@article{robichaud_dixon_potturi_cassidy_edwards_sohn_dow_muddiman_2011, title={Design, modeling, fabrication, and evaluation of the air amplifier for improved detection of biomolecules by electrospray ionization mass spectrometry}, volume={300}, ISSN={["1873-2798"]}, DOI={10.1016/j.ijms.2010.04.006}, abstractNote={Through a multi-disciplinary approach, the air amplifier is being evolved as a highly engineered device to improve detection limits of biomolecules when using electrospray ionization. Several key aspects have driven the modifications to the device through experimentation and simulations. We have developed a computer simulation that accurately portrays actual conditions and the results from these simulations are corroborated by the experimental data. These computer simulations can be used to predict outcomes from future designs resulting in a design process that is efficient in terms of financial cost and time. We have fabricated a new device with annular gap control over a range of 50 to 70 μm using piezoelectric actuators. This has enabled us to obtain better aerodynamic performance when compared to the previous design (2× more vacuum) and also more reproducible results. This is allowing us to study a broader experimental space than the previous design which is critical in guiding future directions. This work also presents and explains the principles behind a fractional factorial design of experiments methodology for testing a large number of experimental parameters in an orderly and efficient manner to understand and optimize the critical parameters that lead to obtain improved detection limits while minimizing the number of experiments performed. Preliminary results showed that several folds of improvements could be obtained for certain condition of operations (up to 34 folds).}, number={2-3}, journal={INTERNATIONAL JOURNAL OF MASS SPECTROMETRY}, author={Robichaud, Guillaume and Dixon, R. Brent and Potturi, Amarnatha S. and Cassidy, Dan and Edwards, Jack R. and Sohn, Alex and Dow, Thomas A. and Muddiman, David C.}, year={2011}, month={Mar}, pages={99–107} } @article{dixon_bereman_petitte_hawkridge_muddiman_2011, title={One-year plasma N-linked glycome intra-individual and inter-individual variability in the chicken model of spontaneous ovarian adenocarcinoma}, volume={305}, ISSN={["1387-3806"]}, url={http://europepmc.org/abstract/med/21845070}, DOI={10.1016/j.ijms.2010.05.023}, abstractNote={Spontaneous epithelial ovarian cancer (EOC) in the chicken presents a similar pathogenesis compared with humans including CA-125 expression and genetic mutational frequencies (e.g., p53). The high prevalence of spontaneous EOC chickens also provides a unique experimental model for biomarker discovery at the genomic, proteomic, glycomic, and metabolomic level. In an effort to exploit this unique model for biomarker discovery, longitudinal plasma samples were collected from chickens at three month intervals for one year. The study described herein involved cleaving the N-glycans from these longitudinal chicken plasma samples and analyzing them via nanoLC-FTMS/MS. Glycans identified in this study were previously found in human plasma and this work provides a promising methodology to enable longitudinal studies of the N-linked plasma glycome profile during EOC progression. The structure, abundance, and intra-variability and inter-variability for 35 N-linked glycans identified in this study are reported. The full potential of the chicken model for biomarker discovery has yet to be realized, but the initial interrogation of longitudinally-procured samples provides evidence that supports the value of this strategy in the search for glycomic biomarkers.}, number={2-3}, journal={INTERNATIONAL JOURNAL OF MASS SPECTROMETRY}, author={Dixon, R. Brent and Bereman, Michael S. and Petitte, James N. and Hawkridge, Adam M. and Muddiman, David C.