Dynamic ion channel activation scheduling in patch clamp on a chip.

Abstract

In 2002, Fertig et al. made a remarkable invention: the first successful demonstration of a patch clamp on a chip--a planar quartz-based biological chip that contains up to several hundred ion channels. This patch-clamp chip can be used in massively parallel screens for ion channel activity, thereby providing a high-throughput screening tool for drug discovery efforts. In this paper, we propose computationally efficient dynamic stochastic scheduling algorithms for activating individual ion channels in the patch-clamp chip. By formulating the ion channel activation scheduling problem as a partially observed Markov decision process with a multiarmed bandit structure, near-optimal dynamic scheduling for activation of the individual channels is achieved to optimize the information gained from the patch-clamp chip. Numerical examples using state-of-the-art algorithms developed recently in artificial intelligence and operations research are presented to illustrate these dynamic ion channel (macromolecule) activation scheduling algorithms.