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Issue 10, 2007
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Microfluidic integration of substantially round glass capillaries for lateral patch clamping on chip

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Abstract

High-throughput screening of drug candidates for channelopathies can greatly benefit from an automated patch-clamping assay. Automation of the patch clamping through microfluidics ideally requires on-chip integration of glass capillaries with substantially round cross section. Such round capillaries, if they can only be integrated to connect isolated reservoirs on a substrate surface, will lead to a “lateral” configuration which is simple yet powerful for the patch clamping. We demonstrate here “lateral” patch clamping through microfluidic integration of substantially round glass capillaries in a novel process. The process adopts two well-known phenomena from microelectronics: keyhole-void formation and thermal-reflow of phosphosilicate glass in silicon trenches. The process relies on the same physical principle as the preparation of conventional micropipette electrodes by heat-pulling and fire-polishing glass tubes. The optimized process forms capillaries with a diameter ∼1.5 µm and variation <10%. Functionality of the integrated glass capillaries for the patch-clamp recording has been verified by statistical test results from a sample of one hundred capillaries on mammalian cells (RBL-1) in suspension: 61% formed gigaseals (>1 GΩ) and of those ∼48% (29% of all) achieved whole-cell recordings. Pharmacological blockade of ion channel activity and longevity of a whole-cell mode on these capillaries have also been presented.

Graphical abstract: Microfluidic integration of substantially round glass capillaries for lateral patch clamping on chip

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Article information


Submitted
17 May 2007
Accepted
25 Jun 2007
First published
17 Jul 2007

Lab Chip, 2007,7, 1357-1366
Article type
Paper

Microfluidic integration of substantially round glass capillaries for lateral patch clamping on chip

W. Ong, K. Tang, A. Agarwal, R. Nagarajan, L. Luo and L. Yobas, Lab Chip, 2007, 7, 1357
DOI: 10.1039/B707439E

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