Recent progress in the development of mTAS for clinical analysis

A recent goal in the development of analytical techniques has focused on the integration of sample collection, sample preparation, and analysis steps on a single integrated platform referred to as either Lab-on-a-Chip (LOC) or miniaturized total analysis systems (mTAS). Sample preparation steps can include filtration, derivatization, and extraction among others. Analysis methods include separations by chromatography or electrophoresis, and direct or indirect detection using spectroscopy or electrochemistry. The well-developed photolithographic patterning techniques and the planar substrates allow easy system miniaturization. Miniaturization and integration of such a system has the potential to shrink a room full of instruments into a single compact LOC device. One of the most exciting areas of application for this new technology is clinical analysis. The ability to create inexpensive point-of-care monitoring devices for complex analysis conditions has attracted much attention to this new and exciting field. The conceptual expression of LOC technology was demonstrated as early as the 1970’s in the development of miniaturized gas chromatography columns which also incorporated an injector and a detector1 and developed by Manz et al. in modern form who first suggested the idea of the microfabricated analysis system.2,3 Later, Manz et al. also demonstrated microfabricated capillary electrophoresis systems.4–6 The demonstration and subsequent explosion of research in LOC devices was the result of improvements in both microfabrication techniques and separation techniques. The development of capillary electrophoresis (CE) by Jorgenson and Lukacs was one key as it provides a reliable method for chemical separation and fluidic transport that does not require external mechanical pumps.7,8 LOC technology has numerous advantages over traditional systems based on robotics and conventional analysis instrumentation. First, mature microfabrication techniques adapted from the semiconductor industry allow mass production of LOC devices reducing the cost per device and allowing massively parallel systems to be constructed easily.9 Second, the devices follow scaling rules that result in a decrease in sample and reagent consumption plus an increase in analytical performance,2 which also reduces the overall cost of the analysis as the sizes decrease. The low-scale also allows a multianalyte analysis to be performed from a finger prick of blood as opposed to the large volumes required for standard techniques.10,11 Third, the rapid prototyping techniques used to fabricate microchips allow the possibility of going from a concept to a working device in hours.12 Finally, the small size of the LOC system will ultimately lead to the development of portable analysis devices for point-of-care diagnostics and environmental monitoring.