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DoD 2014.1 SBIR Solicitation

Agency: Department of Defense
Branch: Office for Chemical and Biological Defense
Program/Year: SBIR / 2014
Solicitation Number: 2014.1
Release Date: November 20, 2013
Open Date: December 20, 2013
Close Date: January 22, 2014
CBD14-101: Innovative concept for detection and identification of biological toxins
Description: OBJECTIVE: Design, develop and demonstrate concepts that will provide ability to detect and discriminate among various biological toxins that are identified threat agents. Particular emphasis is on disposable, low cost devices suited to in-field application. The solution should overcome limitations of present immunoassay-based detection schemes. DESCRIPTION: The concept is intended to provide means that help identify and further avoid individual"s exposure to select threat agents and identify contaminated materials. A specific interest is the identification of plant-derived toxins such as ricin. Ricin and related molecules are classic biological warfare agents as well as common threats delivered in rouge terror attacks via contaminated mail or other crude dissemination methods. The DoD, along with other government and civilian operations, require the ability to continuously monitor for general threats and then rapidly screen and identify threat and risk when a primary monitor is triggered. A cost-effective and reliable primary screen for biological toxin threats that can be used for field tests and may be integrated in fixed, continuous monitoring platforms is a highly desirable technology. Samples that trigger preliminary screen could then be passed to more precise and complex assessments to confirm and identify threat. The research is expected to develop materials which, will selectively interact and allow presumptive identification of biologically-derived toxins. Contemporary advances in biotechnology and materials science provide many approaches to integrate biological processes into sensor, forensic, and diagnostic processes. The proposed work should take advantage of current state-of-art methodologies to develop materials concepts that allow presumptive identification of threat agents and are versatile enough for application in hand-held portable test-kits as well as high-throughput, continuously operating monitors. The ideal design will be low cost and will readily integrate with commercial-off-the-shelf electronic equipment. The readout should be easy to interpret, and amenable to potentially monitor for numerous toxins simultaneously. The sensing modality will provide alternatives to existing antibody-based sensing and screening technologies. PHASE I: Combine innovative approaches for modification/functionalization of readily available materials for identification of plant-derived toxins. Incorporate material within assay to rigorously evaluate concept for proof-of-principle. Demonstrate proof of principle in a controlled laboratory environment. Demonstration will successfully detect and presumptively identify a single threat agent simulant and discriminate from a related molecule in laboratory sample. Detection sensitivity must be competitive with existing surface plasmon resonance-based technologies (threshold 200 ng/mL). PHASE II: Develop and demonstrate a hand-held prototype device that incorporates sensor recognition materials that can be tested in a relevant environment. The material may be further optimized to monitor or screen for multiple threats of concern simultaneously by incorporating multiplex concept. The concept prototype will maintain selectivity for defined toxins within complex environmental samples (e.g., surface waters, dust, household chemicals, foodstuff). The system should incorporate materials that simultaneously monitor for 3 or more threat agents and maintain sensitivity (threshold 200 ng/mL). PHASE III: The technology developed under this effort includes development for dual use applications in military and civilian areas related to operation, primary threat, and environmental monitoring.
CBD14-102: Deployable graphene-based chemical/biological sensors
Description: OBJECTIVE: Design and develop a deployable radio frequency (RF) based broadband impedance chemical/biological detection system suitable for field-deployable networks, UAV deployment applications, and stand-alone chemical/biological point detection. DESCRIPTION: Chemical-warfare (CW) agents, Biological Warfare (BW) agents, explosive materials, and toxic industrial chemicals/materials (TIC/TIM) are compounds that can be used as weapons of mass destructions. A priority of the DoD Joint Chemical and Biological Defense Program is development of new and improved chemical and biological sensors. To achieve this objective, innovative materials and designs will be required. Low-cost, radio frequency (RF) wireless chemical sensors and biosensors are expected to have significant applications in defense and homeland security and are ideal for deployment on micro-unmanned aerial vehicles and used in field-deployable networks, and for stand-alone point detection. The outstanding carrier mobility, the excessive large surface area per unit mass and the adjustable surface chemistry make graphene an excellent candidate for chemical/biological sensing. Most of the graphene-based chem/bio-sensing approaches, however, rely on registering the variation of either the DC resistance or the electrochemical surface potential. The major restrictions are chem/bio molecules usually experience transformation (e.g. polarization due to the applied high voltage) at DC or low frequency, and high background noises. In addition, the current techniques confront a number of challenges in recognition, selectivity, spatial resolution and quantification. At radio frequencies, the motion of chem/bio molecules and water masking effects can be largely suppressed, thus reducing background noise