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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

Team

Principal Investigator

Ryan Kelly
Institution
Brigham Young University

Team Members

Robert Dixon
Institution
Pacific Northwest National Laboratory

Nitin Agrawal
Institution
George Mason University

Xuefei Sun
Institution
Pacific Northwest National Laboratory

Richard Smith
Institution
Pacific Northwest National Laboratory

Keqi Tang
Institution
Pacific Northwest National Laboratory

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