne, J. J. Sniegowski, P. Clews, D. M. Tanner, and K. A. Peterson, "Failure Modes in Surface Micromachined MicroElectroMechanical Actuators", 1998 IEEE International Reliability Physics Symposium Proceedings, IRPS 1998, March 31-April 2, 1998, pp. 17-25. 3) "MEMS Reliability: The Challenge and the Promise", William M. Miller, Danelle M. Tanner, Samuel L. Miller, Kenneth A. Peterson, (Invited presentation and paper) 4th Annual "The Reliability Challenge," Dublin, Ireland, May 19, 1998, pp. 4.1-4.7. KEYWORDS : Sensors, Blast Resistance, Shock, Reliability, Environmental Aging A02-064 TITLE: Catalytic Oxidation of Hydrocarbons In Aqueous Solutions TECHNOLOGY AREAS: Chemical/Bio Defense OBJECTIVE: To develop a process for the catalyzed oxidation of hydrocarbons in water contaminated by washing military vehicles near the front lines. DESCRIPTION: One of the limiting factors in the forward deployment of military vehicles in a combat zone where there are potential poisonous agents is providing routine re-supply and maintenance. Once a vehicle has a surface contaminated with any of a series of invisible chemical agents (including engine oil, fuel, chemical warfare agents, and mud), biological agents, or radioactive materials, vehicle repair and refurbishment must be completed without incurring additional casualties. Even worse is the creation of an aura of fear on the part of maintenance personnel regarding their potential injury while simply touching a vehicle. Cleaning the contaminated vehicle surface by effective washing is an obvious solution to this potential of injury to maintenance personnel. The cost and amount of dedicated equipment used to bring fresh water to the front lines for vehicle washing is high. The responsible disposal of diluted chemically or biologically contaminated water created during the washing operation is also time and material intensive. The ability to remove the contaminants from the wash water, making it clean and sterile again, through the use of a simple on-site process which only requires a pump and small heater would greatly benefit the combat capability of the US Army. Supercritical Water Oxidation (SCWO) has long been groomed for the oxidation of hydrocarbons in aqueous solutions. However, the high temperature and pressure required to operate the process (1500 deg F and 3400 psig) create unacceptable corrosion conditions and solids precipitation problems that the SCWO units require robust designs using exotic alloys. Despite precautions, these extreme operating conditions cause premature equipment failure, complicated operating designs and expensive equipment. Corrosion and solids precipitation problems have prevented the extensive commercialization of the SCWO process. Chemical catalysis in the petro-chemical industry has a long, proven track record of achieving chemical oxidation of hydrocarbons at far lower temperatures. Lowering the temperature required for the oxidation reaction to take place would reduce corrosion and the problems associated with solids precipitation. Reducing the corrosion environment would manifest itself into lower equipment acquisition costs, extended operating life, more simple designs, less operating power and improve the reliability of such recycling equipment. PHASE I: Screen available catalysts formulations used in oxidation reactions using a typical wash stream such as is produced during the washing of combat vehicles. The wash stream would include engine oil and fuel components and mud as well as possible simultants for toxic warfare agents. Conversion rate, life expectancy and poisoning potential would be collected on candidate catalysts. A prototype system would be proposed from the results of Phase I. PHASE II: A prototype recycling vehicle washing system would be constructed and field evaluated. Process and equipment limits would be defined and a final revised design would be presented. Phase II would include the assesment of the systems ability to neutralize and remove biological agents and radioactive materials. PHASE III DUAL USE COMMERCIALIZATION: The conduct of military operations in a chemical environment requires safe field maintenance and access by military personnel in a timely and economical manner. Entire civilian businesses are being forced into using less effective washing technology due to environmental constraints in the disposal of the wastewater. A successful catalytic oxidation technology would allow the commercial washing industries to again use the more effective cleaning soaps with a simple water recycling process. This process would improve washing while protecting the environment using a simple, robust process for water recycling during military operations. REFERENCES: 1) Yu-Chu Yang, James A. Baker, and J. Richard Ward "Decontamination of Chemical Warfare Agents", Chem. Rev. 1992, 92, 1729-1743. 2) Yu-Chu Yang "Chemical Detoxification of Nerve Agent VX" Acc. Chem. Res. 1999, 32, 109-115. KEYWORDS: decontamination, washing, catalysis, oxidation Directory: osbp -> SBIR -> solicitations solicitations -> Army sbir 09. 1 Proposal submission instructions dod small Business Innovation (sbir) Program solicitations -> Navy sbir fy09. 1 Proposal submission instructions solicitations -> Army 16. 3 Small Business Innovation Research (sbir) Proposal Submission Instructions solicitations -> Air force 12. 1 Small Business Innovation Research (sbir) Proposal Submission Instructions solicitations -> Army 14. 1 Small Business Innovation Research (sbir) Proposal Submission Instructions solicitations -> Navy small business innovation research program submitting Proposals on Navy Topics solicitations -> Navy small business innovation research program solicitations -> Armament research, development and engineering center solicitations -> Army 17. 1 Small Business Innovation Research (sbir) Proposal Submission Instructions solicitations -> Navy 11. 3 Small Business Innovation Research (sbir) Proposal Submission Instructions Download 1.78 Mb. 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