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Microfluidic integration of substantially round glass capillaries for lateral patch clamping on chip
W.-L. Ong, K.-C. Tang, , R. Nagarajan, L.-W. Luo, L. Yobas
Published in Royal Society of Chemistry
PMID: 17896022
Volume: 7
Issue: 10
Pages: 1357 - 1366
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. © The Royal Society of Chemistry.
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JournalData powered by TypesetLab on a Chip
PublisherData powered by TypesetRoyal Society of Chemistry