By allowing ions into and out of cells, ion channels play a crucial role in cell metabolism by regulating ion concentrations. Whilst this makes them key drug targets, these membrane-spanning pores respond so rapidly to changes in ion concentration that studying them can be difficult. Now, Elodie Dahan at the Swiss Federal Institute of Technology in Lausanne, and colleagues have addressed the problem using lab-on-a-chip technology.

The disposable chip allows non-invasive electrophysiological measurements

Electrophysiologists evaluate ion channel reactions to drug candidates by measuring resulting changes in the channels' response times. These measurements are often made using the two electrode voltage clamp method, in which the cell is pierced with two microelectrodes to record the membrane cell potentials. Although automated versions are available, the impaling is time-consuming and may harm the cell. Also the measurements can be limited by the time it takes to replace the solution surrounding the cell. If these are much longer than the response time the cell will have already responded before the measurement can be taken.

The Swiss team's answer is a disposable chip for non-invasive electrophysiological measurements. Two different solutions flow into the chip mixing at the centre of a Y-junction. The mixed solution then flows towards a cell held inside the chip and the ion current across the cell membrane is measured. The chip design enables the user to change the solution flowing to the cell whilst maintaining a continuous flow, avoiding abrupt changes in shear force and stress effects on the cell membrane. 

The team modified frog egg cells to express ENaC, a human sodium channel, which is involved in sodium transport in the kidneys and airways, and linked to conditions such as cystic fibrosis and hypertension. They then monitored the channel's response to sodium ion concentration by placing the egg cells in the chip and rapidly exchanging a sodium-free solution for a sodium ion solution and recording the current across the membrane over time. The device showed an order of magnitude improvement over conventional techniques.

Daniel Irimia of Massachusetts General Hospital, Boston, US, who develops microfluidic devices for biological and clinical sciences, says the device is a 'wonderful example of how emerging technologies based on microfluidic principles enable more precise, quantitative measurements in biology.' 

Dahan explains that the chip's design should allow other, more complicated experiments to investigate other ion channels. 'The possibility of investigating fast kinetic events of drug receptors with increased throughput overcomes classical bottlenecks and will open the way for such systems to be used in pharmacological laboratories,' she says.

Vikki Chapman