and increasing sensitivity. Moreover, interfacial capacitance between the target molecule and graphene surface only becomes pronounced and detectable at RF, providing additional information for detection. This topic seeks new and innovative approaches to design and develop a deployable radio frequency (RF)-based broadband impedance chemical/biological detection system. Due to time/investment constraints in the Phase I/Phase II SBIR project period-of-performance, the offeror should focus on proof-of-concept using chemical agent simulants with an approach that permits future expansion of the active sensing technology to encompass biological agents in later phases. Such a system is expected to outperform conventional sensors in sensitivity, reliability, selectivity (false-positive/false-negative rates), and high-throughput analysis (rapid response time). Some nerve agents have time-weighted average exposure limits at sub-ppb concentration; thereby, the proposal should target sensing CWAs with sensitivity to sub-ppb (by using CWA simulants in the demonstration.) Methods that only address the chemical/biological agents sensing capability such as conventional monitoring variation of resistance and electrochemical potential are not sufficient to meet the intent of this topic, but could be employed to achieve the end objective. Functionalization of graphene with recognition molecules to achieve selective detection of chemical or biological threat agents is highly desired. RF transmitter and rectenna are needed to be implemented in the system to transmit detected information wirelessly. The system must be easy to use, demonstrate real-time sensing with sub-ppb detection sensitivity capable of selective detection (by using a combination of CWA simulants and interferences, e.g., water vapor) and capable of in-situ multiplexed chemical/biological sensing with no need for sample preparation. The system must also be capable of self-recovery, allow prolonged integration time and continuous monitoring of threat changes in the environment, and be used outdoors. The prototype system is anticipated to be readily remote controlled with a high detection probability (PD) and low false alarm (FA) rate: PD>95% and FA<5%, and be able to identify chemical or biological threat agents. PHASE I: Design graphene-based chemical/biological sensors meeting goals identified above and validate through modeling and simulation. Fabricate proof-of-concept prototype that will demonstrate the sub-ppb sensitivity and sensing selectivity of chemical agent simulants, and be capable of in-situ multiplexed chemical/biological sensing. PHASE II: Fully develop, fabricate, and demonstrate a working impedance chemical/biological graphene-based detection system. Expectations for this phase would include a fully integrated version of the proposed solution that could be evaluated in a relevant environment. PHASE III DUAL USE COMMERCIALIZATION: Military Application: Military applications include deployment on micro-unmanned aerial vehicles, use in field-deployable detection networks, and use as a stand-alone point detection technique. Commercial Application: Highly sensitive and selective sensors could find application in the healthcare industry for early disease detection and construction of a comprehensive quantitative and personalized profile for more accurate diagnosis and better disease management.
CBD14-103: Micro-electric Technology for Respiratory Protection Systems
Description: OBJECTIVE: Design and develop micro-electric devices suitable for integration into a face or helmet mounted respiratory protective system. DESCRIPTION: Military respirators used for protection against chemical, biological, radiological, nuclear (CBRN) threat agents currently have no means to reduce heat and moisture burden associated with prolonged respirator wear. Traditional powered air-purifying blower systems used to supply clean breathing air can offer significant evaporative cooling and other benefits, such as lens defogging, but are not suitable for integration due to their excessive weight, bulk, and power requirements. Similarly, state-of-the-art technologies for vapor-compression heat pumps and thermoelectric devices are too large, heavy and/or power-hungry for practical application; and passive technology for heat and moisture adsorption such as phase change materials, wicking materials, and heat pipes has proven ineffective. Innovative micro-electric systems with sensor feedback technologies are sought to improve comfort and performance of military respirators while minimizing size, weight and power demand in order to make them practical for military use. Specific example applications include but are not limited to: (1) anti-fog management that provides rapid clearing of eye lenses including high work rates in basic cold conditions (see MIL-STD-810G, 31 Oct 2008); (2) air-management solutions including on-demand miniature blowers and humidity control devices that can generate sufficient airflow (e.g. 20 to 30 Liters/min, minimum) and low-power requirements (e.g. less than 5 watts); (3) breathing-air management systems to maintain proper air quality (i.e. proper oxygen and carbon dioxide levels) and extend mission range/time of respirators for high-hazard environments that include Self-Contained Breathing Apparatuses (SCBA) and Closed-Circuit (CC) SCBA configurations; (4) breathing and thermal management systems responsive to physiological monitoring. The devices must be intrinsically safe, hygienic, durable, and easy to clean. The devices should be able to be integrated with the existing military or applicable commercial respirators, should be lightweight (less than 50 grams), and should not degrade or otherwise adversely impact the vision or the flexibility and sealing quality (e.g., fit or protection factor performance) of the mask. The devices and components, including their housings, must be rugged