Miniaturization separation sciences

Significant progress has been realized in the miniaturization of separation sciences and mass spectrometric detection. Presently, the samples are transferred to highly specialized laboratories for analysis. But in the future it may become feasible to bring mass spectrometry as a portable technique to the bed for diagnostic or therapeutic monitoring. 

Lab-on-a-chip is the miniaturization and integration of the complete set of devices used in separation science. It most important functions involve sample preparation, reactions, separations, and detection on a single chip. This arrangement was called p.-TAS by Manz in 1990 [1]. We call it nanoanalyses as the... 

The discovery of semiconductor integrated circuits by Bardeen, Brattain, Shockley, Kilby, and Noyce was a revolution in the micro and nano worlds. The concept of miniaturization and integration has been exploited in many areas with remarkable achievements in computers and information technology. The utility of microchips was also realized by analytical scientists and has been used in chromatography and capillary electrophoresis. In 1990, Manz et al. [1] used microfluidic devices in separation science. Later on, other scientists also worked with these units for separation and identification of various compounds. A proliferation of papers has been reported since 1990 and today a good number of publications are available in the literature on NLC and NCE. We have searched the literature through analytical and chemical abstracts, Medline, Science Finder, and peer reviewed journals and found a few thousand papers on chips but we selected only those papers related to NLC and NCE techniques. Attempts have been made to record the development of microfluidic devices in separation science. The number of papers published in the last decade (1998-2007) is shown in Fig. 10.1, which clearly indicates rapid development in microfluidic devices as analytical tools. About 30 papers were published in 1998 that number has risen to 400 in... 

As already mentioned, the concepts of integration and miniaturization are not new in separation science, but the tools at our disposal for the realization of such systems have changed dramatically with the advent of micromechanical fabrication methods. The advantages of this technology are best appreciated by a closer look at earlier attempts to construct integrated small volume analysis systems using conventional techniques. 

The first two points represent a general motivation for miniaturization in separation science independent of the actual fabrication technology. The benefit of a reduction of the consumption of sample, reagents, and mobile phase in chemical and biochemical analysis is self-evident and does not need to be discussed further (reduced consumption of precious samples and reagents, reduced amounts of waste, environmental aspects). This advantage is, however, sharply contrasted by its severe implications on the detection side, as discussed elsewhere in this volume in detail. The detection of the separated zones of very small sample volumes critically depends on the availability of highly sensitive detection methods. It is not surprising that extremely sensitive laser-induced-fluorescence (LIF) has been the mostly used detection principle for chip-based separation systems so far. 

One of the current trends in separation science is the development of comprehensive or multidimensional separation systems, in which CE and CE-MS are also achieving relative importance. Chemometric approaches like the ones described in this chapter will surely be of great help for the optimization of these more complicated separation systems. Current trends toward miniaturization in separation science are also well known. Ultrafast separations, extremely low sample requirements, and automation of the arrangement are some of these goals. Chemometrics will surely provide an interesting and challenging approach for the optimization of separation conditions in these miniaturized systems, including microchips for years to come. 

The transposition of capillary electrophoresis (CE) methods from conventional capillaries to channels on planar chip substrates is an emergent separation science that has attracted widespread attention from analysts in many fields. Owing to the miniaturization of the separation format, CE-like separations on a chip typically offer shorter analysis times and lower reagent consumption augmented by the potential for portability of analytical instrumentation. Microchip (p-chip) electrophoresis substrates boast optically flat surfaces, short diffusion distances, low Reynolds numbers, and high surface (or interface)-to-volume ratios. By exploiting these physical advantages of the chip over conventional capillaries, efficient p-chip electrophoresis systems can accomplish multiple complicated tasks that may not be realized by a conventional CE system alone. 

The analytical capabilities of miniaturized separation techniques, such as capillary liquid chromatography (LC), nano-LC, and CE, are of interest in some fields of application, but these techniques have not yet reached the food industry, in particular for the determination of acetic acid and its salts. Thus, analytical chemists need to direct their attention toward these trends with the aim of narrowing the gap between science and the food industry. 

The replacement of microcolumns by capillaries has led to the development of very interesting modem alternatives in analytical separation science. Thus, capillary liquid chromatographies (CLC), through so-called micro and nano-HPLC, and capillary electrophoresis (CE), have introduced a true revolution in instmmental separation techniques. However, despite the clear improvement and possibilities these modes represent, miniaturization of the equipment as a whole is not tmly evident. Miniaturization affects many of the components and devices integrated in the commercialized equipment, but the equipment itself is not considered miniaturized at all. The tme pass to miniaturization is given when chromatographic or electrophoretic separations are carried out on chips. 

One of the most topical ways of approaching this type of system, where separation and detection take place sequentially in space and time, to current trends in Science and Technology (e.g. automation and miniaturization) involves integrating both steps. Integrated systems of this type meet the requirements of chemical sensors [7,8] and differ clearly from conventional flow systems, where detection and mass transfer take place at different locations in the continuous configuration. In fact, the characteristic mass transfer of separation techniques takes place simultaneously with detection... 

Multifunctional and adaptive membranes, and miniaturized and integrated separative devices are current trends in membrane science research and development. Increasing societal requests in terms of environmental protection, health, energy savings, etc., are long-term driving forces for such activities. 

The assertions that science and engineering of the 21st century will acquire a nano and angstrom character have proved to be a reality. The limits of miniaturization of separate elements (e.g., density of arranging crystals in microelectronics)... 

To date, HPLC has become the dominating chromatographic technique, with capillary GC being second only to it (for the more volatile analytes). Both GC and H PLC are mature separation techniques today however, HPLC is stiH being developed toward faster and more efficient separations and also partially toward miniaturized columns, particularly for applications in the life science area. The majority of the other techniques already mentioned are niche techniques today, but still important for a relatively smaller number of users compared to HPLC and GC. Electric potential-driven techniques have an added opportunity for new technolc y on microchips. 

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