Microsystems for cell-based electrophysiology

Among the electrophysiology techniques, the voltage clamp and its subsequent scaling to smaller mammalian cells, the so-called patch clamp, led to fundamental discoveries in the last century, revealing the ionic mechanisms and the role of single-ion channels in the generation and propagation of action potentials through excitable membranes (e.g. nerves and muscles). Since then, these techniques have gained a reputation as the gold standard of studying cellular ion channels owing to their high accuracy and rich information content via direct measurements under a controlled membrane potential. However, their delicate and skill-laden procedure has put a serious constrain on the throughput and their immediate utilization in the discovery of new cures targeting ion channels until researchers discovered 'lab-on-a-chip' as a viable platform for the automation of these techniques into a reliable high-throughput screening functional assay on ion channels. This review examines the innovative 'lab-on-a-chip' microtechnologies demonstrated towards this target over a period of slightly more than a decade. The technologies are categorically reviewed according to their considerations for design, fabrication, as well as microfluidic integration from a performance perspective with reference to their ability to secure G Ω seals (gigaseals) on cells, the norm broadly accepted among electrophysiologists for quality recordings that reflect ion-channel activity with high fidelity. (topical review)