Mammalian electrophysiology on a microfluidic platform

doi:10.1073/pnas.0503418102

Mammalian electrophysiology on a microfluidic platform

^*Department of Bioengineering, University of California, Berkeley, CA 94720; ^‡Howard Hughes Medical Institute and Department of Physiology and Biochemistry, University of California, San Francisco, CA 93143-0725; and ^§Division of Cardiology, Department of Medicine, University of California, San Francisco, CA 93143-0124

Contributed by Lily Y. Jan, April 25, 2005

Abstract

The recent development of automated patch clamp technology has increased the throughput of electrophysiology but at the expense of visual access to the cells being studied. To improve visualization and the control of cell position, we have developed a simple alternative patch clamp technique based on microfluidic junctions between a main chamber and lateral recording capillaries, all fabricated by micromolding of polydimethylsiloxane (PDMS). PDMS substrates eliminate the need for vibration isolation and allow direct cell visualization and manipulation using standard microscopy. Microfluidic integration allows recording capillaries to be arrayed 20 μm apart, for a total chamber volume of <0.5 nl. The geometry of the recording capillaries permits high-quality, stable, whole-cell seals despite the hydrophobicity of the PDMS surface. Using this device, we are able to demonstrate reliable whole-cell recording of mammalian cells on an inexpensive microfluidic platform. Recordings of activation of the voltage-sensitive potassium channel Kv2.1 in mammalian cells compare well with traditional pipette recordings. The results make possible the integration of whole-cell electrophysiology with easily manufactured microfluidic lab-on-a-chip devices.

Footnotes

↵ ¶ To whom correspondence may be addressed at: Department of Physiology and Biochemistry, University of California, 1550 Fourth Street, Room GD 484, San Francisco, CA 94143-0725. E-mail: gkw{at}itsa.ucsf.edu.
↵ ∥ To whom correspondence may be addressed at: Department of Bioengineering, University of California, 485 Evans Hall, No. 1762, Berkeley, CA 94720. E-mail: lplee{at}socrates.berkeley.edu.
↵ † C.I.-Z. and R.M.S. contributed equally to this work.
Author contributions: C.I.-Z., R.M.S., J.S., Y.-N.J., L.Y.J., and L.P.L. designed research; C.I.-Z., R.M.S., and J.S. performed research; C.I.-Z., R.M.S., Y.-N.J., L.Y.J., and L.P.L. analyzed data; and C.I.-Z. and R.M.S. wrote the paper.
Abbreviations: PDMS, polydimethylsiloxane; TEA, tetraethylammonium; MΩ, megaohms.