Chip-based Analytical Instruments

What does the future hold for CEC It is impossible to predict the path the technique will follow. It is of course unlikely that it will ever enjoy the great breadth of application of HPLC and GC. That said, it is entirely possible that the technique will find one or more niches in which it will thrive. Likely areas of application include field-portable, low-cost, chip-based analytical instruments disposable components in medical diagnostic/assay devices and consumables for clinical diagnostic tools. 

Electrochemical detection offers also great promise for CZE microchips, and for other chip-based analytical microsystems (e.g., Lab-on-a-Chip) discussed in Section 6.3 (77-83). Particularly attractive for such microfluidic devices are the high sensitivity of electrochemical detection, its inherent miniaturization of both the detector and control instrumentation, low cost, low power demands, and compatibility with micromachining technologies. Various detector configurations, based on different capillary/working-electrode... 

Recent breakthroughs in miniaturized analytical instrumentation include fully integrated lab-on-a-chip and micro total analysis systems. The former have had only moderate success as many analytical chemists have been reluctant to accept them [67]. At present, chip-based analytical systems are subject to major shortcomings such as the risk of analyte adsorption on walls and at interfaces — which is important especially in low-volume analytical systems — and optical interference at the walls of the chips hampering detection. Further research in this field is required in order to effectively circumvent these shortcomings [68]. 

LIF detection is the most sensitive optical method so far, but is hard to miniaturize in order to satisfy the ultimate goal of a microfluidic chip that assembles all analytical processes within one micrometerscale microstructure. Therefore, how to achieve the miniaturization of fluorescence detection on microdevices is becoming an active field for lab-on-a-chip research. Several examples demonstrate recent advances in miniaturized LIF detection on the microchip. In 2005, Renzi et al. designed a hand-held microchip-based analytical instrument that combines fluidic, optics, electrical power, and interface modules and integrates the functions of fluidics, microseparation, lasers, power supplies etc., into an... 

As in the SLM systems, FS- and HF-MMLLE configurations can be run automatically in flowing modes and operated off-line or connected on-line to analytical instruments. Recently, a microfluidic chip-based FS-MMLLE system was reported.83 In addition, miniaturized, nonautomated, nonflowing, off-line MMLLE systems are usually used with HF membranes. The emphasis in this section will be placed on these latter modes of MMLLE operation. 

The so-called micro-total analytical systems (/tTAS) can integrate sample handling, separation, and detection on a single chip [9]. Postcapillary reaction detectors can be incorporated as well [10]. Fluorescence detection is the most common method employed for these chip-based systems. A commercial instrument (Agilent 2100 Bioanalyzer) is available for DNA and RNA separations on disposable chips using a diode laser for LIF detection. In research laboratories, polymerase chain reaction (PCR) has been integrated into a chip that provides size separation and LIF detection [11]. 

Several companies are developing analytical instruments and information systems based on the concept of lab-on-a-chip technology (458-463). The chip-... 

Initially the main reason for miniaturising separations was to enhance analytical performance and the combination of integration of components and small size were seen as advantages. These chip devices are based mainly on chromatography though electrophoretic separations play an increasing part. As the years go by, these on-chip separation devices have become more and more important as analytical instrumentation tools. 

Section IV then tackles the most recent trend in analytical instrumentation, which is miniaturisation and the drive to create lab-on-a-chip devices. In this section, 1 discuss the development of chip-based technologies and the challenges associated with this such as pumping fluids on the microscale, fitting components onto a chip, detection strategies and how processes such as mixing are so different in the microworld when compared to the macroworld. 

Capillary electrochromatography has experienced rapid progress during the last decade, expanding from 17 publications in 1994 to 191 in 2007. This has also led to several books and reviews [93-104] and analytical instrumentation is readily commercially available [105]. The developments in CEC include research on optimum stationary phases (polymer or silica based, adsorbed or imprinted, etc.), mobile phases (aqueous electrolytes with/without admixture of organic solvents or pseudophases) and apparatus design (open-tubular, packed or monolithic capillaries) up to lab-on-a-chip devices for pTAS [107]. 

Another instrumental development is based on the fact that the generation of smaller droplets is more favorable in terms of droplet evaporation during ESI, of sensitivity and the abihty to preserve non-covalent molecular associates. Thus, nanoelectrospray ionization (nESI) has been developed [68], where the analyte is sprayed from a gold-coated fused-silica capillary with a tip diameter of 1-5 pm rather than from capillaries with a 100-150-pm tips that are used in conventional (pneumatically assisted) ESI. In nESI, flow-rates as low as 20 nl/min can be nebulized. Thus, gentler operating conditions (temperature, gas flows, needle voltage) can be achieved. In order to more readily implement nESI in LC-MS operation, integrated chip-based nano-LC-nESI devices have also been developed [69]. 

The current trend in analytical chemistry applied to evaluate food quality and safety leans toward user-friendly miniaturized instruments and laboratory-on-a-chip applications. The techniques applied to direct screening of colorants in a food matrix include chemical microscopy, a spatial representation of chemical information from complex aggregates inside tissue matrices, biosensor-based screening, and molec-ularly imprinted polymer-based methods that serve as chemical alternatives to the use of immunosensors. 

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