A benchmark study with sealchip planar patch-clamp technology.
Although conventional patch-clamp methods provide high information content, they are labor-intensive and suffer from low throughput and high overall cost. Several approaches for achieving high throughput electrophysiology are under development, among which microchip-based patch-clamp systems uniquely achieve a higher degree of miniaturization, faster perfusion and mixing, and lower reagent cost without losing information content. The goal of this study was to establish a benchmark for our biochip technology with 52 chips tested sequentially. We demonstrate that our microfabrication and processing technology is sufficiently mature to produce a consistent hole size. We further demonstrate high-quality planar whole-cell patch clamping with >75% overall success rate at achieving gigaohm seals, followed by stable whole-cell access lasting at least 15 min with access resistance (Ra) below 15 MOmega and membrane resistance (Rm) above 200 MOmega. These biochips are ideally suited for high throughput compound screening for ion channel targets.
Xu
Jia
J
AVIVA Biosciences Corp, San Diego, CA 92121, USA. jxu@avivabio.com
Guia
António
A
Rothwarf
David
D
Huang
Mingxian
M
Sithiphong
Khachone
K
Ouang
Joe
J
Tao
Guoliang
G
Wang
Xiaobo
X
Wu
Lei
L
D000818:Animals; D019985:Benchmarking / Q000379:methods; D016466:CHO Cells; D018929:Cell Culture Techniques / Q000295:instrumentation* / Q000379:methods; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D004353:Drug Evaluation, Preclinical / Q000295:instrumentation* / Q000379:methods; D004594:Electrophysiology / Q000295:instrumentation / Q000379:methods; D004867:Equipment Design; D019544:Equipment Failure Analysis; D005240:Feasibility Studies; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology*; D008839:Microelectrodes; D018408:Patch-Clamp Techniques / Q000295:instrumentation* / Q000379:methods; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D024683:Potassium Channels, Tandem Pore Domain; D015203:Reproducibility of Results; D012371:Robotics / Q000295:instrumentation* / Q000379:methods; D012680:Sensitivity and Specificity
D007473:Ion Channels; D015221:Potassium Channels; D024683:Potassium Channels, Tandem Pore Domain