Microchip fabrication, design

Now for some practical examples of how phase diagrams are used. In the first, a typical design problem, we find out how solders are chosen for different uses. In the second we look at the high-technology area of microchip fabrication and study the production, by zone refining, of ultra-pure silicon. And lastly, for some light-hearted relief, we find out how bubble-free ice is made for up-market cocktails. 

Microchips fabrication with integrated tips can result in improved spray repeatability and efficiency since alignment and dead volume are not a critical issue anymore. However, production of fine and robust nanospray emitters as an integral part of a microdevice is not trivial, and highly specialized microfabrication procedures are required. Microfluidic devices with integrated ESI tips have been produced for infusion experiments, but to date, no microchips with such a design was fabricated for CE separation prior to MS detection. 

From the perspective of the clinical laboratory, miniaturization has been a long-term trend in clinical diagnostics instrumentation. For example, capillary electrophoresis instruments (see Chapter 5) and mass spectrometers have been implemented on microchips of silicon, glass, or plastic. In actuality, however, these devices are not manufactured on a nanometer scale but rather on a micrometer scale. Consequently, this chapter will be concerned with microminiaturized devices whose key components (1) are approximately 100 micrometers in size, (2) are employed in analytical measurement, and (3) require special forms of fabrication designed for microdevices. Although this chapter does not attempt to discuss submicron or molecular structures at the nanometer scale, it should be noted that applications discussed later in it require only nanoliter (nL) quantities of a sample or deal with individual cells that may have cell volume in the picoHter (pL) to nL range. 

While one of the limitations of LIF detection is that few target molecules exhibit native fluorescence, especially biologically relevant proteins and DNA of clinical interest, several different labeling approaches both on- and off-chip have been demonstrated. For the former, the microchip fabrication steps provide the ability to incorporate additional structures into the design, in many cases without adding more steps (or cost) to the fabrication process. Examples include the additional channels and reaction chambers used to perform both precolumn" and postcolumn" labeling of amino acids. 

The present chapter will review instrumental aspects for successful coupling of CE with MS, regarding interfaces, ionization sources, and analyzers. Practical considerations concerning different CE modes such as CZE, NACE, MEKC, and CEC coupled with MS will also be discussed and illustrated with a focus on recent pharmaceutical applications. Additionally, quantitative CE-MS will be presented and various methodologies used to achieve sensitive and repeatable analysis will be discussed. Finally, the final section of this chapter will give an overview on new devices (i.e., microchips), hyphenated to MS, in terms of fabrication methods, microchip designs, MS interfacing, and applications. 

In order to further investigate and understand the unfavorable results regarding sample elution time of the weir-SMEC as compared to the grid-SMEC, microfluidic modeling of the flow profile immediately after the weir was performed. When the size of fluidic channels is in the dimensions of a few hundred micrometers or smaller and aqueous-based solutions are used, it is well known that pressure-driven fluid transport is usually heavily dominated by laminar flow. Therefore microfluidic modeling can be employed to investigate and study fluid flow characteristics in microchip designs prior to fabrication. 

This chapter reviews the current state of the art in the design and fabrication aspects of microfabricated electrophoresis devices, as well as the development of popular detection modes applicable to microchip devices. Potential applications in the pharmaceutical industry are highlighted based on the successful analysis of proteins, peptides, DNA, chiral separations, and some small molecules. 

Microchip electrophoresis is a natural extension of CE, with the capillary replaced by a channel etched into a substrate and then covered with a cover plate to enclose the channel. The components necessary to carry out the electrophoresis including electrodes, buffer reservoirs, and sample reservoirs must be fabricated into the chip itself or designed into an interface that allows the macroscopic world access to the microscopic structures. The design, fabrication, and substrate materials of microchips are the important factors in determining what components can be fabricated into the device itself and what must be included in an interface as well as in determining what types of analyses can be carried out on a given device. 

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