Liquid Logic: Tiny plumbing networks concoct and compute

Inspired by microelectronics, scientists have been shrinking the cluttered labware used for chemical and biological studies onto tiny fluid-manipulating chips (SN: 8/15/98, p. 104: Now, a team of California researchers has made two such devices that leap ahead of the others in both complexity and controllability.

MICROPLUMBING. In this microscope image of a so-called comparator, dyes highlight components such as valves (pink, yellow, orange, and green) and fluid channels (dark blue). Thorsen et al./Science

Studded with thousands of wee hydraulic valves that act as the equivalents of transistors and with minute rubbery pipes that serve as wires, the new chips are extraordinarily versatile for carrying out complicated chemical reactions and analyses, the scientists say. Called microfluidic chips, the devices can also store data represented by different fluids and hydraulically execute simple logic operations that are usually left to electronic circuits.

Microfluidic chips of this sophistication promise to improve the speed and accuracy of procedures such as screening cells for disease, says co-inventor Stephen R. Quake of the California Institute of Technology in Pasadena. Quake and his Caltech colleagues Todd A. Thorsen and Sebastian J. Maerkl describe their new chips in an upcoming issue of Science. Each device is about the size of a postage stamp.

Already, Fluidigm of South San Francisco, Calif., which Quake cofounded, is selling a device that uses some features of the new technology for investigating protein crystallization.

Most microfluidic chips devised by other researchers lack on-chip valves. They rely on external valves and other means of controlling fluid motion, notes Scott Manalis of the Massachusetts Institute of Technology. By incorporating so many simple valves into microfluidic chips, the Caltech team has achieved “a tour de force,” he says.

To make their new chips, the researchers optically projected patterns on light-sensitive materials. Then they dissolved away the exposed regions to create molds, which they used to cast the minuscule plumbing designs in silicone rubber. “The final device is all rubber,” Quake says.

One of the Caltech team’s two new chips contains a close-packed array of 1,000 tiny chambers that can each hold 250 trillionths of a liter of fluid. Within the chip’s elaborate plumbing network, every chamber can be independently filled or emptied. Such direct access to every element is also a feature of electronic random-access memory chips, the researchers note.

With the second chip–dubbed a comparator, which is also a type of electronic circuit–the researchers demonstrated that they could isolate single bacteria in different chambers, test the microbes for production of a particular enzyme, and then evacuate selected microbes from the device. To simplify control, the researchers arrange a few valves in patterns called multiplexors that enable them to turn on or off many channels.

Although the new chips are highly complex, they’re just a starting point, Quake claims. He predicts that designs like these will serve as components of a more elaborate microfluidic system.

“Piece by piece, we’re putting it together,” Quake says.


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