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Many a researcher has experienced that uncomfortable shaking of the hand at the moment of placing a precious cell sample in the flow cytometer. Many have also come to the painful realization that if the sample has less than a few hundred thousand cells, FACS is just not an option. For those frustrated cell sorters, help is likely to come from miniaturization, and the 'FACS-on-a-chip' dream has started to crystallize thanks to microfluidics.

Microfluidic techniques take advantage of the laminar flows adopted by microliters of liquid moving in micron-scale channels. Several groups have already succeeded in sorting cells in such devices by using electric fields or hydrodynamic valves to divert the cell flow into different microchannels. However, these devices remain mostly impractical for the manipulation of fragile mammalian cells. In a recent report in Nature Biotechnology, a group led by William Butler at the San Diego–based company Genoptix announces that they have achieved a big step forward by sorting HeLa cells on a microfluidic chip using the forces of a focused light beam (Wang et al., 2005). In the new device, a narrow stream of cells in a microchannel goes through an analysis region, then through an 'optical switch' region situated just before a Y-shaped junction, where the flow splits between two microchannels. If a fluorescent cell is detected in the analysis region, the optical switch is turned on and the cell is moved within the flow so that it is directed down the 'collection' branch of the Y junction.

The main advantage of this optical switch is the rapid response as the cells are moved within the laminar flow, relative to approaches relying on transient changes to the fluid flow. The result is a major improvement in purity and yields. To make the optical switch efficient, Butler explains, they had to use a 20-watt laser and this high power, in turn, necessitated the use of glass microfluidic devices rather than simpler plastic devices. Obviously, implementation remains difficult, but Genoptix intends to commercialize the technology. “[We will] most likely [be] commercializing instruments for sale to the research, industrial and clinical communities as various applications are developed,” says Butler. So steady that shaking hand—help is on the way.