Nanoelectrospray emitters

Miniaturized columns have provided a decisive advantage in speed. Uracil, phenol, and benzyl alcohol were separated in 20 seconds by CEC in an 18 mm column with a propyl reversed phase.29 A19 cm electrophoretic channel was etched into a glass wafer, filled with a y-cyclodextrin buffer, and used to resolve chiral amino acids from a meteorite in 4 minutes.30 A 6 cm channel equipped with a syringe pump to automate sample derivatization was used to separate amino acids modified with fluorescein isothiocyanate.31 Nanovials have been used to perform tryptic digests on the 15 nL scale for subsequent separation on capillary Electrophoresis.32 A microcolumn has also been used to generate fractions representing time-points of digestion from a 40 pL sample.33 A disposable nanoelectrospray emitter has been... 

Zampronio, C.G. Giannakopulos, A.E. Zeller, M. Bitziou, E. Macpherson, J.V. Derrick, P.J. Production and properties of nanoelectrospray emitters used in fourier transform ion cyclotron resonance mass spectrometry implications for determination of association constants for noncovalent complexes. Anal. Chem. 2004, 76, 5172-5179. 

Ghitun et al. [25] used nano-HPLC for the analysis of complex protein digests by integrating a 30 nL precolumn (trap) and a 10 pm i.d. nanoelectrospray emitter coupled with a TOF-MS. The separation channel was of 45 x 0.075 x 0.050 mm dimension packed with either Zorbax C 8 or C3 of... 

In addition, a pulled capillary tip was inserted and glued to the end of a microchannel to be used as a disposable nanoelectrospray emitter. Membrane... 

Le Gac, S., Arscott, S., Rolando, C., A planar microfabricated nanoelectrospray emitter tip based on a capillary slot. Electrophoresis 2003, 24, 3640-3647. 

FIGURE 3A Schematic representation of the chip-CE configuration using a disposable nanoelectrospray emitter interfaced to either a triple quadrupole or a hybrid quadrupole TOF mass spectrometer. Reprinted with permission from [56]. Copyright 2000, The American Chemical Society. 

Micro fabricated Nanoelectrospray Emitter Tips based on a Microfluidic Capillary Slot... 

The present microfluidic device differs slightly from similar systems previously reported by our group.34 36 The chip device integrates a 40 nL enrichment column, a 4.3 cm analytical column (75 x 50 pm cross-section channel) and a 10 pm i.d. nanoelectrospray emitter directly on a polymer surface which is itself encased into an aluminium holder for convenient manipulation (Figure 8.1a). An on-line filter (0.5 pm pore size) is positioned between the valve stator and the nanopump to prevent occlusion of the chip device. The chip is mounted in a... 

In a similar effort to combine preconcentration with electrophoretic separations, Fortier et al. [123] investigated the analytical performances of a microfluidic system comprised of an enrichment column, a reversed phase separation channel, and a nanoelectrospray emitter embedded together in polyimide layers. The authors demonstrated that the configuration minimized transfer lines and connections and reduced peak broadening and dead volumes, resulting in good reproducibility of retention time and peak intensity. The microchip was interfaced to both ion trap and TOF MS. Measurements were performed for a dilution series of protein digests spiked into rat plasma samples and provided an LOD of 1-5 fmol. 

Recent work, however, has expanded the breadth of DMF applications. Despite the natural match with MALDI, some authors have shown that DMF platforms could also be successfully interfaced with the MS by using ESI [15-17]. In particular, Shih et al. [15] developed a platform for MS analysis of dried blood spots. As shown in Fig. 4, a pulled-glass capillary nanoelectrospray emitter was directly inserted between the two plates of a DMF device. This work paves the way for high-throughput analysis of complex samples using digital microfluidics. 

Bateman, K. P., White, R. L., and Thibault, P. (1997). Disposable emitters for online capillary zone electrophoresls/nanoelectrospray mass spectrometry. Rapid Commun. Mass Spectrom. 11, 307-315. 

Very low flow electrospray is called nanoelectrospray [26] where the samples are infused into the mass spectrometer at the nanoliter flow rate range. The infusion of a few microliters will result in a stable signal for more then 30 min, using pulled capillaries or chip-based emitters [27]. With infusion, signal averaging allows to improve the limit of detection in tandem mass spectrometry. Nanoelectrospray is particularly important in combination with nanoflow liquid chromatography or chip-based infusion for the analysis of peptides and proteins. 

Nanoelectrospray ionization flow rates range from a few nanoliters per minutes to a few hundred nanoliters per minutes nanoelectrospray is performed with pulled capillaries or on chips which serve as emitter... 

Kim W, Guo M, Yang P, Wang D (2007) Mitaofabiicated monolithic multinozzle emitters for nanoelectrospray mass spectrometry. Anal Chem 79 3703-3707... 

Sun XF, Kelly RT, Tang KQ, Smith RD (2011) Membrane-based emitter for coupling microlluidics with ultrasensitive nanoelectrospray ionization-mass spectrometry. Anal Chem 83(14) 5797-5803... 

Interfaces Between Microfluidics and Mass Spectrometry, Fig. 4 Digital microfluidics - nanoelectrospray interface, (a) Image showing the dried blood spot (DBS) and droplets sitting on actuation electrodes. The device couples directly with the nanospray (capillary) emitter, (b) Side-view schematic of the DMF device. The application... 

Kirby, A.E., Jebrail, M.J., Yang, H., Wheeler, A.R. (2010) Folded Emitters for Nanoelectrospray Ionization Mass Spectrometry. Rapid Commun. Mass Spectrom. 24 3425-3431. 

Mao, P, Wang, H.-T., Yang, P, Wang, D. (2011) Multinozzle Emitter Arrays for Nanoelectrospray Mass Spectrometry. Anal. Chem. 83 6082-6089. 

Nanoelectrospray ionization (nanoESI) makes use of gold-coated borosilicate nanospray emitters with approximately 4 pm internal diameter. NanoESI is far less prone to interference from the presence of salts and buffers than its conventional ESI counterpart, while requiring extremely low sample levels (down to the atto-mole level). In nanoESI, the droplets are formed in close proximity to the MS inlet and this fact causes an ionization efficiency enhancement over conventional ESI. This feature is particularly useful when the sample is a mixture. 

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