Chip-based Instrumentation

Chip-based microdevices are finally discussed, regarding fabrication methods, designs, MS interfacing, and applications. Current capabilities and limitations for future use are emphasized considering improvements in methodology and instrumentation. 

Either the information obtained during the data-dependent acquisition is sufficient or a fraction of interest can be re-analyzed by chip-based infusion at a flow rate ca. 200 nl min. Due to the miniaturization sample consumption is very low (typically 1-3 pi) and acquisition time is no longer critical. Therefore various MS experiments can be performed on various instruments, including MS and accurate mass measurements. An additional advantage is that the eluent can be removed and the infusion solvent can be optimized for positive or negative ion detection or for deuterium exchange measurements. 

Fig. 5.9 Design of the chip-based enzyme ESI-MS assay. MS instrument Ion-trap mass spectrometer (LCQ Deca, Thermo Electron). I Sample components/inhibitors injected by flow injection or eluting from capillary HPLC column. E Infusion pump delivering the enzyme cathepsin B. S infusion pump delivering the substrate Z-FR-AMC. Micro-chip design Vrije Universiteit Amsterdam. Micro-chip production Micronit Microfluidics BV (Enschede, The Netherlands).

A chip-based nanospray interface between an HPLC and the MS has been introduced by Advion Biosystems (Ithaca, NY). This instrument aligns a specialized pipette tip with a microfabricated nozzle, set in an arrayed pattern on a silicon wafer. The advantage of this interface is that each sample is sprayed through a new nozzle, thus virtually eliminating cross contamination. 

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,... 

The most common types of MS/MS instruments available to researchers in food chemistry include triple quadrupole mass spectrometers and ion traps. Less common but commercially produced tandem mass spectrometers include magnetic sector instruments, Fourier transform ion cyclotron resonance (FTICR) mass spectrometers, and quadrupole time-of-flight (QTOF) hybrid instruments (Table A.3A.1). Beginning in 2001, TOF-TOF tandem mass spectrometers became available from instrument manufacturers. These instruments have the potential to deliver high-resolution tandem mass spectra with high speed and should be compatible with the chip-based chromatography systems now under development. 

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. 

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... 

Separation of simple mixtures [13,44] to more complicated biofluidic mixtures with CE-NMR and CEC-NMR have been reported [51,52], Several instrumental modifications and methodologies have been described to use CE/CEC-NMR as a diagnostic tool [44,53-55], Though still in its infancy, chip-based CE-NMR with microfabricated microcoils may be able to analyze picoliter volume samples [56,57]. 

Ramseier A, von Heeren F, Thormann W. Analysis of fluorescein isothiocyanate derivatized amphetamine and analogs in human urine by capillary electrophoresis in chip-based and fused-silica capillary instrumentation. Electrophoresis 1998 19 2967-2975. 

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]. 

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]. 

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