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Title: Chemically Etched Open Tubular and Monolithic Emitters for Nanoelectrospray Ionization Mass Spectrometry

Abstract

We have developed a new procedure for fabricating fused silica emitters for electrospray ionization-mass spectrometry (ESI-MS) in which the end of a bare fused silica capillary is immersed into aqueous hydrofluoric acid, and water is pumped through the capillary to prevent etching of the interior. Surface tension causes the etchant to climb the capillary exterior, and the etch rate in the resulting meniscus decreases as a function of distance from the bulk solution. Etching continues until the silica touching the hydrofluoric acid reservoir is completely removed, essentially stopping the etch process. The resulting emitters have no internal taper, making them much less prone to clogging compared to e.g. pulled emitters. The high aspect ratios and extremely thin walls at the orifice facilitate very low flow rate operation; stable ESI-MS signals were obtained for model analytes from 5-μm-diameter emitters at a flow rate of 5 nL/min with a high degree of inter-emitter reproducibility. In extensive evaluation, the etched emitters were found to enable approximately four times as many LC-MS analyses of proteomic samples before failing compared with conventional pulled emitters. The fabrication procedure was also employed to taper the ends of polymer monolith-containing silica capillaries for use as ESI emitters. Inmore » contrast to previous work, the monolithic material protrudes beyond the fused silica capillaries, improving the monolith-assisted electrospray process.« less

Authors:
; ; ; ; ; ;
Publication Date:
Research Org.:
Pacific Northwest National Laboratory (PNNL), Richland, WA (US), Environmental Molecular Sciences Laboratory (EMSL)
Sponsoring Org.:
USDOE
OSTI Identifier:
896066
Report Number(s):
PNNL-SA-50640
17797; KP1601010
DOE Contract Number:
AC05-76RL01830
Resource Type:
Journal Article
Resource Relation:
Journal Name: Analytical Chemistry, 78(22):7796-7801
Country of Publication:
United States
Language:
English
Subject:
Electrospray; nanoelectrospray; monolith-assisted electrospray; chemical etching; silica; emitter; mass spectrometry; Environmental Molecular Sciences Laboratory

