Bio-Based "Molectronic" Devices for Bidirectional Molecular-to-Electronic Signal Transduction

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Recent revelations have linked the human microbiome of the gastrointestinal tract to disease, behavior, and even mental health. Yet, there are few methodologies that enable study of these linkages, particularly the molecular signaling processes between the molecules, cells, and tissues involved, let alone their connection to behavior. Human and animal studies are expensive and time consuming, and they typically do not provide information at the molecular level. Importantly, it is at this level that information is needed. Culturing human cells and tissues on miniature microfluidic devices to mimic actual systems in the human body has been considered as one of the most promising alternatives to human or animal studies. While potentially transformative, these devices can be complex, as they sometimes include nutrient supplies, cells, actuators, pumps, valves, and even detector systems. To simplify, the principal investigator (PI) proposes a modular approach comprised of optimally designed subsystems. Their approach will also provide new efficient avenues for manipulating these cells and understanding their responses to molecular signals. Microelectrodes will be integrated and directly connected to cells and tissues for stimulating and interrogating cellular responses. Because the biological systems are "wired" to electrodes, this enables "programmed" function and highly accurate assessment of responses.Previously the PI's group has developed methods to electronically actuate and record signaling processes among bacteria and epithelial cells of human GI tract. While information processing in biology is accomplished by the secretion and perception of molecules, information processing within electronic devices is accomplished using electrons. The methodologies they have developed interconvert information content as it flows from molecules to electrons and back. To do this, they use synthetic biology and thin film microfabrication methodologies to assemble "smart" interfaces between biological systems and microelectronic devices. They base their methods on redox-based signals that uniquely span communication modalities. There are three specific aims in the proposed work. In Aim 1, the PIs will develop actuator devices that transduce electrical inputs to molecular signaling molecules, specifically bacterial quorum sensing autoinducers that regulate behavior. In Aim 2, they will develop sensor devices that communicate in the opposite direction - biomolecular information will be converted to electrical outputs. The researchers will determine molecular concentrations electronically, both directly and with the aid of enzymes and engineered cells that are incorporated into the devices. In Aim 3, these sensor/actuator modules will be integrated into a complete "animal-on-a-chip" system. Using this modular approach, the complexity of the current systems will be reduced, the throughput of these devices will be increased, and the efficiency of the entire process will be dramatically enhanced. The PIs expect these studies will vastly improve our ability to understand the ?communication? between molecules, cells, and tissues in the human body. Most importantly, the proposed work creates a new vantage point for interrogating biology at the length and time scales associated with its function. Equally importantly, because these systems incorporate techniques and methods from several disciplines, and because the perceived benefits to society are so great, they attract energetic and talented students who will become the innovators and leaders of the future.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.