}, year={2011}, month={Aug}, pages={79–86} } @article{dixon_muddiman_2010, title={Study of the ionization mechanism in hybrid laser based desorption techniques}, volume={135}, ISSN={["0003-2654"]}, DOI={10.1039/b926422a}, abstractNote={In order to study the ionization mechanism in MALDESI, the RASTIR source was implemented to separate in space the laser desorption event from the intersecting electrospray ionization beam. Deuterated solvents were electrosprayed from the RASTIR source which resulted in a near complete shift from [M + H(+)](1+) to [M + D(+)](1+) of the monoisotopic peak for reserpine. The purpose of these experiments is to test the hypothesis that the primary ionization pathway in MALDESI is through interaction of the laser-desorbed neutral species with the intersecting electrospray ionization beam. The combination of RASTIR coupled to MALDESI can be utilized to study small organic molecules as well as peptides and proteins. Moreover, the use of RASTIR combined with MALDESI lends itself to improve the overall efficiency of ionization.}, number={5}, journal={ANALYST}, author={Dixon, R. Brent and Muddiman, David C.}, year={2010}, pages={880–882} } @article{forbes_dixon_muddiman_degertekin_fedorov_2009, title={Characterization of Charge Separation in the Array of Micromachined UltraSonic Electrospray (AMUSE) Ion Source for Mass Spectrometry}, volume={20}, ISSN={["1879-1123"]}, DOI={10.1016/j.jasms.2009.05.006}, abstractNote={An initial investigation into the effects of charge separation in the Array of Micromachined UltraSonic Electrospray (AMUSE) ion source is reported to gain understanding of ionization mechanisms and to improve analyte ionization efficiency and operation stability. In RF-only mode, AMUSE ejects, on average, an equal number of slightly positive and slightly negative charged droplets due to random charge fluctuations, providing inefficient analyte ionization. Charge separation at the nozzle orifice is achieved by the application of an external electric field. By bringing the counter electrode close to the nozzle array, strong electric fields can be applied at relatively low DC potentials. It has been demonstrated, through a number of electrode/electrical potential configurations, that increasing charge separation leads to improvement in signal abundance, signal-to-noise ratio, and signal stability.}, number={9}, journal={JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY}, author={Forbes, Thomas P. and Dixon, R. Brent and Muddiman, David C. and Degertekin, F. Levent and Fedorov, Andrei G.}, year={2009}, month={Sep}, pages={1684–1687} } @article{dixon_sampson_muddiman_2009, title={Generation of Multiply Charged Peptides and Proteins by Radio Frequency Acoustic Desorption and Ionization for Mass Spectrometric Detection}, volume={20}, ISSN={["1879-1123"]}, DOI={10.1016/j.jasms.2008.11.024}, abstractNote={The design and implementation of a radio frequency acoustic desorption ionization (RADIO) source has been demonstrated for the analysis of multiply charged peptides and proteins. One muL aliquots of melittin, BNP-32, and ubiquitin ( approximately 1 mug of analyte) were deposited onto a quartz crystal microbalance (QCM) electrode before radio frequency actuation for desorption. Continuous electrospray parallel to/above the sampling surface enabled the ionization of desorbed species. Detection by a hybrid linear ion trap Fourier transform ion cyclotron resonance mass spectrometer confirmed the intact and dissociated species observed during MS and MS/MS experiments, respectively.}, number={4}, journal={JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY}, author={Dixon, R. Brent and Sampson, Jason S. and Muddiman, David C.}, year={2009}, month={Apr}, pages={597–600} } @article{dixon_sampson_hawkridge_muddiman_2008, title={Ambient aerodynamic ionization source for remote analyte sampling and mass spectrometric analysis}, volume={80}, ISSN={["1520-6882"]}, DOI={10.1021/ac800289f}, abstractNote={The use of aerodynamic devices in ambient ionization source development has become increasingly prevalent in the field of mass spectrometry. In this study, an air ejector has been constructed from inexpensive, commercially available components to incorporate an electrospray ionization emitter within the exhaust jet of the device. This novel aerodynamic device, herein termed remote analyte sampling, transport, and ionization relay (RASTIR) was used to remotely sample neutral species in the ambient and entrain them into an electrospray plume where they were subsequently ionized and detected using a linear ion trap Fourier transform mass