(Invited) Mining Microbes to Engineer Novel Biosensor Devices

We have developed a strategy for biosensor engineering that leverages an enormous and untapped reservoir for portable and inexpensive sensing parts: microbes. Microbes have evolved over 3 billion years to detect an array of stimuli relevant to biology, biotechnology, and our environment. They do so via proteins that have several desirable characteristics including: (1) they are already miniaturized and therefore portable, (2) they are inexpensive to generate with standard cloning techniques, (3) they can respond rapidly and with high sensitivity and specificity, and (5) they can be integrated into low cost electronic devices. Our strategy employs genomics and functional assays to screen microbial samples for sensor proteins specific for a target analyte, and to isolate the genes for these proteins. In addition to screening isolated single bacteria, our methods enable metagenomic screening of the full diversity of any microbiome, including unculturable and unidentified bacteria. Once harvested, proteins are optimized for their sensing characteristics using protein engineering, directed evolution, and computational modeling. We then develop these proteins into sensor devices using existing and novel transduction approaches. The talk will describe our screening approach and its application to the development of multiple sensors from two broad classes of microbial proteins: allosteric transcription factors and redox enzymes. The sensors discovered and developed through our approach can be readily deployed into a range of applications for portable, real-time, and inexpensive biosensing. The talk will preview our ongoing work to deploy our novel sensors into a wearable device for sweat and interstitial fluid monitoring. Figure 1