and able to withstand a wide range of temperature and environmental extremes. PHASE I: Develop an innovative micro-electric system and demonstrate the feasibility of designing and fabricating a"bread-board"system. Demonstrate robustness of the control system to sense the targeted environmental and/or physiological states and maintain the desired performance over the targeted range of operational conditions. Demonstrate that the device can be miniaturized and meet power demand objectives. Produce an objective prototype design and estimate, size, weight, power demand, cost, and net benefit of the production item. PHASE II: Refine and optimize Phase I bread-board micro-electric system. Characterize prototype performance using a suitable respirator system as a test bed. Optimize test bed performance and demonstrate the micro-electric system(s) by assessing and validating performance under an operational relevant range of external environmental (temperature/humidity) conditions, in-mask heat/humidity loads, and operationally relevant breathing rates. Develop and demonstrate that the devices including sensors, processing, power and communications can be miniaturized where total weight of the entire system to include housing and electronics should not exceed 50 grams. Demonstrate the technology can quickly identify repeated changes in conditions occurring in the same region. Develop ability to store baseline conditions acquired during wear and that data can be communicated for external monitoring and analysis. Develop and demonstrate technology to warn user of changing conditions and/or differences from the baseline. Provide pre-production prototypes of respirators with embedded micro-electric technology. Demonstrate the feasibility of these sensors to be miniaturized and to operate in temperature and moisture extremes. PHASE III: Fully integrate solution into a military CBRN-protective respirator system. Optimize fabrication process to demonstrate large-scale production capabilities and to demonstrate ability of technology to be incorporated into multiple mask systems. Demonstrate the ability to commercialize the technology and establish partners to expand commercialization. PHASE III DUAL USE APPLICATIONS: Potential alternative applications include industrial, international, and commercial respiratory protection systems (e.g., firefighting helmets, HAZMAT response ensembles, etc.).
CBD14-104: DNA Origami-based Bio-scavengers for Nerve Agent Sequestration
Description: OBJECTIVE: Design and develop DNA origami-based bio-scavengers with high affinity for organophosphorus compounds and demonstrate these systems can be optimized for use in the molecular sequestration of nerve agents. DESCRIPTION: The DOD has the need for a universal organophosphorus (OP) scavenger that will protect against multiple OP compounds, including all existing nerve agents. The ideal scavenger should be rapid, irreversible, and specific and have a prolonged circulation time in the bloodstream. The ideal scavenger should also be biologically innocuous in the absence of OP compounds. In particular the optimum scavenger should not stimulate an immune response. Scavengers can also be used prophylactically by inactivating OP compounds before they can react with the target acetcylcholinesterase (AChE). In biological systems, avidity is often used to describe the combined strength of multiple bond interactions. Avidity is distinct from affinity, which is a term used to describe the strength of a single bond. Avidity is the combined synergistic strength of bond affinities rather than the sum of bonds. Avidity is commonly applied to antibody interactions in which multiple binding sites simultaneously interact with a target molecule. When many binding interactions are present at the same time, transient unbinding of a single site does not allow the molecule to diffuse away, and binding of that site is likely to be reinstated. It has been demonstrated multiple binding sites can increase the effective binding of a molecular species by up to five orders of magnitude relative to the affinity of any univalent bond within the system. A DNA origami structure may have up to 250 binding sites on a single moiety. This presents a powerful platform for molecular sequestration. Current treatment of OP poisoning involves a combination of therapies. Drugs such as atropine are administered to counteract the effects of acetylcholine. An oxime such as pralidoxime reacts with the inhibited cholinesterase, removing the organophosphate from cholinesterase. The cholinesterase is then able to resume normal function. Anticonvulsant drugs such as diazepam are used to control tremors and convulsions. These therapies are effective in preventing death. However, performance deficits, behavioral incapacitation, loss of consciousness, and potential permanent brain damage can occur in the absence of further treatment. An effective bioscavenger that can reduce the concentration of all OP"s to low levels (less than one micromolar) in a short period of time (less than 2 minutes) would provide DOD personnel with needed protection from the harmful defects of nerve agent exposure. Intravenous (IV) plasma derived butyrylcholinesterase (hBuChE) is a very effective bioscavenger that has been shown to provide protection from lethal exposure to nerve agent using animal models. However, hBuChE is logistically difficult to use in battle field scenarios since it typically requires refrigeration. Attempts have been made to lyophilize hBuChE. However, reconstituted hBuChE shows a considerable loss in activity. Furthermore, hBuChE is perishable, and a constant supply can only be maintained with on-going blood donations. Butryrlcholinesterase can also be produced using recombinant methods (rBuChE). However, rBuChE has been shown to be less effective than hBuChE. In general protein folding is unpredictable and difficult to control. Lyophilization