Membrane protein biosensor with multi-channel CMOS impedance extractor and digitizer

Recent advances in the self-assembly of biomimetic interfaces permit the development of biosensor arrays that harness the unique sensitivity and selectivity of membrane proteins. Integrating these interfaces into microsystem platforms for point-of-care and high throughput screening applications requires compact, multi-channel readout circuitry to measure interface impedance over a broad frequency spectrum. This paper described the design and characterization of a biosensor array microsystem comprised of a new CMOS impedance extractor and digitizer (IED) circuit and tethered bilayer lipid membranes (tBLM) incorporated with gramicidin ion channel proteins. The extremely hardware efficient mixed-signal IED circuit measures the response of a tBLM interface, extracts its real and imaginary impedance components, and digitizes and stores the results. Occupying only 0.06 mm², the IED circuit can be instantiated more than 100 times in a single 3 mm times 3 mm chip, making it well suited for simultaneous readout of a variety of monolithic sensor arrays.