Noise Optimization for High-Bandwidth Ion Channel Recordings

Single-molecule measurements often exhibit weak signals and fast kinetics, making them particularly challenging to record with high fidelity. This thesis presents an analysis of voltage-clamp current recordings of single ion channels, and concludes that considerable improvements in signal-to-noise ratios can be achieved by minimizing all parasitic capacitances associated with these measurements. A custom integrated amplifier in a 0.13-micron complementary metal oxide semiconductor (CMOS) process is designed for high-bandwidth ion channel recordings, and systems are designed to closely incorporate this amplifier with solid-state nanopore sensors, lipid membranes, and biological ion channels. The low capacitance of these integrated platforms reduces noise at high frequencies, enabling signals to be measured up to ten times faster than had been previously achieved. In addition to improving signal quality, the small physical size of these integrated systems portends the arrival of massively parallel high-performance ion channel recording systems for drug discovery and biomolecular sensing applications.