Miniaturization microchips

Over the past decade, Raman spectroscopy has continued to develop as a prime candidate for the next generation of in situ planetary instruments, as it provides definitive stmctural and compositional information of minerals in their natural geological context. A time resolved Raman spectrometer have been developed that uses a streak camera and pulsed miniature microchip laser to provide picosecond time resolution (Blacksberg et al. 2010). The ability to observe the complete time evolution of Raman and fluorescence spectra in minerals makes this technique ideal for exploration of diverse planetary environments, some of which are expected to contain strong, if not overwhelming, fluorescence signatures. In particular, it was found that conventional Raman spectra from fine grained clays. 

Electroosmotic flow (EOE) is thus the mechanism by which liquids are moved from one end of the sepai ation capillai y to the other, obviating the need for mechanical pumps and valves. This makes this technique very amenable to miniaturization, as it is fai simpler to make an electrical contact to a chip via a wire immersed in a reservoir than to make a robust connection to a pump. More important, however, is that all the basic fluidic manipulations that a chemist requires for microchip electrophoresis, or any other liquid handling for that matter, have been adapted to electrokinetic microfluidic chips. 

Electronic devices that operate using the spin of the electron and not just its electric charge are on the way to becoming a multibillion-dollar industry—and may lead to quantum microchips (4). As progress in the miniaturization of semiconductor electronic devices leads toward chip features smaller than lOOnm in size, device engineers and physicists are inevitably faced with the fast-approaching presence of quantum mechanics—that counterintuitive, and to some mysterious, realm of physics wherein wavelike properties control the behavior of electrons. 

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... 

Several successful attempts were done to transfer classical CEIA to a microchip-based format. This kind of miniaturization is a trend that can overcome the limitations of CE in high-throughput systems. On-chip CE offers both parallel analysis of samples and short separation times. Koutny et al. showed the use of an immunoassay on-chip (32). In this competitive approach fluorescein-labeled cortisol was used to detect unlabeled cortisol spiked to serum (Fig. 8). The system showed good reproducibility and robustness even in this problematic kind of sample matrix. Using serum cortisol standards calibration and quantification is possible in a working range of clinical interest. This example demonstrated that microchip electrophoretic systems are analytical devices suitable for immunological assays that can compete with common techniques. 

Nevertheless, the major issue in the miniaturization of this kind of assays continues to be the strong non-selective interactions with the polymers. This problem is often avoided, or at least minimized, on large scale experiments such as chromatographic separations. However, it is not easy to solve in the case of microsensors or microchips and direct or indirect assays, where competition can be strongly affected by unspecific binding. 

Amperometric detection is the preferred method for the analysis of nitroaromatic explosives on microchip devices since it offers up to three orders of magnitude higher sensitivity than indirect LIF and it has a great potential for miniaturization and integration on microchip platform. Presence of nitrogroup allows its cathodic reduction to form al-kylhydroxyamines. The reduction mechanism of polynitroaromatic compounds is complex and depends on the number of nitro groups,... 

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... 

Significant advances have occurred during the past decade to miniaturize the size of the measurement system in order to make online analysis economically feasible and to reduce the time delays that often are present in analyzers. Recently, chemical sensors have been placed on microchips, even those requiring multiple physical, chemical, and biochemical steps (such as electrophoresis) in the analysis. This device has been called lab-on-a-chip. The measurements of chemical composition can be direct or indirect, the latter case referring to applications where some property of the process stream is measured (such as refractive index) and then related to composition of a particular component. 

Miniaturized LC/MS formats based on micromachined chip-based electrospray emitters and ionization sources on silicon (Schultz et al., 2000 Licklider et al., 2000 Ramsey and Ramsey 1997 Xue et al., 1997) and plastic (Vrouwe et al., 2000 Yuan and Shiea, 2001, Tang et al., 2001) microchips is a proactive approach for scale-down platforms. Various micromachining processes are used to fabricate these devices. These microanalytical technologies would create integrated sample preparation and LC/MS applications. The potential benefits of such a system include reduced consumption of sample/reagents, low cost, and disposability. 

Microfluidics and miniaturization hold great promise in terms of sample throughput advantages [100]. Miniaturization of analytical processes into microchip platforms designed for micro total analytical systems (/i-TASs) is a new and rapidly developing field. For SPE, Yu et al. [123] developed a microfabricated analytical microchip device that uses a porous monolith sorbent with two different surface chemistries. The monolithic porous polymer was prepared by in situ photoinitiated polymerization within the channels of the microfluidic device and used for on-chip SPE. The sorbent was prepared to have both hydrophobic and ionizable surface chemistries. Use of the device for sorption and desorption of various analytes was demonstrated [123]. 

A miniaturized high-voltage power supply (powered by batteries) was constructed for portable microchip work [293]. 

Ocvirk, G., Tang, T., Harrison, J.D., Optimization of confocal epifluorescence microscopy for microchip-based miniaturized total analysis systems. Analyst 1998, 123(7), 1429-1434. 

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