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Chips and More Chips W
hat field do you know that offers research challenges and opportunities in environmental, clinical, and workplace analyses; fluid mechanics, polymer, and materials chemistry; and the arenas of microlithography, separation science, single-cell studies, immunoassays, DNA sequencing, and trace detection? You say it has to be an exceptionally crosscutting topic. It is, but the concept is deceptively simple: Miniaturize the instrument—sample input, pre- and postcolumn reaction chambers, separation column, and detector—onto a single, small structure. This Frontiers Editorial salutes the “lab-on-a-chip” concept and the research progress, much of it reported in this Journal, that over the past decade has made the technique a major force in analytical chemistry. Miniaturizing analytical instruments is actually a long-standing trend. Major diminutions in physical dimensions have accompanied improvements in optics, light sources (lasers), durable polymeric components, microelectronic- and computer-based control and recording functions, microelectrodes, and piezoelectric elements, among others. The essential features of the lab on a chip, or “analytical microchip” as I personally refer to it, exploit modern microfabrication technology to fashion the part of the instrument that contains the analyte and reagent solutions into a monolithic block, disk, or plate. The geometry of the microcontainer depends on how the fluids are to be set in motion; manipulated and mixed; reacted in chambers; separated in tiny columns by chromatographic, electrophoretic, or other principles; and detected. The key microchip issue is, of course, how do you make it? At what dimensions can you make it? Are its materials friendly to the analytical processes? Can you afford it? The seminal step was taken in the late 1970s at Stanford University, where researchers used microlithography to form a GC column on a silicon wafer. That early idea lay fallow for many years, in part because of the relative inaccessibility of lithographic technology, until 1990, when Manz and co-workers etched an open tubular liquid chromatography column into a 5 5-mm Si chip and shortly afterwards proposed the lab-on-a-chip idea. Microchip fabrication has grown increasingly sophisticated, with the variety of chemical materials used and the chemical attributes that can now be designed into them. The electrical
double layer has been rediscovered, and some realize that it is poorly understood at polymer surfaces. Microfluidics, the fluid dynamics of solutions in micrometer-scale channels and pores, has become a significant analytical microchip research topic. It is now not unusual for Analytical Chemistry to receive manuscripts from authors in departments of mechanical engineering! The second level of developing analytical microchips is to graft other instrument components onto them, such as sampling stages, sample inlets, pumps, valves, mixers, heaters, coolers, magnetic stages, detectors, and fraction collectors. To make autonomous devices, a third stage of development incorporates the electronics control and recording functions onto the chip. At these very rapidly expanding levels, microchips cut across an enormous cross section of analytical and materials chemistries. The microchip design and its appurtenances become oriented towards the actual applications, which are very diverse. There is, for example, no incentive to develop a microchip aimed at one-shot clinical analyses, beyond giving its surfaces some desired chemical functionality and providing connections for analytical detection, such as fluorescence or MS. Multiplexing is very attractive with microchips; it is possible to microfabricate >300 electrophoretic separation microchannels for parallel sequencing analysis. A microchip may be designed for flow-through sampling and immunoseparation for protein purification, concentration, and detection, or for flow-through organic reactions at timed, controlled temperatures. This diversity of application directions gives microchips their current appeal for research and commercialization. Space does not permit mentioning more than a tiny fraction of the analytical microchip field. For further reading, I recommend two very lucid reviews by Manz and associates in the June 15 issue of Analytical Chemistry. This topic has such probable future impact that textbook writers should start preparing chapters on it for their next editions. Analytical Chemistry continues to welcome manuscripts addressing all phases of analytical microchip research.
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