anipulating fractions of a microliter of fluid is an accepted part of the new branch of chemistry known as lab-on-a-chip. There are now well-developed chips made up of networks of microplumbing that can transport a droplet of liquid through pipes, valves, reaction chambers, and chromatography devices. Just what might ultimately be achieved in this field is revealed in Hot Paper #5, which describes a remarkable device that promises to transform chemical research, forensic detection, and especially medical diagnosis. The cause of an illness or the progress of medical treatment might soon be deduced from minute droplets of sweat, saliva, and tears.

Paper #5 was the first to demonstrate microfluidic large-scale integrations, which have a complexity of possibilities that the authors compare to those of an electronic integrated circuit. The paper comes from the California Institute of Technology, Pasadena, and was the work of Stephen Quake and his research students Sebastian Maerkl and Todd Thorsen (who is now at MIT). It shows how an integrated microfluidic network can be used to construct a comparator array and storage device whose behavior resembles random-access memory in computers. The Caltech group have made silicone devices with thousands of valves and hundreds of chambers in which different chemical reactions can be carried out. Their chips are made from a silicone elastomer, poly(dimethylsiloxane), and this in itself confers several advantages over lab-chips made of hard materials, not least of which is that it forms tight seals around the steel pins through which fluids are injected into the device.

Paper #5 describes a microfluidic device with a thousand independent compartments, arranged in a 25 x 40 array, and accessed through 3,574 microvalves. The volume of each chamber is 250 pictoliters (= 0.25 nanoliters = 0.00025 microliters). The valve system allows each chamber to be individually primed in isolation from its neighbors. The chip is loaded through a single input port, after which the fluid is manipulated under pressure. The new chips have a degree of sophistication not previously seen, in that they have two successive levels of control, the one to load the complete array of cells, the other to manipulate them individually. Paper #5 demonstrates how chambers can be filled and selectively emptied, and this was done with a buffered blue dye with which they produced a microfluidic display spelling their institution’s full initials: "C I T." A key advantage of the plumbing display is that once the picture is set, the device consumes very little power.

Quake and his students also produced a second device in which more complex manipulations of fluids can be performed. In this, two different chemical reagents can be independently added, mixed, and their product of reaction isolated, making it possible to perform various assays in 256 reaction chambers each requiring amounts of reactants less than a nanoliter. They proved their device worked by loading it with blue and yellow dyes, separately injected, which were directed to compartments where they were allowed to mix to form a brown solution, which could then be purged from individual compartments as required. The contents of purged cells are collected through poly(etheretherketone) tubing which is renowned for having very low adhesion properties. What is perhaps most surprising is that the whole assembly requires only 18 connections to the outside world.

More recently Quake has produced a nanoliter nucleic acid processor (see J.W. Hong, et al., Nature Biotech., 22[4]: 435-9, 2004) and a microfluidic rectifier (see A. Groisman, et al., Phys. Rev. Lett., 92[9]: 094501, 2004). Speaking to Science Watch, he foresees a future that promises to be very exciting: "We believe we now have the tools in hand to automate biology in the same way that integrated circuits allowed the automation of mathematics and computation"—and he is already exploring new applications that have been enabled by these ideas. If, as Quake says, the high-density microfluidic chip reported in #5 is analogous to the integrated circuits first printed on semiconductors in the 1950s, then the future of chemistry and its allied sciences may well be transformed as dramatically as computing was changed in the subsequent decades.