Separations on a Chip

PAHs to demonstrate the excellent potential of CEC by resolving in under 10 min in isocratic mode 16 PAHs classified as priority pollutants by the U.S. Environmental Protection Agency. Yan et al. employed laser-induced fluorescence (LIF) for the detection of PAHs [80]. The limits of detection (LOD) for individual PAHs ranged between 1 nM and 10 pM, as the linear response spanned 4 orders of magnitude in concentration. A sample of 16 PAHs was also tested by Ngola et al. [26] on a new hydrophobic monolith (Figure 16, from Ref. 26). The synthetic procedure was readily transferable to the chip format and the first CEC separations on a chip were reported [26,81] (Figure 17). 

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. 

Fig. 3 Open tubular capillary electrochromatography separation on a chip of TRITC-labeled tryptic peptides of P-casein. Source From Two-dimensional electrochromatography/capil-lary electrophoresis on a microchip, in Anal. Chem. ...

Figure 1.17 Example of slug-flow generation back into the original liquid phases using a and liquid phase separation on a chip fabricated phase separator that comprises numerous very from polytetrafluoroethylene (capped with light- narrow but high-aspect-ratio ducts at the outlet, transmissive perfluoroalkoxy). Here, chloroform Water phase is colored, whereas the chloroform (organic phase) and water form the segmented is colorless, flow stream, which is subsequently separated...

Chemielabor auf dem Mikrochip, Blick durch die Wirtschafi, May 1997 Lab-on-a-chip protein separation DuPont s investigations general advantages of pTAS DARPA foundation of military biological sensor development MEMS components [223]. 

Co (I I) complex formation is the essential part of copper wet analysis. The latter involves several chemical unit operations. In a concrete example, eight such operations were combined - two-phase formation, mixing, chelating reaction, solvent extraction, phase separation, three-phase formation, decomposition of co-existing metal chelates and removal of these chelates and reagents [28]. Accordingly, Co (I I) complex formation serves as a test reaction to perform multiple unit operations on one chip, i.e. as a chemical investigation to validate the Lab-on-a-Chip concept. 

The range of applications of CE-MS is still rather limited [899]. Few real unknown samples have been analysed by CE-MS. In particular, CE-MS activities for synthetic polymer additive analysis purposes are not abundant. On the other hand, ITP and ITP-CE separations of food additives on a chip have been reported [900]. 

For new analytical techniques to prosper, they must have demonstrated applications to real-world samples, with outstanding figures of merit relative to competing approaches. Table 10.24 opposes the prospects of conventional separation procedures and advanced in situ analyses by the currently most qualifying techniques. Lab-on-a-chip (LOC) devices are unlikely to be robust enough to cope with the moderately complex (i.e. dirty ) matrices that are real-life samples. Industrial chemists need to avoid a lot of work for every analyte and every matrix. Obstacles to solid analysis are relatively poor sensitivities, narrow linear dynamic ranges and unavailability of solid standards. The trend... 

The main bottleneck in the further development of CEC is related with the state of the art of the column manufacturing processes and the robustness of the columns/instrumentation. Moreover, evidence to demonstrate reproducibility of separations from column to column still has to be established. The formation of bubbles in the capillaries due to the Joule heating and variations in EOF velocity on passing from the stationary phase through the frit and into the open tube is still very challenging in packed column CEC. A way to overcome this problem is to use monolithic columns or apply open tubular CEC [108]. Currently, many efforts are placed in improving column technology and in the development of chip-CEC [115] as an attractive option for lab-on-a-chip separations. 

Manz, A., Harrison, D. J., Verpoorte, E. M. J., Fettinger, J. C., Paulus, A., Luedi, H., and Widmer, H. M. (1992). Planar chips technology for miniaturization and integration of separation techniques into monitoring systems. Capillary electrophoresis on a chip.. Chromatogr. 593, 253-258. 

Research has been done showing that rapid pressnre-driven LC analysis can be done with little solvent consumption, demonstrating this as a viable process analytical tool. Using electrokinetic nanoflow pumps LC can be miniaturized to the point of being a sensor system. Developments in terms of sampling to enable sampling directly from a process stream, to the separation channel on a chip are critical for the application of miniaturized process LC. The components (valves and pumps) required for hydrodynamic flow systems appear to be a current limitation to the fnll miniatnrization of LC separations. Detection systems have also evolved with electrochemical detection and refractive index detection systems providing increased sensitivity in miniaturized systems when compared to standard UV-vis detection or fluorescence, which may require precolumn derivatization. 

Lab-on-a-chip separations are reliant upon the pumping of solutions by electroosmosis and the separation of charged ions in an electric field by electrophoresis. Each ion has an electrophoretic mobility, which is proportional to its charge and inversely proportional to the frictional forces that act upon it [13]. The velocity at which an ion migrates in the electric field is dictated by its size, charge, and the applied potential, as seen in Eq. (13.1), where v is the velocity of the ion, /xg is the electrophoretic mobility, E is the applied potential, q is the charge of the ion, q is the viscosity of the solution, and r is the radius of the ion ... 

Unlike capillary electrophoresis, wherein absorbance detection is probably the most commonly utilized technique, absorbance detection on lab-on-a-chip devices has seen only a handful of applications. This can be attributed to the extremely small microchannel depths evident on microchip devices, which are typically on the order of 10 pm. These extremely small channel depths result in absorbance pathlengths that seriously limit the sensitivity of absorbance-based techniques. The Collins group has shown, however, that by capitalizing on low conductivity non-aqueous buffer systems, microchannel depths can be increased to as much as 100 pm without seeing detrimental Joule heating effects that would otherwise compromise separation efficiencies in such a large cross-sectional microchannel [38],... 

The advent of microfabrication greatly improved pHPLC design and will eventually provide the ultimate lab-on-a-chip. Shintani et al. built a multichanneled pHPLC for the separation of... 

Clever variations of electrophoresis allow us to separate neutral molecules as well as ions, to separate optical isomers, and to lower detection limits by up to 106. Adaptations of electrophoresis provide a foundation for new technology called analysis on a chip. In the future, drug discovery and clinical diagnosis will depend on small chips carrying out unprecedented numbers of operations with unprecedented speed. 

S. Ferko, V. A. VanderNoot, J. A. A. West, R. Crocker, B. Wiedenman, D. Yee, and J. A. Fruetel, Hand-Held Microanalytical Instrument for Chip-Based Electrophoretic Separations of Proteins, Anal. Chem. 2005, 77, 435 J. G. E. Gardeniers and A. van den Berg, Lab-on-a-Chip Systems for Biomedical and Environmental Monitoring, Anal. Bioanal. Chem 2004,378, 1700 J. C. McDonald and G. M. Whitesides, Poly(dimethylsiloxane) as a Material for Fabricating Microfluidic Devices, Acc. Chem. Res. 2002,35, 491 Y. Huang,... 

S. Joo, M. Duhon, M. Heller, B. Wallace, and X. Xu, Dielectrophoretic Cell Separation and Gene Expression Profiling on Microelectronic Chip Arrays, Anal. Chem 2002, 74, 3362 D. Figeys and D. Pinto, Lab-on-a-Chip A Revolution in Biological and Medical Sciences, Anal. Chem 2000, 72, 330A C. H. Legge, Chemistry Under the Microscope—Lab-on-a-Chip Technologies, ... 

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