Fast solution exchange microfluidic device for kinetic analysis of single cells

We are developing a novel fast solution exchange microfluidic device constructed from poly(dimethylsiloxane) for the kinetic analysis of single cells. The lateral cell trapping junctions enable hydrodynamic placement of a single cell from the bulk cell suspension and nano-fluidic injection sites enable fast and precise delivery of picoliter volume of reagents to that cell.

Our setup facilitates studying kinetics of ligand-gated ion channels. Change of concentration of ion, neurotransmitters or of all possible sort of ligands to be tested is an important issue in modern patch-clamp recordings. In addition this device can be used as a single-cell detector which combines the natural signal amplification of whole-cell biosensors with the flexibility and specificity of immunological recognition.

Central to this setup is an injection system that mimics the operation of a controllable, two-way solenoid valve. Analyte and carrier solutions continuously flow through this injection system allowing for measurements and sample changes to be performed rapidly and simultaneously.

A) Schematic drawing of fast solution exchange microfluidic device for kinetic analysis of single cells. B) Photograph of the microfluidic device. Cells in suspension are loaded from the main fluidic channel and get trapped from the lateral cell trapping junctions. C) Optical image of trapped cells

References:

J. Seo, C. Ionescu-Zanetti, J. Diamond, R. Lal, and L. P. Lee, "Integrated multiple patch-clamp array chip via lateral cell trapping junctions", Applied Physics Letters., 84, 1973 (2004).

F. Sachs, "Practical Limits on the Maximal Speed of Solution Exchange for Patch Clamp Experiments", Biophysical Journal , 77 August 199

A. R Wheeler, W. R. Throndset, R. J. Whelan, A. M. Leach, R. N. Zare, Y. H. Liao, K. Farrell, I. D. Manger, A. Daridon, "Microfluidic Device for Single-Cell Analysis," Anal. Chem. 75, 3581-3586 (2003).