An integrated micro-sensing system for diagnostic testing of botulinum neurotoxins

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This proposal focuses on the development of 1) an integrated micro-sensing system capable of detecting in clinical samples (mouse sera) femtomolar (fM) concentrations of botulinum neurotoxin (BoNT), a bioagent of grave threat and utmost importance in homeland security and biodefense, and 2) a coherent interdisciplinary program integrating high quality teaching and outreach activities with research. The detection of BoNT utilizes an enzymatically cleavable membrane that is interfaced to a liquid crystal (LC), exploiting the intrinsic protease activity of BoNT and thereby leveraging the inherent amplification associated with assaying for an enzyme target. The cleavage of the membrane due to BoNT is amplified by the cooperative reorientation of the LC, which can in turn be measured via impedance sensing with the microsensor. The predicted sensitivity is fM concentrations of BoNT in ten microliter of a sample, corresponding to femtogram (fg) quantities of BoNT. The ultimate goal of this research is the creation of a low-cost, easy-to-use tool that allows rapid clinical diagnosis of botulism with high sensitivity and specificity. Intellectual Merit: This research will make significant contribution to the clinical diagnosis of botulism, a key issue in biodefense. The proposed microsystem can also be applied to many other toxins, thereby having broad range of applications related to biodenfense, environment monitoring, food safety and public health. In addition, this research will advance bioactive chemistries, hybrid microfabrication techniques, bioagent sensing, microfluidics, and fluidic/electronics integration schemes. Broader Impacts: The proposed project will generate significant educational opportunities for students at both college and K-12 levels in frontier research related to biodefense. The education and outreach components of this proposal include improving existing curriculum, developing new interdisciplinary courses, mentoring undergraduate and graduate students, especially underrepresented students, and dissemination and outreach to the local community and general public on science, engineering, and homeland security.