Bacteria have adopted for life in every corner of our planet by, among other, developing a remarkable portfolio of sensing capabilities. A compelling area of Synthetic Biology recognized the sensing potential of bacteria and, relying on our increasing capacity to synthesize and insert desired genetic information into the living cells, aims to exploit the current and provide a new range of biological sensing modalities.
The sensor industry sees great promise in such whole-cell based biosensors, with interest in a diverse and large set of different targets: from toxins, pathogens and explosives to human-health related markers. While a range of different bacterial whole-cell based biosensors have been reported, we have yet to develop a suitable bioelectrical interface, which is a key barrier that limits the reliable and feasible application of biosensors in a range of different external environments. Specifically, the most common output signal of existing bacterial whole-cell biosensors is light. Yet, the current sensor industry relies heavily on silicon-based microelectronics and is interest in biosensors with electrogenic outputs that would enable efficient incorporation into the existing manufacturing capabilities. To overcome this key limitation, in this project we wish to develop a novel biohybrid electronic device architecture that can be used for environmental and physiological sensing.
The biohybrid architecture will allow sensing on the single-cell level, yet on thousands of cells at the same time. The design of the single-cell based biosensor with electrical output (a biochip) is based on the rotation of the bacterial flagellar motor (BFM). The motor is a unique rotary molecular machine that has captivated scientists for several decades. The evolutionary function of the motor is to enable propulsion of the bacterium by rotating the flagellum attached to it. Like an electric motor, the BFM has a rotor and a stator, made of several protein rings, that protrude from the cytoplasm through the entire cell envelope. Ordinarily, the rotational direction of the motor is controlled by the chemotactic network, but in this project, we will gain control of the rotational direction and modify the cells in a way that will allow us to use the frequency of the BFM's rotational direction changes with synthetic biology tools. This will allow us to design cells that sense molecule in the environment and in response to the concentration in the environment, change the frequency of the rotational direction changes of the motor. Next, we will detect the motor rotation electrically, using an integrated chip and small electrodes that are the size of the bacterial cells.
In conclusion, we will design an electrical biochip that will enable us to push the limits of whole cell biosensing beyond currently achievable.
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