This SBIR project is in response to the call for the development of rapid and portable diagnostic tools for chemical threat exposure, suitable for use by emergency care providers in order to guide medical countermeasures. The broad objective of this proposal is to develop an extremely sensitive and selective biosensor device capable of detecting and discriminating proteins in human serum samples taken from personnel that have been exposed to potentially harmful levels of organophosphate-based nerve gas. This represents a novel approach in biomarker analysis because exposure to each different organophosphate (OP) chemical nerve agent results in a distinct protein """"""""fingerprint"""""""" structure that can be identified, distinguished from other agents, and quantified. Using novel sensor thin polymer film technology, reporter domains will be customized with specific protein-recognition molecules that detect the OP poisoned proteins. This will make it possible to develop an inexpensive, yet highly rapid, and accurate device to analyze exposure to OP chemical agents, assess the type and extent of OP agent exposure and then this information will be used to guide the therapeutic intervention necessary. The major milestones in this program are first to show proof-of-principal for the sensitivity and reliability of the film sensor element, second to demonstrate reproducible and accurate detection of OP-modified proteins in actual serum samples, and third, construct a prototype breadboard device that will guide the design of the commercial biosensor device. To accomplish these milestones, a collaboration has been established with a group specializing in OP toxified proteins. These scientists will provide the biorecognition molecules for film conjugation. Researchers familiar with bioconjugation and film preparation will construct the sensor elements. Samples of human serum containing toxified proteins will be then used to measure the film response. Finally, optical and electrical engineers will be utilized to assist in designing and assembling the prototype demonstration device. The end user of such a device is anticipated to be the field personnel and mobile medical units likely to encounter situations where combat troops have been exposed to OP chemical agents as well as civilians placed under terrorist threat. Potential public exposure to two classes of related organophosphate (OP) chemical agents are pesticides and nerve gases. Through either accidental over-exposure to pesticides or acts of bioterrorism, these agents can fatally harm humans. Realization of the proposed biosensor device will allow, as never before, rapid assessment of type and degree of OP exposure, and direct medical personnel to appropriate treatment modalities. ? ? ?

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Small Business Innovation Research (SBIR) Cooperative Agreements - Phase II (U44)
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Special Emphasis Panel (ZRG1-DIG-A (57))
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Pancrazio, Joseph J
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Ateris Technologies, LLC
United States
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Hitt, David M; Belabassi, Yamina; Suhy, Joyce et al. (2014) Chemoenzymatic resolution of rac-malathion. Tetrahedron Asymmetry 25:529-533
Belabassi, Yamina; Chao, Chih-Kai; Holly, Ryan et al. (2014) Preparation and characterization of diethoxy- and monoethoxy phosphylated ('aged') serine haptens and use in the production of monoclonal antibodies. Chem Biol Interact 223:134-40
Kaleem Ahmed, S; Belabassi, Yamina; Sankaranarayanan, Lakshmi et al. (2013) Synthesis and anti-acetylcholinesterase properties of novel ?- and ?-substituted alkoxy organophosphonates. Bioorg Med Chem Lett 23:2048-51
Ahmed, S Kaleem; Etoga, Jean-Louis G; Patel, Sarjubhai A et al. (2011) Use of the hydantoin isostere to produce inhibitors showing selectivity toward the vesicular glutamate transporter versus the obligate exchange transporter system x(c)(-). Bioorg Med Chem Lett 21:4358-62
Etoga, Jean-Louis G; Ahmed, S Kaleem; Patel, Sarjubhai et al. (2010) Conformationally-restricted amino acid analogues bearing a distal sulfonic acid show selective inhibition of system x(c)(-) over the vesicular glutamate transporter. Bioorg Med Chem Lett 20:2680-3
Bharate, Sandip B; Prins, John M; George, Kathleen M et al. (2010) Thionate versus Oxon: comparison of stability, uptake, and cell toxicity of ((14)CH(3)O)(2)-labeled methyl parathion and methyl paraoxon with SH-SY5Y cells. J Agric Food Chem 58:8460-6
Prins, John M; George, Kathleen M; Thompson, Charles M (2010) Paraoxon-induced protein expression changes to SH-SY5Y cells. Chem Res Toxicol 23:1656-62
Bharate, Sandip B; Thompson, Charles M (2010) Antimicrobial, antimalarial, and antileishmanial activities of mono- and bis-quaternary pyridinium compounds. Chem Biol Drug Des 76:546-51
Guo, Lilu; Suarez, Alirica I; Braden, Michael R et al. (2010) Inhibition of acetylcholinesterase by chromophore-linked fluorophosphonates. Bioorg Med Chem Lett 20:1194-7
Bharate, Sandip B; Guo, Lilu; Reeves, Tony E et al. (2010) Bisquaternary pyridinium oximes: Comparison of in vitro reactivation potency of compounds bearing aliphatic linkers and heteroaromatic linkers for paraoxon-inhibited electric eel and recombinant human acetylcholinesterase. Bioorg Med Chem 18:787-94

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