Microfluidic electrospray ionization

Some reviews [5-7] have appeared on NCE-electrospray ionization-mass spectrometry (NCE-ESI-MS) discussing various factors responsible for detection. Recently, Zamfir [8] reviewed sheathless interfacing in NCE-ESI-MS in which the authors discussed several issues related to sheathless interfaces. Feustel et al. [9] attempted to couple mass spectrometry with microfluidic devices in 1994. Other developments in mass spectroscopy have been made by different workers. McGruer and Karger [10] successfully interfaced a microchip with an electrospray mass spectrometer and achieved detection limits lower than 6x 10-8 mole for myoglobin. Ramsey and Ramsey [11] developed electrospray from small channels etched on glass planar substrates and tested its successful application in an ion trap mass spectrometer for tetrabutylammonium iodide as model compound. Desai et al. [12] reported an electrospray microdevice with an integrated particle filter on silicon nitride. 

Kim, J.-S., Knapp, D.R., Miniaturized multichannel electrospray ionization emitters on poly(dimethylsiloxane) microfluidic devices. Electrophoresis 2001,22(18), 3993-3999. 

Kameoka, J., Orth, R., Ilic, B., Czaplewski, D., Wachs, T., Craighead, H.G., An electrospray ionization source for integration with microfluidics. Anal. Chem. 

Plastic microdevices for high-throughput screening with MS detection were also prepared for detection of aflatoxins and barbiturates. These devices incorporated concentration techniques interfaced with electrospray ionization MS (ESI-MS) through capillaries [2], The microfluidic device for aflatoxin detection employed an affinity dialysis technique, in which a poly (vinylidene fluoride) (PVDF) membrane was incorporated in the microchip between two channels. Small molecules were dialyzed from the aflatoxin/antibody complexes, which were then analyzed by MS. A similar device was used for concentrating barbiturate/antibody complexes using an affinity ultrafiltration technique. A barbiturate solution was mixed with antibodies and then flowed into the device, where uncomplexed barbiturates were removed by filtration. The antibody complex was then dissociated and electrokinetically mobilized for MS analysis. In each case, the affinity preconcentration improved the sensitivity by at least one to two orders of magnitude over previously reported detection limits. 

Microfabricated Multichannel Electrospray Ionization Emitters on Polydimethylsiloxane (PDMS) Microfluidic Devices... 

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... 

Sung, W.C., Makamba, H., and Chen, S.H., Chip-based microfluidic devices coupled with electrospray ionization-mass spectrometry. Electrophoresis, 26,1783-1791, 2005. 

Electrospray ionization from microfluidic devices can be generated directly from the chip surface, from capillary emitters inserted in the chip, or from microfabricated emitters. Liquid sheath, liquid junction, and nano-ESI sources have been implemented on glass, polymeric, or silicon substrates. 

Sung, W.-C., Huang, S.-Y., Liao, P.-C., Lee, G-B, Li, C.-W., Chen, S.-H., Poly(dimethylsiloxane)-based microfluidic device with electrospray ionization mass spectrometry for protein identification. 

Sainiemi L, Sikanen T, Kostiainen R (2012) Integration of fully microfahricated, three-dimensionally sharp electrospray ionization tips with microfluidic glass chips. Anal Chem 84 8973-8979... 

Baker CA, Roper MG (2012) Online coupling of digital microfluidic devices with mass spectrometry detection using an eductor with electrospray ionization. Anal Chem 84 2955-2960... 

The recent progress in micro/nanofabrication technology as well as microfluidics has spurred efforts to interface chip-based separation devices with electrospray ionization mass spectrometers. As frontiers in the ability to miniaturize the mass analyzers are being extended further, an... 

Okhonin, V. Krylova, SM. Krylov, SJM. Nonequilibrium capillary electrophoresis of equilibrium mixtures, mathematical model. Anal. Chem. 2004, 76 (5), 1507-1512. Mellors, J.S. Gorbounov, V. Ramsey, R.S. Ramsey, J.M. Fully integrated glass microfluidic device for performing high-efficiency capillary electrophoresis and electrospray ionization mass spectrometry. Anal. Chem. 2008, 80 (18), 6881-6887. 

Jin, D.-Q., Zhu, Y, Fang, Q. (2014) Swan Probe A Nanoliter-scale and High-throughput Sampling Interface for Coupling Electrospray Ionization Mass Spectrometry with Microfluidic Droplet Array and Multiwell Plate. Anal. Chem. 86 10796-10803. 

Liuni, R, Rob, T., Wilson, D.J. (2010) A Microfluidic Reactor for Rapid, Low-pressure Proteolysis with On-chip Electrospray Ionization. Rapid Commun. Mass... 

Miniaturized ESI interfaces (nanospray electrospray ionization, nanoESI) match the dimensions of microfluidic chips. On-line couphng of microchips with ESI can be accomplished using different interface geometries blunt end, comer outlet, external capillary, external emitter, or monolithic emitter [27], some of which resemble the nanoESI emitters used in CE-MS (see also Chapter 6). In fact, on-chip capillary channels are often used as CE or LC separation columns, and directly linked with the nanoESI emitters. Atmospheric pressure chemical ionization (APCI) and photoionization (APPI) have also been subject to miniaturization but they have not attracted as much attention when it comes to hyphenation with microchips [28]. This situation may change when the novel nanoAPCI interfaces [29] are perfected, providing the way to transmit and ionize non-polar analytes at low flow rates. 

Mellors, J.S., Jorabchi, K Smith, L.M., Ramsey, J.M. (2010) Integrated Microfluidic Device for Automated Single Cell Analysis Using Electrophoretic Separation and Electrospray Ionization Mass Spectrometry. Anal. Chem. 82 967-973. 

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