A monolithic patch-clamping amplifier with capacitive feedback.
Patch-clamping is an established method for directly measuring ionic transport through cellular membranes with sufficient resolution to observe open/close transitions of individual channel molecules. This paper describes an alternative technique for patch-clamping which uses a capacitor as the transimpedance element. This approach eliminates bandwidth and saturation limitations experienced with resistive patch-clamping amplifiers. A complete monolithic design featuring an on-chip operational amplifier, a capacitor array with gain-ranging from 30 pF down to 0.03 pF, and reset and gain ranging switches has been fabricated using 5 microns CMOS technology. It is shown that the voltage noise of the CMOS operational amplifier limits the overall noise performance, but that performance competitive with conventional instruments can be achieved over a 10 kHz bandwidth, at least for small input capacitances (less than or equal to 5 pF). Results are presented along with an analysis and comparison of noise performance using both resistive and capacitive elements.