and reconstitution can produce unpredictable results. Proteins are perishable and tend to be very immunogenic. Hence, a non-protein-based bio-scavenger may provide significant advantages for treating nerve agent exposure. Recent advances in DNA-based origami and hybrid DNA-based nanostructures that combine origami construction with designer motifs offer a new bio-technological pathway to man-engineered bio-scavengers. DNA origami is the folding of DNA strands into 2D or 3D, and DNA motifs may be utilized to array individual DNA origami units into even larger and more complex bio-nanostructures. In a DNA origami, a long single-stranded plasmid DNA, like M13mp18 ssDNA, can be folded into a space-filling curve and held in place with shorter"staple"strands, which crosslink and stabilize the structure, enabling the formation of complex 2D and 3D shapes. The molecular weight of a typical DNA origami structure (e.g., based on M13mp18) can be over 2M daltons with a relatively large surface area, which can be decorated with multiple precisely addressed molecular recognition units. Theoretically, each staple strand can attach to one molecular recognition unit, which will allow for the capture of up to 250 target molecules by each individual DNA origami construct, and this number can be multiplied using DNA motif-based arraying techniques. Therefore, DNA origami-based platforms can present large numbers of molecular sequestration sites. Furthermore, such DNA-based bio-scavengers would not elicit a strong immunogenic response. This is in contrast to proteins where strong immunogenic responses are normal. A strong immunogenic response to a scavenger can have very negative implications. For example, a person can become allergic to cholinesterase-like molecules that can lead to autoimmune-like symptoms. In general, the design of large and diverse DNA-based nanostructures using naturally occurring genetic components (i.e., using only four base pairs) involves a great deal of computational complexity. Indeed, the task of determining the DNA sequence sets required for the self-assembly of highly optimized and stable geometrical forms presently requires the use of specialized algorithms and distributed computing. While active DOD programs are presently advancing the state of the art in design automation software for DNA architectures, the design and associated synthesis problem can be greatly simplified through the use of expanded DNA alphabets such as AEGIS (Artificially Expanded Genetic Information System) that uses twelve nucleic acids in its genetic code. These artificially expanded DNA systems offer many strategic advantages (e.g., managing non-canonical forms, more chemically stable, etc.) and can be used to realize fundamental building blocks that allow for the additional of clickable functionality (i.e., which could be useful for defining electro-optical diagnostic techniques for monitoring molecular sequestration action). The chances of an adverse immune reaction would also be further reduced through the use of AEGIS type components since the artificial bases do not exist in nature; it is unlikely that a person will have future encounters with the artificial structure produces by these bases. Hence, DNA origami-based platforms that utilize hybrid building blocks represent a promising pathway to a novel class of bio-scavengers for nerve agent sequestration. PHASE I: Formulate a complete design for a bio-scavenger based upon DNA origami components that sequesters organophosphorous compounds from blood using integrated molecular capture. It is also strongly recommended that the DNA origami-based platform be specified so as to incorporate electro-optical based diagnostic monitoring of the sequestration process. The scavenger should reduce OP"s concentrations to low levels (less than one micromolar) in a short period of time (less than 2 minutes). The scavenger should remain in the bloodstream for an extended period of time (at least 10 days) after administration at levels that provide protection from OP"s. The scavenger should be non-immunogenic. The scavenger should be lyophilizable and remain active after reconstitution. The lyophilized form of the scavenger should be stable for extended periods of time (at least 2 years at temperatures not exceeding 50 degrees C). Demonstrate proof of concept and feasibility using candidate OP binding moiety testing. For demonstration purposed, is can be assumed that the initial OP concentration can be as high as one millimolar. An in vitro study of a pesticide or other nerve agent simulant can be used for proof-of-principle in Phase I. PHASE II: Develop and test a DNA origami-based bio-scavenger that achieves the functionality and performance requirements specified in the Phase I requirements. It is expected that the bio-scavenger will first be tested using OP pesticides and/or nerve agent simulants. The bio-scavenger should also be tested against bona fide OP nerve agents. Since testing with OP nerve agents is required during Phase II development, and as small business firms are unable to handle and utilize chemical weapon agents (CWAs), a testing facility approved to utilize these materials must be identified (it strongly recommended that a qualified DOD laboratory or appropriately licensed commercial laboratory be identified for use in testing against the OP nerve agents). PHASE III: Research and development during Phase III efforts will be directed toward refining final deployable designs for OP scavengers. In vivo safety and efficacy testing in animal models will be performed. Design modifications based on results from tests conducted during Phase II will be incorporated. Manufacturability specific to the Joint Chemical and Biological Defense Program CONOPS and end-user requirements should be examined. Molecular scavengers will have numerous commercial applications, particularly in the field of medicine.
