Microfluidic gradient-generating device for pharmacological profiling.
We describe an on-chip microfluidic gradient-generating device that generates concentration gradients spanning nearly 5 orders of magnitude starting from a single concentration. The exiting stream of drugs held at different concentrations remains laminar in a recording chamber and can be presented as 24 discrete solutions to a cell-based sensor. The high-performance characteristics of the device are demonstrated by pharmacological screening of voltage-gated K+ channels (hERG) and ligand-gated GABA(A) receptors using scanning-probe patch-clamp measurements. Multiple data point dose-response curves and IC50 and EC50 values were rapidly obtained, typically in less than 30 min, through its combined functionality of gradient generation and open-volume laminar flow. The device facilitates rapid pharmacological profiling of ion channel and GPCR effectors and enables the acquisition of large numbers of data points with minute sample consumption and handling.
Pihl
Johan
J
Department of Chemistry and Bioscience, and Microtechnology Centre, Chalmers University of Technology, SE-412 96 Göteborg, Sweden.
Sinclair
Jon
J
Sahlin
Eskil
E
Karlsson
Mattias
M
Petterson
Fredrik
F
Olofsson
Jessica
J
Orwar
Owe
O
D000818:Animals; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D004353:Drug Evaluation, Preclinical / Q000295:instrumentation* / Q000379:methods*; D000072237:ERG1 Potassium Channel; D004563:Electrochemistry / Q000295:instrumentation / Q000379:methods; D051638:Ether-A-Go-Go Potassium Channels / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation*; D018408:Patch-Clamp Techniques / Q000295:instrumentation / Q000379:methods; D018079:Receptors, GABA / Q000737:chemistry / Q000378:metabolism
D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C000606913:KCNH2 protein, human; D018079:Receptors, GABA