SBIR-STTR Award

The extreme toxicity of organophosphate (OP) chemical warfare agents (CWA) is due to their specific, rapid, and irreversible reaction with cholinesterase enzymes. A significant portion of this reactive nature of OP agents is directly due to the unique metabolically active environment found in and around cells. The goal of this proposal is to harness this unique intracellular environment to create a new class of highly sensitive, robust, and field portable sensor for rapidly detecting military personnel exposure to OP CWAs. In its final configuration, the proposed nanoparticles could be delivered as intradermal tattoos, allowing for rapid and personalized detection of potentially toxic OP agents. In Phase I, Agave BioSystems, in collaboration with Dr. Carl Batt of Cornell University, proposes to develop a warfare agent (CWA) detection system by incorporating fluorescent dyes demonstrated to sense CWAs into biocompatible nanoparticles that will serve as the support for the dye and the site of the response. The ability of these dye-impregnated nanoparticles to detect the presence of organophosphate CWAs will be tested in human cells. The goal is to create a system that utilizes human cellular chemistry to aid in the detection of potential CWA exposure.

Benefit:
In addition to detecting organophosphates, these types of nanoparticle sensors will have applications beyond CWAs since the nanoparticles are capable of supporting dyes capable of sensing myriad of other toxicants biomolecules. The potential diagnostic markets for this approach extend to VOC and other toxic industrial chemical detection in homeland security, law enforcement and industrial hygiene settings. The nanoparticles-based sensors could also be adapted for the detection of lactate, glucose, hydration, and corticosteroids levels.

Keywords:
Organophosphate, chemical warfare agents, nanoparticles, intradermal, fluorescent, intracellular, tattoo

Protection of first responders who are exposed to hazards including chemical warfare agents (CWAs) is a very critical need. The need is derived from not only their welfare but their ability to respond, protect the community and provide logistical support to the response. A simple exposure monitor would provide critical information to the first responder and allow them to respond accordingly and to also help to monitor the environment. Exposure monitoring would also provide a more realistic picture of the threat with multiple points of sampling. Therefore, it would be useful to develop systems that could harness the body’s own chemistry to help detect the presence of CWA exposure in the field. CWAs are toxic because of their direct and indirect impact on biological processes in the human body. Agave BioSystems, in collaboration with Dr. Carl Batt of Cornell University are exploring nanoscale materials specifically tailored to create a new class of highly sensitive, robust and personal platform to determine military personnel exposure to OP CWAs. Agave BioSystems has demonstrated that the dye impregnated NPs are responsive to CWA simulants in a cellular environment. During the Phase II program, improved dye impregnated NPs and a prototype NP detector will be developed. The fluorogenic NPs will be incorporated into tattoos to create an in vivo biosensor capable of rapid detection of OP CWA exposure.

Benefit:
The possibility of CWA troop exposure to CWA agents is of major concern to the US military. A variety of systems exist to detect the presence of CWA agents in non-biological settings, but the exposure of humans to these agents can often go undetected until symptoms begin to appear. The development of a simple, biologically based system for detecting either acute or chronic CWA exposure would be of significant benefit to deployed military troops. In this STTR Phase II program, Agave BioSystems, in collaboration with Dr. Carl Batt of Cornell University, propose to develop a fluorogenic nanoparticle sensor that can be imbedded into the dermal layer of military personnel as a tattoo. This tattoo would have the unique characteristic of becoming fluorescent upon exposure to low levels of organophosphate CWAs. A small, hand-held optical sensor would then be used to record changes in fluorescence emitted from the tattoo, rapidly indicating exposure to potential CWAs. In addition to military personnel, civilian first responders are also at risk of exposure to organophosphate agents, either as CWAs dispersed by terrorists or as insecticides present in high concentrations at agricultural and industrial sites. First responders can include police, fire, and EMS personnel, as well as search and rescue, and National Guard troop. While the exact number of first responders in the US is not known, some estimate that there may be as many 10 million people who could be characterized as first responders. According to the Bureau of Labor Statistics, there were over 1.3 million professional and volunteer fire personnel, about 800,000 police, and about 250,000 EMTs and paramedics in the US alone. While it may not be necessary to use an implantable tattoo biosensor for detecting OP exposure in every first responder, the market for tattoos and fluorescence monitors for US military and National Guard troops, as well as police, fire and EMS personnel could be well over 1 million individuals. If even a small fraction (1%) of this number requires monitoring, the market for fluorescent biosensor tattoos and handheld monitors could exceed $10 million. In addition to the detection of OP CWAs and pesticides, implantable biosensors such as those described in this proposal, adaptation of this technology could readily yield biosensors capable of detecting a wide range of chemical contaminants, such as volatile organic compounds (VOCs) and toxic industrial chemicals (TICs). Potential diagnostic markets for VOC and related compound detection include homeland security, law enforcement and the military. The chemical modularity of the approach described herein should ably address the need for real time, field deployable sensors potentially capable of detecting myriad families of chemical toxicants in a multitude of settings. Upon completion of the Phase II program, Agave BioSystems will develop a detailed Phase III plan for the commercialization of the resulting technology.

Keywords:
Organophosphate, nanoparticles, fluorogenic, hand-held prototype, tattoos, CWA detection