Pure Appl. Chem., Vol. 74, No. 12, pp. 2299–2309, 2002. © 2002 IUPAC 2299 Integrated chemical systems on microchips for analysis and assay. Potential future, mobile high-performance detection system for chemical weapons* Yoshikuni Kikutani 1 , Manabu Tokeshi 1 , Kiichi Sato 2 , and Takehiko Kitamori 1,2,‡ 1 Integrated Chemistry Project, Kanagawa Academy of Science and Technology, KSP Bldg, East 307, 3-2-1 Sakado, Takatsu-ku, Kawasaki, Kanagawa 213-0012, Japan; 2 Department of Applied Chemistry, School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan Abstract: By analogy to unit operations (e.g., mixers, reactors, etc.) used in conventional chemical engineering, the concept of microunit operations permits the integration of com- plicated chemical systems onto a small microchip. A protocol for fabrication of such microchips is described, and its use is illustrated in several examples. In addition, the ther- mal lens microscope, which determines nonfluorescent species at the single-molecule level, is indispensable as an ultrasensitive detector for general use. Applications of microchip tech- nology are given for chemical analysis, immunoassay, and full bioassay. Microchip analysis can provide very large enhancements in sensitivity and substantial reductions in measure- ment time as compared with conventional analytical methods. INTRODUCTION High-performance analytical technology may serve as one of the most effective tools to alleviate the menace of chemical weapons (CW), which, in the worst cases, can affect humans from tens of kilome- ters away, are invisible and unscented, and do not reveal their symptoms until a few days afterward. Recent development in microchemical technology enables us to integrate even a complicated chemical system onto a small microchip [1–9]. Microchemical technology is applicable to a wide range of chemical processes, including analyses [2–5], bioassays [2,3,6], and chemical syntheses [7–9]. The merit of the microintegration is that we can use rapid, efficient, and sophisticated chemical technolo- gies anytime and anywhere as the occasion demands. That is, mobile and high-performance analytical systems will be realized in the near future. We cannot deal with CW and biological weapons (BW) attacks by conventional huge and complicated analyzers in analytical centers, because samples must be transferred from the actual spot to laboratories and it usually takes hours or days for these machines to show the results of analyses. Microchemical chips are expected to make analyses in minutes or even shorter periods in the future. Now, on-chip integration of electrophoresis, mostly for genome technology, is the most popular topic in microchemical process research (Fig. 1a) [10]. Highly sensitive detection methods for extremely small amounts of samples are necessary for microchemical technology in general. In the on- *Lecture presented at the IUPAC Workshop, Impact of Scientific Developments on the Chemical Weapons Convention, Bergen, Norway, 30 June–3 July 2002. Other presentations are published in this issue, pp. 2229–2322. ‡ Corresponding author