CBD14-105: High-affinity monoclonal antibodies that target Burkholderia Polysaccharide
Description: OBJECTIVE: This topic solicits the development of serotype-specific, high-affinity monoclonal antibodies that target Burkholderia mallei and Burkholderia pseudomallei and/or O-polysaccharide and capsular polysaccharide. DESCRIPTION: Burkholderia mallei, causative agent of glanders, and Burkholderia pseudomallei, causative agent of melioidosis, are recognized as potential biological warfare threat agents. During World War I, glanders was believed to have been spread deliberately by German agents to infect large numbers of Russian horses and mules on the Eastern Front, which resulted in humans acquiring the infection. In addition, the Japanese deliberately infected horses, civilians, and prisoners of war with glanders at the Pinfang (China) Institute during World War II. The Soviet Union is also believed to have weaponized Burkholderia as a potential biological warfare (BW) agent after World War II. Currently, there are no licensed prophylactic countermeasures to prevent infections caused by these intracellular pathogens. Limited efforts to develop B. mallei and B. pseudomallei vaccines comprised of O-polysaccharide- (OPS) and capsular polysaccharide (CPS) have had limited success. However, given the importance of these targets in protective immunity, identification of alternative strategies to develop prophylactic countermeasures against Burkholderia is warranted. In particular, the development of methods to isolate high-affinity OPS- and CPS-specific monoclonal antibodies is anticipated to result in the development of a prophylactic countermeasure against these weaponizable agents. PHASE I: It is anticipated that studies in this initial phase will focus on the development of a reagents and an animal model system that will enable the production of B. mallei and/or B. pseudomallei OPS- and CPS-specific antibody responses. Use of attenuated or non-pathogenic strains of Burkholderia during this phase is recommended, so long as the selected strains expression antigenically-identical OPS and CPS to those expressed by wild-type B. mallei and B. pseudomallei. It is important that offerors ensure strain-specific antigenic epitopes in the B. mallei and B. pseudomallei OPS- and CPS are maintained. PHASE II: It is anticipated that this phase will focus on isolation of OPS- and CPS-specific hybridoma clones and demonstration of specificity using in vitro immunochemistry methods. Studies to enhance affinity OPS- and CPS-specific monoclonal antibodies are also within the scope of this phase. It is also envisaged that if an acceptable animal model is available, an initial challenge study will be conducted as part of a down-select process to identify antibodies with the highest affinity, specificity and potency. All animal studies will be conducted under the appropriate containment and review, and at an accredited location. PHASE III: Studies in this phase may focus on monoclonal antibody humanization and manufacturing process development. This phase is also expected to include a demonstration that the humanized monoclonal antibodies maintained specificity and affinity for the respective OPS and CPS targets. After successful completion of the aforementioned milestone and if the monoclonal antibodies merit further development, cGMP manufacturing will be conducted. Material produced during cGMP manufacturing will be used to assess toxicity and potency in an appropriate animal model. Proof-of-concept efficacy studies in non-human primates (NHPs), if an acceptable model is available, are also within the scope of this phase. Challenge studies will be conducted under appropriate biosafety containment conditions. Milestones: Each phase of the project will be milestone driven. The Principal Investigator will propose milestones prior to starting any phase of the project. Deliverables: Major milestone schedule and decision tree for project Monthly reports in the format of a slide deck and teleconference Quarterly written reports (in addition to slide deck and teleconference) Final report including major accomplishments and proposed path forward PHASE III DUAL USE APPLICATIONS: Successful development of effective B. mallei and B. pseudomallei monoclonal antibodies will provide important countermeasures for the warfighter and have broader commercial potential as a public health tool in diagnostics and prophylaxis in endemic regions to control the spread of this emerging pathogen.