Title: A Hybrid Si-based System for Electrophysiology with low-noise Signal Processing
Speaker:  Prof. Santosh Pandey
Abstract:

Ion channels are proteins located in cell membranes that permit and regulate the movement of ions at a rate of >10⁶ ions/s across a normally impermeable lipid bilayer. These ion channels play important roles in the physiological state of the cell, including rapid signaling, electrical excitability and fluid transport throughout the body. More than 40% of the known human diseases are directly or indirectly related to dysfunctions in ion-channels. At present, a method called patch-clamping is the gold standard for studying ion-channel activity. It provides a complete, microsecond scale control over the electrical and chemical environment of the ion channel. However, the detection of ion channel signals and their processing in a low-noise environment has always been a painstaking and expensive process. New techniques such as combinatorial chemistry and genetics, which produce large numbers of potential drugs and mutant proteins, respectively, demand efficient and reliable high-throughput screening.

In recent years, numerous methods of automated electrophysiology have emerged to overcome the obstacles of manual patch clamping. The talk will describe our research on a miniaturized hybrid planar patch-clamp system for probing ion-channel signals. This system is designed and fabricated using MEMS, microfluidics and CMOS silicon-based technologies. The advantage of this system is the eventual ease of investigating ion-channels as drug targets for medical research. A MEMS micropore membrane structure was built, with attached microfluidics and integrated dielectrophoretic and mechanical forces to isolate and position a single cell automatically over the micropore. A novel CMOS instrumentation amplifier will be described to process the low-level ion-channel signal currents with an ultra-high gain of ~10¹⁰ V/A. Correlated Double Sampling is used for noise suppression and uses a unique integration-discrete differentiation technique to process both whole cell (1-10nA) and single ion-channel currents (5-10pA) at kHz rates. Our work on the simulation of ion transport through a voltage-gated KcsA ion channel using a unique solid-state device simulator will be shown. The model incorporates ion transport factors, such as the interaction between neighboring ions and protein walls, surface charges, and the varying fields. Information about the probability density function and power spectral density of ion number fluctuations can thus be obtained.