Chip-MS Interfacing

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. 

C. Wang, R. Oleschuk, F. Ouchen, J. Li, P. Thibault, D. J. Harrison, Integration of immobilized trypsin bead beds for protein digestion within a microfluidic chip incorporating CE. separations and an ESI-MS interface. Rapid Conunun. Mass Spectrom., 14 (2000) 1377. 

Mass spectrometry (MS) is one of the most powerful detection techniques used in liquid-phase analyses,1 mainly due to the ease of interfacing with separation techniques such as capillary electrophoresis (CE)2,3 and high-performance liquid chromatography (HPLC).4 Due to its sensitivity and applicability to a wide variety of chemical and biochemical species, MS is also used for the analysis of (bio)chemical molecules processed in microfluidics devices.5,6 Electrospray ionization (ESI)7 10 is often used to transfer samples from microfluidics chips to a mass spectrometer, involving analyte ionization directly from solutions and operating at flow rates typically used in microfluidics devices.11 Due to its effectiveness, the use of chip-MS coupling has rapidly spread in many research areas with bioanalytical applications,12 such as the... 

Commercially, Agilent Technologies produces chips for both direct infusion into a mass spectrometer and for HPLC-MS applications. The chips accommodate nanoflow rates with an electrospray ionisation source, are about the size of a credit card and are rensable. The infusion chip is for collecting direct MS or tandem MS data. The protein HPLC chip has both a sample enrichment and CIS separation column on the chip, as well as the connections and spray nozzles for electrospray. There are also a small molecule chip and a glycan chip. The chip being used is placed in a Chip Cube MS interface which positions the sprayer tip perpendicular to the MS inlet (Figure 10.7). 

FIGURE 53.3 A microchip-MS interface with a nebulizer that includes an aerodynamic focusing chamber for directing the ESI plume into the mass spectrometer sampling orifice. (Reprinted from Grym, J., et ah. Lab Chip, 6, 1306-1314, 2006. Copyright 2006. With permission from The Royal Society of Chemistry.)... 

Alternatively, Foret et al. - have devised a microfabricated device that incorporated a sample injection loop, a separation channel for CE, lEF, or chromatography, and a liquid junction MS interface. The samples were loaded sequentially from a microtiter plate with the aid of an electropneumatic distributor, and microfluidic manipulations on the chip were accomplished with electrokinetic and pressure fluidic control. The sequential CE-ESI-MS analysis of protein tryptic digests is shown in Figure 53.25. 

FIGURE 53.26 Microfluidic chip interfaced to an antosampler and to an ESI-TOF-MS detection system, (a) Schematic diagram of the total system. The chip comprises an enzyme microreactor/preconcentrator, a CE separation channel, and a capillary nanoESI-MS interface, (b) Tandem mass spectra of 2D-gel-isolated proteins from Neisseria meningitidis. (Reprinted from Li, J., et al., Pwteomics, 1,975-986,2001. Copyright 2001. With... 

Brivio, M., Oosterbroeck, R.E., Verboom, W., van den Berg, A., Reinhoudt, D.N., Simple chip-based interfaces for on-line monitoring of supramolecular interactions by nano-ESl MS, Lab Chip, 5, 1111-1122, 2005. 

Razunguzwa TT, Lorke J, Timperman AT (2005) An electrokinetic/hydtodynamic flow microfluidic CE-ESI-MS interface utilizing a hydrodynamic flow restiiclOT for delivery of samples under low EOF conditions. Lab Chip 5(8) 851—855... 

FIGURE 6 Schematic representation of different interfaces for chip CE-ESI/MS (A) spray directly from the chip, (B) liquid-junction capillary interface, (C) gold-coated capillary interface, and (D) coaxial sheath-flow configuration. Reprinted from reference 410 with permission from Elsevier Science B.V. 

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