Citation Formats

Kelly, Ryan T., Page, Jason S., Luo, Quanzhou, Moore, Ronald J., Orton, Daniel J., Tang, Keqi, and Smith, Richard D.. Chemically Etched Open Tubular and Monolithic Emitters for Nanoelectrospray Ionization Mass Spectrometry. United States: N. p., 2006. Web. doi:10.1021/ac0521394.
Kelly, Ryan T., Page, Jason S., Luo, Quanzhou, Moore, Ronald J., Orton, Daniel J., Tang, Keqi, & Smith, Richard D.. Chemically Etched Open Tubular and Monolithic Emitters for Nanoelectrospray Ionization Mass Spectrometry. United States. doi:10.1021/ac0521394.
Kelly, Ryan T., Page, Jason S., Luo, Quanzhou, Moore, Ronald J., Orton, Daniel J., Tang, Keqi, and Smith, Richard D.. 2006. "Chemically Etched Open Tubular and Monolithic Emitters for Nanoelectrospray Ionization Mass Spectrometry". United States. doi:10.1021/ac0521394.
@article{osti_896066,
title = {Chemically Etched Open Tubular and Monolithic Emitters for Nanoelectrospray Ionization Mass Spectrometry},
author = {Kelly, Ryan T. and Page, Jason S. and Luo, Quanzhou and Moore, Ronald J. and Orton, Daniel J. and Tang, Keqi and Smith, Richard D.},
abstractNote = {We have developed a new procedure for fabricating fused silica emitters for electrospray ionization-mass spectrometry (ESI-MS) in which the end of a bare fused silica capillary is immersed into aqueous hydrofluoric acid, and water is pumped through the capillary to prevent etching of the interior. Surface tension causes the etchant to climb the capillary exterior, and the etch rate in the resulting meniscus decreases as a function of distance from the bulk solution. Etching continues until the silica touching the hydrofluoric acid reservoir is completely removed, essentially stopping the etch process. The resulting emitters have no internal taper, making them much less prone to clogging compared to e.g. pulled emitters. The high aspect ratios and extremely thin walls at the orifice facilitate very low flow rate operation; stable ESI-MS signals were obtained for model analytes from 5-μm-diameter emitters at a flow rate of 5 nL/min with a high degree of inter-emitter reproducibility. In extensive evaluation, the etched emitters were found to enable approximately four times as many LC-MS analyses of proteomic samples before failing compared with conventional pulled emitters. The fabrication procedure was also employed to taper the ends of polymer monolith-containing silica capillaries for use as ESI emitters. In contrast to previous work, the monolithic material protrudes beyond the fused silica capillaries, improving the monolith-assisted electrospray process.},
doi = {10.1021/ac0521394},
journal = {Analytical Chemistry, 78(22):7796-7801},
number = ,
volume = ,
place = {United States},
year = 2006,
month =
}
  • An array of emitters has been developed for increasing the sensitivity of electrospray ionization mass spectrometry (ESI-MS). The linear array consists of 19 chemically etched fused silica capillaries arranged with 500 µm (center-to-center) spacing. The multi-emitter device has a low dead volume to facilitate coupling to capillary liquid chromatography (LC) separations. The high aspect ratio of the emitters enables operation at flow rates as low as 20 nL/min/emitter, effectively extending the benefits of nanoelectrospray to higher flow rate analyses. To accommodate the larger ion current produced by the emitter array, a multi-capillary inlet to the mass spectrometer was also constructed.more » The inlet, which matched the dimensions of the emitter array, effectively preserved ion transmission efficiency. Standard reserpine solutions of varying concentration were electrosprayed at 1 µL/min using the multi-emitter/multi-inlet combination, and compared to a standard, single emitter configuration. A nine-fold sensitivity enhancement was observed for the multi-emitter relative to the single emitter. A bovine serum albumin tryptic digest was also analyzed and resulted in a sensitivity increase ranging from 2.4 to 12.3-fold for the detected tryptic peptides; the varying response was attributed to reduced ion suppression under the nano-ESI conditions afforded by the emitter array. An equimolar mixture of leucine enkephalin and maltopentaose was studied to verify that ion suppression is indeed reduced for the multi-ESI array relative to a single emitter over a range of flow rates.« less
  • Electrospray ionization mass spectrometry (ESI-MS) at flow rates below ~10 nL/min has been only sporadically explored due to difficulty in reproducibly fabricating emitters that can operate at lower flow rates. Here we demonstrate narrow orifice chemically etched emitters for stable electrospray at flow rates as low as 400 pL/min. Depending on the analyte concentration, we observe two types of MS signal response as a function of flow rate. At low concentrations, an optimum flow rate is observed slightly above 1 nL/min, while the signal decreases monotonically with decreasing flow rates at higher concentrations. In spite of lower MS signal, themore » ion utilization efficiency increases exponentially with decreasing flow rate in all cases. No unimolecular response was observed within this flow rate range during the analysis of an equimolar mixture of peptides, indicating that ionization efficiency is an analyte-dependent characteristic in given experimental conditions. While little to no gain in signal-to-noise was achieved at ultralow flow rates for concentration-limited analyses, experiments consuming the same amount of analyte suggest that mass-limited analyses will benefit strongly from the use of low flow rates and avoiding unnecessary sample dilution. By operating under optimal conditions, consumption of just 500 zmol of sample yielded signal-to-noise ratios ~10 for some peptides. These findings have important implications for the analysis of trace biological samples.« less
  • Poly(dimethylsiloxane) (PDMS) is the most widely used substrate for microfluidic devices as it enables facile fabrication and has other distinctive properties. However, for applications involving highly sensitive nanoelectrospray ionization mass spectrometry (nanoESI-MS) detection, the use of PDMS microdevices has been hindered by the leaching of uncross-linked oligomers and other contaminants from the substrate that yields a large background of chemical noise in the mass spectra. A more general challenge is that microfluidic devices containing integrated electrospray emitters are frequently unable to operate stably in the nanoflow regime where the best sensitivity is achieved. In this report, we extracted the contaminantsmore » from PDMS substrates using a series of solvents, eliminating the background observed when untreated PDMS microchips are used for nanoESI-MS. Optimization of the integrated emitter geometry enabled stable operation at flow rates as low as 10 nL/min. Peptide concentrations of 1 nM were readily detected, representing ~170 zmol of consumed analyte, and an extrapolated detection limit of ~40 zmol; these are the lowest mass and concentration detection limits reported to date for a microchip having an integrated electrospray emitter.« less
  • Novel and significantly simplified procedures for fabrication of fully integrated nanoelectrospray emitters have been described. For nanofabricated monolithic multinozzle emitters (NM.sup.2 emitters), a bottom up approach using silicon nanowires on a silicon sliver is used. For microfabricated monolithic multinozzle emitters (M.sup.3 emitters), a top down approach using MEMS techniques on silicon wafers is used. The emitters have performance comparable to that of commercially-available silica capillary emitters for nanoelectrospray mass spectrometry.