Microfabrication of Electrospray Emitter Arrays for Improved Sensitivity in Electrospray Ionization-Mass Spectrometry
EMSL Project ID
20492a
Abstract
Liquid chromatography (LC), combined with mass spectrometry (MS), is an
extremely powerful platform for protein analysis, allowing complex mixtures first separated
by LC to be further resolved and identified by MS. Following an LC separation, analytes
must transition to the gas phase and be ionized, which enables sorting by MS according to
mass-to-charge ratio. Electrospray ionization (ESI) currently provides the most effective
direct coupling of LC with MS, due to its high sensitivity and its ability to ionize large, intact
biomolecules from solution. In ESI, a high voltage applied to an emitter at the end of an LC
column creates charged droplets that eventually desolvate to produce individual ionized
species. ESI is most effective in the “nanospray� regime, where low solution flow rates (e.g.,
<50 nL/min) enable the creation of smaller droplets, thus enhancing desolvation and
improving MS quantitation. Unfortunately, operating LC separations at such low flow rates is
problematic, requiring the use of very small columns that are difficult to prepare and which
have enormous back pressures. We propose to microfabricate ESI emitter arrays that will
direct the flow from larger LC columns operated at higher flow rates (e.g., 2 μL/min) into
multiple, individual emitters, thus combining the efficiency of nanospray with the robustness
of conventional capillary LC. For example, given a LC flow rate of 2 μL/min, each orifice in
an array having 40 emitters will operate at 50 nL/min, and the increased ion production will
provide 1–2 orders of magnitude enhancement in detection sensitivity. The improved
performance will enable more proteins to be identified from LC/MS analyses, increasing the
coverage and utility of this already powerful proteomics platform.
Project Details
Project type
Large-Scale EMSL Research
Start Date
2007-05-31
End Date
2010-09-30
Status
Closed
Released Data Link
Team
Principal Investigator
Team Members
Related Publications
Coupling Microfluidics with Mass Spectrometry for Sample-Limited Bioanalyses by Ryan T Kelly. Pittcon Conference March 2010, Orlando, FL
Kelly, R. T.; Tang, K.; Irimia, D.; Toner, M.; Smith, R.D. Elastomeric Microchip Electrospray Emitter for Stable Cone-Jet Mode Operation in the Nano-Flow Regime Anal. Chem. 2008, 80, 3824-3831.
Kelly, R. T.; Tang, K.; Irimia, D.; Toner, M.; Smith, R.D. Elastomeric Microchip Electrospray Emitter for Stable Cone-Jet Mode Operation in the Nano-Flow Regime Anal. Chem. 2008, in press.
Oral Presentation at the CMOS Emerging Technologies conference in Whistler, BC, May, 2010
Sun X, RT Kelly, K Tang, and RD Smith. 2010. "Ultrasensitive Nanoelectrospray Ionization-Mass Spectrometry using Poly(dimethylsiloxane) Microchips with Monolithically Integrated Emitters." Analyst 135(9):2296-2302. Available on the Web: DOI 10.1039/c0an00253d
Sun X, RT Kelly, K Tang, and RD Smith. 2011. "Membrane-Based Emitter for Coupling Microfluidics with Ultrasensitive Nanoelectrospray Ionization-Mass Spectrometry." Analytical Chemistry 83(4):5797-5803. doi:10.1021/ac200960h
Sun X, RT Kelly, WF Danielson, III, N Agrawal, K Tang, and RD Smith. 2011. "Hydrodynamic injection with pneumatic valving for microchip electrophoresis with total analyte utilization." Electrophoresis 32(13):1610-1618. doi:10.1002/elps.201000522