Cellectricon's Dynaflow patch-clamp system combines microfluidics and patch-clamping technology. Credit: CELLECTRICON

Although most patch-clamp technologies seek to maximize the number of cells rushed through the system, Owe Orwar and his colleagues at Cellectricon, a start-up company based in Gothenburg, Sweden, have developed a platform that maximizes the information gained from each cell. The result is a powerful tool for secondary screening in drug discovery. Their Dynaflow technology uses conventional glass pipette patch clamping, in combination with a novel microfluidic device for controlled delivery of drug solutions.

Solutions of drugs or drug combinations are placed in up to 48 wells, each of which is connected to a measurement chamber by micrometre-diameter channels. These solutions can be directed through the chamber with high precision. “Dynaflow uses the unique properties of fluids when they are running at very low Reynolds numbers. When the fluids come out from a tiny channel in the open volume they behave as if they are still in channels — they do not mix,” says Orwar.

With no turbulence, diffusion would be the only chance of mixing between solution batches, but the timescales used are too short for that to occur. Consequently, Dynaflow can provide step changes in drugs or drug concentrations, with a change every 30 milliseconds if desired. “It is the most precise technology in the world to titrate receptors,” claims Orwar. “You can see it as a microfluidic device that generates a barcode of chemicals, and the cell effectively reading the barcode,” he adds.

The ability to squeeze so much data out of a single cell enables some users to claim a ten-fold increase in productivity. By using carefully considered combinations of drugs in each well, cells can be taken through physiologically relevant conditions that relate to many different disease states. “In effect, it gives you the option of passing a chemical waveform over the cell while constantly recording from it,” says Orwar.

P.M.