SENSORS: Nanoparticles-based Biosensor for Direct Detection of Organophosphate Chemical Warfare Agents and Neurotoxic Pesticides

Project Information

Principal Investigator	Aleksandr Simonian
Institution	Auburn University
Project URL	View
Relevance to Implications	Marginal
Class of Nanomaterial	Engineered Nanomaterials
Impact Sector	Human Health
Broad Research Categories	Characterization
NNI identifier

Funding Information

Country	USA
Anticipated Total Funding	$678,563.00
Annual Funding	$169,640.75
Funding Source	NSF
Funding Mechanism	Extramural
Funding Sector	Government
Start Year	2003
Anticipated End Year	2007

Abstract/Summary

There is a broad spectrum of neurotoxic organophosphates (OP) that are subject to widespread distribution in the environment for insect and biopathogen control. In addition, there have been bioterrorism threats and actual attacks involving the chemical warfare agents Sarin and VX (also neurotoxic OPs). The potential threats of these neuroxins as weapons of mass destruction necessitate the development of robust and sensitive methods for OP detection that can discriminate between common garden pesticides that pose little threat to society under normal usage and the weapons of mass destruction that could decimate military and civilian targets. This project explores enzyme-based biosensors, which are linked to gold nanoparticle scaffolds, that permit the direct detection of ultra low concentrations (10-10 M) of OP neurotoxins in multi-component environments such as ground water, waste water, food, and soil. The primary biosensor element consists of a metal nanosurface, one or more broad-spectrum organophosphate hydrolase-enzyme biorecognition elements, fluorescent decoys that compete specifically for binding with neurotoxins of interest, and an optical system for fluorescence detection. The nanoparticle-molecular interface is designed to alter the optical properties of the fluorescent decoy when bound by the biorecognition element, giving rise to a unique signal that changes when it is released. The development of this technology into a family of robust, sensitive, and discriminating chemical sensors capable of identifying and quantifying organophosphorus (OP) nerve agents and pesticides involves: (i) the development of appropriate decoys that can compete specifically with different agents, (ii) the selection or modification of enzymes via rational, site-directed mutagenesis to finely tune catalytic enzyme properties (both affinity and substrate specificities); (iii) the development of the optimum sensor platform, both in terms of nanoparticle properties and attachment chemistries and optical systems for light collection; and (iv) the design of detection algorithms for robust sensor performance. Intended applications of the proposed biosensor include the monitoring of soil, air, and/or water quality, which will allow prompt, accurate reporting on environmental contamination, thus initiating the appropriate response to toxic agents in deployment of detoxification procedures and remediation of contaminated sites. Many organophosphates, either in the form of pesticides (phosphotriesters and phosphonthioates) or chemical warfare (CW) agents (phosphonofluoridates and phosphono-thioates), are known to be neurotoxic as inhibitors of acetyl-choline and butryl-choline esterases. Existing methods for organophosphate detection are poorly discriminating and technologically complex. Such capabilities are poorly suited to field conditions and are not functionally available to first responders, military operations, nor small companies, farmers, and communities. Thus, robust, easy to use, sensitive, and selective organophosphate sensors, such as those developed in this project are needed, both to protect public health and to ensure homeland security. This inherently interdisciplinary project provides an excellent opportunity for training of graduate and undergraduate students in technologies appropriate for ensuring homeland security. This project also constitutes an easily understood example for high school and middle school science classes of the application of biotechnology and technology to solve important societal problems.

There is a broad spectrum of neurotoxic organophosphates (OP) that are subject to widespread distribution in the environment for insect and biopathogen control. In addition, there have been bioterrorism threats and actual attacks involving the chemical warfare agents Sarin and VX (also neurotoxic OPs). The potential threats of these neuroxins as weapons of mass destruction necessitate the development of robust and sensitive methods for OP detection that can discriminate between common garden pesticides that pose little threat to society under normal usage and the weapons of mass destruction that could decimate military and civilian targets. This project explores enzyme-based biosensors, which are linked to gold nanoparticle scaffolds, that permit the direct detection of ultra low concentrations (10-10 M) of OP neurotoxins in multi-component environments such as ground water, waste water, food, and soil. The primary biosensor element consists of a metal nanosurface, one or more broad-spectrum organophosphate hydrolase-enzyme biorecognition elements, fluorescent decoys that compete specifically for binding with neurotoxins of interest, and an optical system for fluorescence detection. The nanoparticle-molecular interface is designed to alter the optical properties of the fluorescent decoy when bound by the biorecognition element, giving rise to a unique signal that changes when it is released. The development of this technology into a family of robust, sensitive, and discriminating chemical sensors capable of identifying and quantifying organophosphorus (OP) nerve agents and pesticides involves: (i) the development of appropriate decoys that can compete specifically with different agents, (ii) the selection or modification of enzymes via rational, site-directed mutagenesis to finely tune catalytic enzyme properties (both affinity and substrate specificities); (iii) the development of the optimum sensor platform, both in terms of nanoparticle properties and attachment chemistries and optical systems for light collection; and (iv) the design of detection algorithms for robust sensor performance. Intended applications of the proposed biosensor include the monitoring of soil, air, and/or water quality, which will allow prompt, accurate reporting on environmental contamination, thus initiating the appropriate response to toxic agents in deployment of detoxification procedures and remediation of contaminated sites.

Many organophosphates, either in the form of pesticides (phosphotriesters and phosphonthioates) or chemical warfare (CW) agents (phosphonofluoridates and phosphono-thioates), are known to be neurotoxic as inhibitors of acetyl-choline and butryl-choline esterases. Existing methods for organophosphate detection are poorly discriminating and technologically complex. Such capabilities are poorly suited to field conditions and are not functionally available to first responders, military operations, nor small companies, farmers, and communities. Thus, robust, easy to use, sensitive, and selective organophosphate sensors, such as those developed in this project are needed, both to protect public health and to ensure homeland security. This inherently interdisciplinary project provides an excellent opportunity for training of graduate and undergraduate students in technologies appropriate for ensuring homeland security. This project also constitutes an easily understood example for high school and middle school science classes of the application of biotechnology and technology to solve important societal problems.