Living cells are equipped with highly versatile built-in toolkits of DNA, RNA, and proteins for molecular communication, computing, storage, and sensing/actuation in response to environmental stimuli. Synthetic biology has been successful in developing engineered cells by harnessing the same biological toolkits with enhanced natural functions or new human-defined functions. These engineered cells can potentially serve as a biological frontend layer that naturally interfaces with the environment and acts as biosensors/actuators, molecular computing platforms, and molecular memory to provide revolutionary solutions for many global challenges such as environmental monitoring, and healthcare. In parallel, with decades of technological advances, semiconductor technologies, e.g., Complementary-Metal-Oxide-Semiconductor (CMOS) integrated circuits (ICs), are being widely employed as a semiconductor backend layer to achieve various integration, communication, and computation capabilities. This project investigates the development of a hybrid programmable nano-bioelectronic system as a first proof-of-concept demonstration that harnesses both the exquisite synthetic functionalities of engineered bacteria as the "biological frontend" and the full functionalities of the ultra-low-power CMOS integrated circuit chips as the "semiconductor backend." The target application of such a system includes in-field biological sensor for environment monitoring. The project has potentials for long-term broader impacts on basic science, education, and technology. It brings expertise from synthetic biology, hybrid bioelectronics, integrated circuits/packaging, information theory, and computing. The project directly addresses three research themes of the solicitation: Theme-1, biomolecular memory and computation; Theme 2, interface of biology and semiconductors; Theme-4, hybrid semiconductor-biological microelectronic systems. It seeks to foster collaborations between industry and academia and hence facilitates technology transfer. The team of investigators will train graduate and undergraduate students at Georgia Tech and MIT, including minority and under-represented students. The project will also emphasize K-12 outreach to promote education of local minority high school students. In particular, the research team will recruit high school teacher interns to enhance their curricula and organize lab tours for K-12 students. The research results will be disseminated through high-impact journals, premier conferences, websites, and social media, and will be integrated into multiple related courses at Georgia Tech and MIT.

The project aims to advance the science in multiple fronts and develop an integrated hybrid programmable nano-bioelectronic system. In such a system, a variety of bacteria strains are engineered as sensing, storage, and computation biological frontends to (1) perform wide-spectrum chemical sensing, e.g., heavy metal detections for environmental monitoring, (2) provide in-bacteria DNA-based storage of analog/digital information, (3) execute molecular computation via stochastic computing and encode the signal for the DNA storage, and (4) support "variable gain" reprogramming of bacteria sensors by external optical and electrical stimuli. As the integrated semiconductor electronics backend, CMOS IC chips with on-chip pixelated massively paralleled arrays will be developed to provide two-way multi-modal interfaces with the bacteria frontends, i.e., for reading stored sensory information from the bacteria and writing control signals to reprogram the bacteria sensors. The bacteria strains and CMOS ICs will be integrated together in 3D-printed microfluidics structures and packages with separate chambers. The proposed components and systems will be demonstrated through in vitro experiments using the resources at Georgia Tech and MIT.

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.

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Georgia Tech Research Corporation
United States
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