J A N U A R Y 1 , 2 0 0 3 / A N A LY T I C A L C H E M I S T R Y 5 A

e d i t o r i a l

Chips and More Chips

What field do you know that offers research challenges andopportunities in environmental, clinical, and workplace

analyses; fluid mechanics, polymer, and materials chemistry; andthe arenas of microlithography, separation science, single-cellstudies, 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 instru-ment—sample input, pre- and postcolumn reaction chambers,separation column, and detector—onto a single, small struc-ture. This Frontiers Editorial salutes the “lab-on-a-chip” con-cept and the research progress, much of it reported in thisJournal, that over the past decade has made the technique amajor force in analytical chemistry.

Miniaturizing analytical instruments is actually a long-standingtrend. Major diminutions in physical dimensions have accompa-nied improvements in optics, light sources (lasers), durable poly-meric components, microelectronic- and computer-based controland recording functions, microelectrodes, and piezoelectric ele-ments, among others. The essential features of the lab on a chip,or “analytical microchip” as I personally refer to it, exploit mod-ern microfabrication technology to fashion the part of the in-strument that contains the analyte and reagent solutions intoa monolithic block, disk, or plate. The geometry of the mi-crocontainer depends on how the fluids are to be set in mo-tion; manipulated and mixed; reacted in chambers; separatedin tiny columns by chromatographic, electrophoretic, or otherprinciples; and detected.

The key microchip issue is, of course, how do you make it?At what dimensions can you make it? Are its materials friendlyto the analytical processes? Can you afford it? The seminal stepwas taken in the late 1970s at Stanford University, where re-searchers used microlithography to form a GC column on asilicon wafer. That early idea lay fallow for many years, in partbecause of the relative inaccessibility of lithographic technolo-gy, until 1990, when Manz and co-workers etched an open tu-bular liquid chromatography column into a 5 � 5-mm Si chipand shortly afterwards proposed the lab-on-a-chip idea.

Microchip fabrication has grown increasingly sophisticated,with the variety of chemical materials used and the chemicalattributes that can now be designed into them. The electrical

double layer has been rediscovered, and some realize that it ispoorly understood at polymer surfaces. Microfluidics, the fluiddynamics of solutions in micrometer-scale channels and pores,has become a significant analytical microchip research topic. Itis now not unusual for Analytical Chemistry to receive manu-scripts from authors in departments of mechanical engineering!

The second level of developing analytical microchips is tograft other instrument components onto them, such as sam-pling stages, sample inlets, pumps, valves, mixers, heaters, cool-ers, magnetic stages, detectors, and fraction collectors. To makeautonomous devices, a third stage of development incorporatesthe electronics control and recording functions onto the chip.At these very rapidly expanding levels, microchips cut across anenormous cross section of analytical and materials chemistries.The microchip design and its appurtenances become orientedtowards the actual applications, which are very diverse.

There is, for example, no incentive to develop a microchipaimed at one-shot clinical analyses, beyond giving its surfacessome desired chemical functionality and providing connectionsfor analytical detection, such as fluorescence or MS. Multiplex-ing is very attractive with microchips; it is possible to micro-fabricate >300 electrophoretic separation microchannels forparallel sequencing analysis. A microchip may be designed forflow-through sampling and immunoseparation for protein pu-rification, concentration, and detection, or for flow-throughorganic reactions at timed, controlled temperatures. This di-versity of application directions gives microchips their currentappeal for research and commercialization.

Space does not permit mentioning more than a tiny fractionof the analytical microchip field. For further reading, I recom-mend two very lucid reviews by Manz and associates in the June15 issue of Analytical Chemistry. This topic has such probablefuture impact that textbook writers should start preparing chap-ters on it for their next editions. Analytical Chemistry continuesto welcome manuscripts addressing all phases of analytical mi-crochip research.