spectrometer. Two sets of experiments were performed in the ambient environment to demonstrate the device's utility. The first involved the remote (approximately 1 ft) vacuum collection of pure sample particulates (i.e., dry powder) from a glass slide, entrainment and ionization at the ESI emitter, and mass spectrometric detection. The second experiment involved the capture (vacuum collection) of matrix-assisted laser desorbed proteins followed by entrainment in the ESI emitter plume, multiple charging, and mass spectrometric detection. This approach is in principle a RASTIR-assisted matrix-assisted laser desorption electrospray ionization source (Sampson, J. S.; Hawkridge, A. M.; Muddiman, D. C. J. Am. Soc. Mass Spectrom. 2006, 17, 1712-1716; Rapid Commun. Mass Spectrom. 2007, 21, 1150-1154.). A detailed description of the device construction, operational parameters, and preliminary small molecule and protein data are presented.}, number={13}, journal={ANALYTICAL CHEMISTRY}, author={Dixon, R. Brent and Sampson, Jason S. and Hawkridge, Adam M. and Muddiman, David C.}, year={2008}, month={Jul}, pages={5266–5271} } @article{bereman_lyndon_dixon_muddiman_2008, title={Mass measurement accuracy comparisons between a double-focusing magnetic sector and a time-of-flight mass analyzer}, volume={22}, ISSN={["0951-4198"]}, DOI={10.1002/rcm.3544}, abstractNote={Abstract}, number={10}, journal={RAPID COMMUNICATIONS IN MASS SPECTROMETRY}, author={Bereman, Michael S. and Lyndon, Matthew M. and Dixon, R. Brent and Muddiman, David C.}, year={2008}, month={May}, pages={1563–1566} } @article{dixon_muddiman_hawkridge_fedorov_2007, title={Probing the mechanisms of an air amplifier using a LTQ-FT-ICR-MS and fluorescence spectroscopy}, volume={18}, ISSN={["1879-1123"]}, DOI={10.1016/j.jasms.2007.08.006}, abstractNote={We report the first quantitative assessment of electrosprayed droplet/ion focusing enabled by the use of a voltage-assisted air amplifier between an electrospray ionization emitter and a hybrid linear ion trap Fourier transform ion cyclotron resonance mass spectrometer (ESI-LTQ-FT-ICR-MS). A solution of fluorescent dye was electrosprayed with a stainless steel mesh screen placed in front of the MS inlet capillary acting as a gas-permeable imaging plate for fluorescence spectroscopy. Without use of the air amplifier, no detectable FT-ICR signal was observed, as well as no detectable fluorescence on the screen upon imaging using a fluorescence scanner. When the air amplifier was turned ON while electrospraying the fluorescent dye, FT-ICR mass spectra with high signal to noise ratio were obtained with an average ion injection time of 21 ms for an AGC target value of 5 x 10(5). Imaging of the screen using a fluorescence scanner produced a distinct spot of cross-sectional area approximately 33.5 mm(2) in front of the MS inlet capillary. These experimental results provide direct evidence of aerodynamic focusing of electrosprayed droplets/ions enabled by an air amplifier, resulting in improved electrospray droplet/ion capture efficiency and reduced ion injection time. A second set of experiments was carried out to explore whether the air amplifier assists in desolvation. By electrospraying a mix of quaternary amines, ratios of increasingly hydrophobic molecules were obtained. Observation of the solvophobic effect associated with electrospray ionization resulted in a higher abundance of the hydrophobic molecule. This bias was eliminated when the air amplifier was turned ON and a response indicative of the respective component concentrations of the molecules in the bulk solution was observed.}, number={11}, journal={JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY}, author={Dixon, R. Brent and Muddiman, David C. and Hawkridge, Adam M. and Fedorov, A. G.}, year={2007}, month={Nov}, pages={1909–1913} } @article{dixon_bereman_muddiman_hawkridge_2007, title={Remote mass spectrometric sampling of electrospray- and desorption electrospra-generated ions using an air ejector}, volume={18}, DOI={10.1016/i.jasms.2007.07.024}, number={10}, journal={Journal of the American Society for Mass Spectrometry}, author={Dixon, R. B. and Bereman, M. S. and Muddiman, David and Hawkridge, A. M.}, year={2007}, pages={1844–1847} }