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Microfluidic gradient-generating device for pharmacological profiling.

Johan Pihl1, Jon Sinclair, Eskil Sahlin

  • 1Department of Chemistry and Bioscience, and Microtechnology Centre, Chalmers University of Technology, SE-412 96 Göteborg, Sweden.

Analytical Chemistry
|July 1, 2005
PubMed
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This study introduces a microfluidic device for rapid drug screening. It efficiently generates precise concentration gradients to profile ion channels and receptors, enabling quick dose-response analysis.

Area of Science:

  • Biomedical Engineering
  • Pharmacology
  • Analytical Chemistry

Background:

  • Accurate drug screening requires precise control over compound concentrations.
  • Existing methods for generating concentration gradients can be time-consuming and require large sample volumes.

Purpose of the Study:

  • To develop and validate an on-chip microfluidic device for generating precise and wide-range concentration gradients.
  • To demonstrate the device's utility in rapid pharmacological profiling of ion channels and receptors.

Main Methods:

  • Development of an on-chip microfluidic gradient generator.
  • Utilizing laminar flow in a recording chamber to present discrete drug solutions.
  • Employing scanning-probe patch-clamp measurements for cell-based sensing.

Related Experiment Videos

  • Pharmacological screening of voltage-gated potassium channels (hERG) and ligand-gated GABA(A) receptors.

    • Main Results:

    • The device generates concentration gradients spanning nearly 5 orders of magnitude from a single concentration.
    • Rapid acquisition of multiple data point dose-response curves (IC50 and EC50 values) in under 30 minutes.
    • Successful pharmacological profiling of hERG and GABA(A) receptors was demonstrated.

    Conclusions:

    • The microfluidic device enables high-throughput, rapid pharmacological profiling.
    • It significantly reduces sample consumption and handling time for drug screening.
    • This technology facilitates efficient acquisition of dose-response data for ion channel and GPCR effectors.