Subattomole-Sensitivity Microchip Nanoelectrospray Source with Time-of-Flight Mass Spectrometry Detection

Abstract

A microfabricated microfluidic device coupled with a nanospray tip for electrospray ionization of dilute solutions is described. The device has been interfaced with a time-of-flight mass spectrometer and evaluated for sensitive, high-speed detection of peptides and proteins. The electrospray voltage was applied through the microchip to the nanospray capillary that was attached at the end of a microfabricated channel. Fluid delivery rates were 20-30 nL min(-)(1) through the hybridized structure without any pressure assistance. On-line microchip electrophoresis has been demonstrated and the effect of the capillary-chip junction on band broadening examined. Full mass spectra are acquired within 10-20 ms at 50-100 spectra s(-)(1) storage rates. Detection of subattomole levels of sample from a 100 nM solution is demonstrated for infusion experiments.

18 Coupling CE and microchip-based devices with mass spectrometry

“…Thus, Bings et al developed a method to obtain low deadvolume connectors, as small as 0.7 nL. 387 When the spray is generated from a transfer capillary, either a disposable nanospray emitter 388,389 or a fused-silica capillary transfer line can be inserted in the microchip. For the former, the ESI nozzle is usually made with a sharp, tapered capillary end from which the liquid sprays to produce small, well-defined droplets.…”

Chemical cytometry on a picoliter-scale integrated microfluidic chip

“…Although the present work analyzed cells through nonspecific fluorescent labeling of amino acids, any of a myriad of optical probes might be used (29). Alternatively, the device might be mated to a mass spectrometer for analysis (30). This device could be used generally for applications that involve reactions and separations of picoliter volumes of liquids.…”

Microfluidic Chip Coupled with Thermal Desorption Atmospheric Pressure Ionization Mass Spectrometry

“…11) It has been demonstrated that micro uidic chips attached with a capillary emitter can be used to carry out tryptic digestion for complex protein samples online. [12][13][14] Moreover, recent miniaturization devices used in the MS application have been focused on multiplexed MS analysis; for example, hundreds of thousands of micrometer scale compartments can be fabricated for high-throughput DNA analysis. 15) Arrays of microchannels have been used for infusion analysis of a variety of samples in connection with MS. 16) Recent developed atmospheric pressure ionization methods such as desorption electrospray ionization (DESI), 17) direct analysis in real time (DART), 18) electrospray-assisted laser desorption/ionization (ELDI), 19) an atmospheric solid analysis probe (ASAP), 20) laser diode thermal desorption (LDTD), 21) extractive electrospray ionization (EESI), 22) and laser spray 23) provide more options when coupling with micro uidic devices.…”