A microfluidic device for measuring cellular membrane potential

Recent developments in microfluidics have enabled the design of a lab-on-a- chip system capable of measuring cellular membrane potential. The chip acce sses liquid samples sequentially by sipping from a microplate through a cap illary, mixes the samples with cells flowing through a microchannel, contac ts the cells with potential-sensitive dyes, and reads out cellular response s using fluorescence detection. The rate of cellular uptake of membrane-per meable, ionic fluorophores by THP-I cells was found to depend strongly on m embrane potential. The ratio of the fluorescence of the anionic dye DiBAC(4 )(3) and the cationic dye Syto 62 taken up by cells was found to double for every 33 mV change in membrane potential. The utility of this approach was demonstrated by assaying ion channel activity in human T lymphocytes. Beca use of the high sensitivity, low cellular and reagent consumption, and high data quality obtained with the microfluidic device, the lab-on-a-chip syst em should be widely applicable in high-throughput screening and functional genomics studies. (C) 2001 Academic Press.