ABSTRACT
Microfabrication has played a central role in the development and current mass production of microprocessors and other semiconductor chips for the computer industry. This miniaturization process has brought down the scale of computers from a machine that typically occupied several rooms to the size of a small notebook. Today these microfabrication processes and other newly developed techniques are being explored for fabricating silicon, glass, or plastic chips with diverse analytical functions for use in basic research, forensic science, and clinical diagnostics. These devices are showing great promise in facilitating the total integration of three classic tasks involved in any bioassay: (1) sample processing, (2) biochemical reaction, and (3) detecting the result, and therefore form the basis of smaller, more efficient bench-top or even palm-top analyzers. Any system with these characteristics has been termed a Micro-Total Analytical System (µ-TAS) (Manz et al., 1990) or a Laboratory-on-a-Chip (Colyer et al., 1997). Rapid progress has been made in developing laboratory-on-a-chip systems in recent years. Sample processing is the first stage of a lab-on-a-chip analysis. It generally implies the ability to process crude biological samples (e.g., blood, urine, effluent) in order to isolate target molecules or bioparticles of interest such as nucleic acids, proteins, or cells. The biochemical reaction may include various types of chemical or enzymatic reactions such as chemical labeling, DNA amplification using PCR (polymerase chain reaction), or strand displacement amplification (SDA) or DNA restriction enzyme digestion. Detection of the result can be achieved by one of the established detection techniques (e.g., optical detection, electrochemical detection). The integration of the three steps described above cannot be achieved without the use of microfabricated devices and microfluidic control units (e.g., miniaturized valves and pumps). Partial integration of these three key steps has included the integration of sample preparation with the biochemical reaction (Wilding et al., 1998; Cheng et al., 1998c; Li and Harrison, 1997) and the integration of the biochemical reaction with molecular detection (Jacobson and Ramsey, 1996; Woolley et al., 1996; Waters et al., 1998a,b; Burns et al., 1998). In a recent report, a complete labon-a-chip system has been constructed that clearly demonstrates the possibility of this type of work (Cheng et al., 1999). Compared to traditional approaches, a fully integrated portable lab-on-a-chip system has the advantages of reduced contamination, minimal human intervention, portability, reproducibility, and low consumption of costly reagents and samples.
