Microfluidics platform for single-shot dose-response analysis of chloride channel-modulating compounds

Byung Ju Jin, Eun A. Ko, W. Namkung, A. S. Verkman

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

We previously developed cell-based kinetics assays of chloride channel modulators utilizing genetically encoded yellow fluorescent proteins. Fluorescence platereader-based high-throughput screens yielded small-molecule activators and inhibitors of the cAMP-activated chloride channel CFTR and calcium-activated chloride channels, including TMEM16A. Here, we report a microfluidics platform for single-shot determination of concentration-activity relations in which a 1.5 × 1.5 mm square area of adherent cultured cells is exposed for 5-10 min to a pseudo-logarithmic gradient of test compound generated by iterative, two-component channel mixing. Cell fluorescence is imaged following perfusion with an iodide-containing solution to give iodide influx rate at each location in the image field, thus quantifying modulator effects over a wide range of concentrations in a single measurement. IC 50 determined for CFTR and TMEM16A activators and inhibitors by single-shot microfluidics were in agreement with conventional plate reader measurements. The microfluidics approach developed here may accelerate the discovery and characterization of chloride channel-targeted drugs.

Original languageEnglish
Pages (from-to)3862-3867
Number of pages6
JournalLab on a chip
Volume13
Issue number19
DOIs
Publication statusPublished - 2013 Oct 7

All Science Journal Classification (ASJC) codes

  • Bioengineering
  • Biochemistry
  • Chemistry(all)
  • Biomedical Engineering

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