Development of a Multi-analyte Biosensor Platform Based on Computationally-Designed Proteins

Antibody-based receptor scaffolds used in chemical and biological sensors suffer from certain inherent shortfalls. We propose an approach based on the use of computationally designed proteins as receptor scaffolds. Such receptor scaffolds overcome many of the problems encountered with antibodies. This approach offers the significant advantage of being a general method that provides a path to rapid development of specific receptors. We propose to transition fluorescent reagentless biosensor technologies from the academic laboratory in which they were originally developed into fieldable products. Specifically, we intend to develop biosensors that incorporate engineered periplasmic binding proteins (PBPs) that recognize and report organophosphate mimics and hydrolysis products of well-known nerve agents such as Soman (organophosphate surrogate is pinacolyl methylphosphonic acid, or PMPA) and Sarin (organophosphatesurrogate isopropyl methyl phosphonic acid, or IMPA). This work will initially proceed as a collaboration between Nomadics and the laboratory of Dr. H.W. Hellinga at Duke University Medical Center. Dr. Hellinga has developed PMPA-binding PBPs and is finishing development of IMPA-binding PBPs.