A Cyto-silicon Hybrid System with On-chip Closed-loop Modulation.

We introduce a bioelectronic interface between biological electrogenic cells and a mixed-signal CMOS integrated circuit with an array of surface electrodes, where not only is the CMOS electrode array capable of electrophysiological recording and stimulation of the cells with 1,024 recording and stimulation channels, but it can also provide low-latency artificial signal pathways from cells it records to cells it stimulates. This on-chip closed-loop modulation has an intrinsic latency less than 5 μs. To demonstrate the utility of the on-chip closed loop modulation as an artificial feedback pathway between biological cells, we develop a silicon-cardiomyocyte self-sustained oscillator with a tunable frequency to which both the relevant part of the CMOS chip and cells are locked, and also a silicon-neuron interface with a silicon inhibitory connection between neuronal cells. This line of cyto-silicon hybrid system, where the boundary between biological and semiconductor systems is blurred, may find applications in prosthesis, brain-machine interface, and fundamental biology research.