Automated electrophysiology: high throughput of art.

Electrophysiological measurements, in particular, patch clamping, have long been regarded as the "gold standard" for assaying ion channels. Despite its high information content, the technique suffers from laborious, manual processing by highly skilled workers and extremely low throughput. Recently, a number of researchers have started to automate patch clamping by either automating conventional micropipette-based patch clamping or developing planar microelectrode arrays. This article reviews the brief history of these emerging technologies and discusses the technical details, advantages, and disadvantages of each approach and technique. As will be evident from the discussion, two types of automated patch-clamping technologies are emerging. The first places emphasis on data quality, comparable to conventional patch clamping, and the second has much higher throughput. Future developments will include sophisticated patch-clamping devices with both high-quality data and high throughput capabilities and further integration of patch clamping with other cell-based assays.

[1]  A. Hodgkin,et al.  A quantitative description of membrane current and its application to conduction and excitation in nerve , 1990 .

[2]  Brian Cox,et al.  HTS approaches to voltage-gated ion channel drug discovery , 1998 .

[3]  N. Fertig,et al.  Activity of single ion channel proteins detected with a planar microstructure , 2002 .

[4]  Margit Asmild,et al.  Upscaling and automation of electrophysiology: toward high throughput screening in ion channel drug discovery. , 2003, Receptors & channels.

[5]  B. Sakmann,et al.  Single-Channel Recording , 1995, Springer US.

[6]  F. Ashcroft Ion channels and disease , 1999, Oxford Textbook of Medicine.

[7]  Jing Cheng,et al.  Electronic Manipulation of Cells on Microchip-Based Devices , 2001 .

[8]  L. Mattheakis,et al.  Assay technologies for screening ion channel targets. , 2001, Current opinion in drug discovery & development.

[9]  Alfred Stett,et al.  CYTOCENTERING: a novel technique enabling automated cell-by-cell patch clamping with the CYTOPATCH chip. , 2003, Receptors & channels.

[10]  Thomas A Nemcek,et al.  High throughput electrophysiology using a fully automated, multiplexed recording system. , 2003, Receptors & channels.

[11]  A. Hodgkin,et al.  Currents carried by sodium and potassium ions through the membrane of the giant axon of Loligo , 1952, The Journal of physiology.

[12]  W. Webb,et al.  Lipid-glass adhesion in giga-sealed patch-clamped membranes. , 1994, Biophysical journal.

[13]  S. P. Fodor,et al.  Light-directed, spatially addressable parallel chemical synthesis. , 1991, Science.

[14]  David P. Corey,et al.  Science and Technology of Patch-Recording Electrodes , 1983 .

[15]  Robert H Blick,et al.  Microstructured apertures in planar glass substrates for ion channel research. , 2003, Receptors & channels.

[16]  A. Hodgkin,et al.  The dual effect of membrane potential on sodium conductance in the giant axon of Loligo , 1952, The Journal of physiology.

[17]  Lei Wu,et al.  Ion-channel assay technologies: quo vadis? , 2001, Drug discovery today.

[18]  O. Krishtal,et al.  Effect of internal fluoride and phosphate on membrane currents during intracellular dialysis of nerve cells , 1975, Nature.

[19]  B. Sakmann,et al.  Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches , 1981, Pflügers Archiv.

[20]  Michael Fejtl,et al.  The roboocyte: automated cDNA/mRNA injection and subsequent TEVC recording on Xenopus oocytes in 96-well microtiter plates. , 2003, Receptors & channels.

[21]  Jeffrey Y. Pan,et al.  High Throughput Electrophysiology Using a Fully Automated, Multiplexed Recording System , 2003 .

[22]  Horst Vogel,et al.  Chip based biosensor for functional analysis of single ion channels , 2000 .

[23]  David Ashkenasi,et al.  Laser-induced microstructuring of dielectrics using ultrashort laser pulses , 1997, CLEO '97., Summaries of Papers Presented at the Conference on Lasers and Electro-Optics.

[24]  C. Trautmann,et al.  Microstructured glass chip for ion-channel electrophysiology. , 2001, Physical review. E, Statistical, nonlinear, and soft matter physics.

[25]  Owe Orwar,et al.  A cell-based bar code reader for high-throughput screening of ion channel-ligand interactions. , 2002, Analytical chemistry.

[26]  A. Lepple-Wienhues,et al.  Flip the tip: an automated, high quality, cost-effective patch clamp screen. , 2003, Receptors & channels.

[27]  P. Christophersen,et al.  High throughput electrophysiology: new perspectives for ion channel drug discovery. , 2003, Receptors & channels.

[28]  M. Reed,et al.  Micromolded PDMS planar electrode allows patch clamp electrical recordings from cells. , 2002, Biosensors & bioelectronics.

[29]  Timothy B. Stockwell,et al.  The Sequence of the Human Genome , 2001, Science.

[30]  Alfred Stett,et al.  CYTOCENTERING: a novel technique enabling automated cell-by-cell patch clamping with the CYTOPATCH chip. , 2003, Receptors & channels.

[31]  Derek J Trezise,et al.  IonWorks™ HT: A New High-Throughput Electrophysiology Measurement Platform , 2003, Journal of biomolecular screening.

[32]  F J Sigworth,et al.  Two-microelectrode voltage clamp of Xenopus oocytes: voltage errors and compensation for local current flow. , 1999, Biophysical journal.

[33]  F Bezanilla,et al.  Bilayer reconstitution of voltage-dependent ion channels using a microfabricated silicon chip. , 2001, Biophysical journal.

[34]  Ling Wang,et al.  Multiplexed, targeted gene expression profiling and genetic analysis on electronic microarrays. , 2002, Clinical chemistry.

[35]  D. Rothwarf,et al.  A benchmark study with sealchip planar patch-clamp technology. , 2003, Assay and drug development technologies.

[36]  Robert H Blick,et al.  Whole cell patch clamp recording performed on a planar glass chip. , 2002, Biophysical journal.

[37]  S. Kubota,et al.  Applications of continuous-wave deep ultraviolet lasers , 1995 .

[38]  A. Hodgkin,et al.  The components of membrane conductance in the giant axon of Loligo , 1952, The Journal of physiology.

[39]  ジェレイント オウエン,デイビッド,et al.  High throughput screen , 1999 .

[40]  Paul B Bennett,et al.  High throughput ion-channel pharmacology: planar-array-based voltage clamp. , 2003, Assay and drug development technologies.

[41]  F. Sigworth,et al.  Patch clamp on a chip. , 2002, Biophysical journal.