Microchip systems

FIGURE 6-22 Schematic of a microchip system for enzymatic assays. Hie channels terminate at reservoirs containing the indicated solutions. (Reproduced with permission from reference 81.)... 

An electrochemical detector uses the electrochemical properties of target analytes for their determination in a flowing stream. Electrochemistry (EC) offers great promise for microchip systems, with features that include high sensitivity (approaching that of fluorescence), inherent miniaturization and integration... 

Figure 13.6 Schematic diagram of the dual-end injection CE microchip system with the movable conductivity detector for simultaneous measurements of explosive-related anions and cations, (a) injection mode and (b) separation mode. (a,e) Running buffer reservoirs, (b,d) unused reservoirs, (c, f) sample reservoirs, (g) injected cation plug, (h) injected anion plug, (i) movable contactless conductivity detector, (j—1) cations 1-3, (m-o) anions 1-3. (Reprinted in part with permission from [33]. Copyright 2003 Wiley Interscience.)...

EC detectors have already proven to be well suited for CE microchip systems, and therefore as commented in a recent review of EC detection for capillary electrophoresis microchips by Wang [48], the rapid progress of EC detection for CE microchips over the past six years suggests the major impact it may have in the near future . Other revisions on developments in EC detection for microchip capillary electrophoresis can be found in Refs. [49-51]. 

Liu, B.E, Ozaki, M., Terabe, S., Utsumi, Y., Hattori, T., Comparison of different strategies of chemiluminescence detection for microchip system fabricated in poly(Dimethylsiloxane). Micro Total Analysis Systems Proceedings pTAS 2002 symposium, 6th, Nara, Japan, Nov. 3-7, 2002, 293-295. 

Chiem NH, Harrison DJ. Microchip systems for immunoassay an integrated im-munoreactor with electrophoretic separation for serum theophylline determination. Clin Chem 1998 44 591-598. 

C. Spegel, A. Heiskanen, S. Pedersen, J. Enmeus, T. Ruzgas and R. Taboryski, Fully automated microchip system for the detection of quantal exocytosis from single and small ensembles of cells, Lab on a Chip, 8(2), 323-329 (2008). 

In another study, Gao and coworkers [124] developed an integrated microchip system for rapid and sensitive protein identification generated by on-line protein... 

Antibodies, enzymes, and other reagents used for immunoassay are expensive, hence, when used in the conventional method causes a large problem. Moreover, in many cases, samples are very precious or only a very small amount of samples can be obtained. Therefore, any reduction of the consumption in the microchip systems is welcomed. 

The Kitamori group has pioneered the use of TLM in microchip systems, where both an excitation and a probe beam are focused into a liquid sample—an example of its utility is provided with immunoassay in Chapter 34. The energy of the excitation beam is absorbed by the sample species and results in a localized temperature increase that affects the refractive index (RI) within the medium. The probe beam, which is selected such that there is no absorption, is subject to the thermal lens... 

While the vast majority of microdialysis sampling to date has been achieved in conjunction with conventional systems, microdialysis has also been coupled online with biosensors and, more recently, to microchip-based separation devices. These devices can be fabricated using low cost materials and are amenable to mass production [11]. The smaller dimensions of microchip systems minimize sample and reagent volume requirements and allow placement of the analysis system closer to the aqueous sample or animal being sampled. Due to the planar nature of microchip devices, additional sample handling procedures such as preconcentration, mixing, extraction, or derivatization can also be carried out on the same platform [12-15]. Considerations for coupling microdialysis to microchip instrumentation systems will be discussed in Section 48.5. 

If a single analyte is to be detected, a simple flow-through microdialysis/microchip system may suffice. If multianalyte determination is needed, a separation-based microchip device can allow resolution and detection of several analytes in a single sample (Section 48.5.4). In flow-through devices, the perfusate is directed to an array of sensors, which may be also be modified to allow detection of different analytes and improve detection sensitivity. 

There have only been a few reports of coupling microdialysis to microchip-based separation systems. Ideally, the microchip system should allow the injection of discrete sample plugs from a continuously flowing stream of dialysate without disturbing the separation element of the analysis. This allows maximal temporal resolution and limits the effect of perfusion flow rate on system performance. 

Future developments will see the optimization of device design and the investigation of alternative materials for microchip, electrode, and membrane fabrication. It is envisioned that further advances in fabrication and integration procedures will allow the development of implantable/wearable micro-dialysis/microchip systems for personal or on-animal monitoring. Integration of the separation-based systems with powerful detection techniques such as MS will further improve the detection capability of these systems for biological, pharmaceutical, and environmental monitoring. 

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