Coupling Microfluidic Devices to Mass

Coupling microfluidic devices to mass spectrometers Interfacing Lab-on-a-Chip platforms with mass spectrometers using MALDl and ESI... 

ESI and MALDI are considered to be the most appropriate candidates for coupling microfluidic devices to mass spectrometry. In what follows, a survey of the different kinds of microfluidic-MS interfaces reported in the literature is presented, and the most promising geometries are discussed. 

Two factors favor the use of nanoelectrospray ionization for coupling microfluidic devices to mass spectrometers. The first is the similarity between the conventional puUed-glass capillary tips and the nanospray nozzles developed for microdevices discussed above the second springs from the linear geometry of microfluidic channels. Thus, nanospray ionization techniques are probably the most likely to be used for the construction of robust interfaces between... 

The coupling of microfabricated devices to mass spectrometers has been a great success through the efforts of many laboratories around the world. The depth of applications has been limited by our ability to perform protein chemistry and biochemistry on a scale compatible with microfluidic devices. To date, microfluidic devices have been generally used to handle small amounts of sample. The next frontier for this field of research will be the development and integration of in situ chemical and biochemical processing. 

Recently, we described the first example of the coupling of a microfluidics device to a MALDI-TOF mass spectrometer, by integrating an on-chip microreaction unit with a MALDI-TOF standard sample plate.27 This allows (bio)chemical reactions to take place in the MALDI-TOF instrument. Since it is based on a pressure-driven fluidics handling method, using the vacuum in the ionization chamber of the MALDI-TOF-MS system, this approach avoids wires and tubes for feed and flow control. 

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. 

Mostly, mass spectrometers have been used widely for nanodetection in NLC and NCE due to its low detection limits and ease of hyphenation with microfluidic devices. However, attempts have been made to couple other detectors with NLC and NCE. The state of the art of hyphenation of detectors in NLC and NCE is still in its development stage. More advances are expected in the near future for detection at extremely low concentrations for a wide range of molecules. 

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... 

Ramsey and Ramseyalso described microchip interfacing to an ion trap mass spectrometer. Microfluidic delivery was realized by electroosmotically induced pressures and electrostatic spray at the channel terminus was achieved by applying a potential between the microchip and a conductor spaced 3-5 mm from the channel terminus. Tetrabutylammonium iodide was tested as a model compound with this device. Later, Ramsey et reported use of a microchip nanoelectrospray tip coupled to a time-of-flight mass spectrometer for subattomole sensitivity detection of peptides and proteins. A fluid delivery rate of 20-30 nL/min was readily obtained by applying an electrospray voltage to the microchip and the nanospray capillary attached at the end of the microfabricated channel without any pressure assistance. 

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