Title: A Combination MAI and MALDI Vacuum Source Operational from Atmospheric Pressure for Fast, Robust, and Sensitive Analyses
Previously, vacuum matrix-assisted ionization (vMAI) was employed with matrix:analyte sample introduction into the vacuum of the mass spectrometer on a probe sample introduction device. Low attomole detection was achieved while no carryover was observed even for concentrated samples. Here, we report a new vacuum ionization source designed to duplicate the sensitivity and robustness of probe device while providing fast multi-sample introduction to vacuum and rapid sequential ionization. Exposure of a sample to the vacuum of the mass spectrometer provides spontaneous ionization of volatile as well as nonvolatile analytes without the need of external energy input. However, the novel source design described herein, in addition to vMAI, can employ a laser to obtain vacuum matrix-assisted laser desorption/ionization (vMALDI). In particular, ionization by vMAI or vMALDI is achieved by using the appropriate matrix. Switching between ionization modes is accomplished in a few seconds. We present results demonstrating the utility of the two ionization methods in combination to improve molecular analyses of sample composition. In both ionization modes, multiple samples can be sequentially and rapidly acquired to increase throughput in MS. With the prototype source, samples were acquired in as little as 1 second per sample. Exchanging multi-sample plates can be accomplished in as little as 2 seconds suggesting low-cost high throughput automation when properly developed. more »« less
Trimpin, Sarah; Moreno-Pedraza, Abigail; Hoang, Khoa; Pophristic, Milan; Inutan, Ellen D; Marshall, Darrell D; Karki, Santosh; Meher, Anil; Yenchick, Frank S; Lee, Chupiong; et al
(, 68th Annual ASMS Conference on Mass Spectrometry and Allied Topics)
null
(Ed.)
Unprecedented ionization processes developed into powerful methods have attributes highly desirable for MS and include high sensitivity, low cost, simplicity, ability to directly analyze biological and synthetic materials, potential for high throughput, automation, exceptional robustness, and wide applicability, especially in environments outside analytical laboratories. Initial matrix-assisted ionization (MAI) results showed different selectivity relative to ESI or MALDI providing information not readily obtained with current methodologies. Here, we demonstrate the first vacuum ionization source with multi-ionization capabilities on the same high-resolution API-mass spectrometer for a range of analytical problems with sensitivity in low fmol and detection limit in low amol ranges. The potential for achieving MS and MS/MS analysis speeds of ca. 4 seconds/sample in a simple low-cost fashion is demonstrated.
Trimpin, Sarah; Marshall, Darrell_D; Karki, Santosh; Madarshahian, Sara; Hoang, Khoa; Meher, Anil_K; Pophristic, Milan; Richards, Alicia_L; Lietz, Christopher_B; Fischer, Joshua_L; et al
(, Rapid Communications in Mass Spectrometry)
RationaleThe developments of new ionization technologies based on processes previously unknown to mass spectrometry (MS) have gained significant momentum. Herein we address the importance of understanding these unique ionization processes, demonstrate the new capabilities currently unmet by other methods, and outline their considerable analytical potential. MethodsTheinletandvacuumionization methods of solvent‐assisted ionization (SAI), matrix‐assisted ionization (MAI), and laserspray ionization can be used with commercial and dedicated ion sources producing ions from atmospheric or vacuum conditions for analyses of a variety of materials including drugs, lipids, and proteins introduced from well plates, pipet tips and plate surfaces with and without a laser using solid or solvent matrices. Mass spectrometers from various vendors are employed. ResultsResults are presented highlighting strengths relative to ionization methods of electrospray ionization (ESI) and matrix‐assisted laser desorption/ionization. We demonstrate the utility of multi‐ionization platforms encompassing MAI, SAI, and ESI and enabling detection of what otherwise is missed, especially when directly analyzing mixtures. Unmatched robustness is achieved with dedicated vacuum MAI sources with mechanical introduction of the sample to the sub‐atmospheric pressure (vacuumMAI). Simplicity and use of a wide array of matrices are attained using a conduit (inletionization), preferably heated, with sample introduction from atmospheric pressure. Tissue, whole blood, urine (including mouse, chicken, and human origin), bacteria strains and chemical on‐probe reactions are analyzed directly and, especially in the case ofvacuumionization, without concern of carryover or instrument contamination. ConclusionsExamples are provided highlighting the exceptional analytical capabilities associated with the novel ionization processes in MS that reduce operational complexity while increasing speed and robustness, achieving mass spectra with low background for improved sensitivity, suggesting the potential of this simple ionization technology to drive MS into areas currently underserved, such as clinical and medical applications.
Inutan, Ellen_D; Meher, Anil_K; Karki, Santosh; Fischer, Joshua_L; Imperial, Lorelie_F; Foley, Casey_D; Jarois, Dean_R; El‐Baba, Tarick_J; Lutomski, Corinne_A; Trimpin, Sarah
(, Rapid Communications in Mass Spectrometry)
RationaleNew ionization processes have been developed for biological mass spectrometry (MS) in which the matrix lifts the nonvolatile analyte into the gas phase as ions without any additional energy input. We rationalized that additional fundamental knowledge is needed to assess analytical utility for the field of synthetic polymers and additives. MethodsDifferent mass spectrometers (Thermo Orbitrap (Q‐)Exactive (Focus); Waters SYNAPT G2(S)) were employed. The formation of multiply charged polymer ions upon exposure of the matrix/analyte(/salt) sample to sub‐atmospheric pressure directly from the solid state and surfaces facilitates the use of advanced mass spectrometers for detection of polymeric materials including consumer products (e.g., gum). ResultsAstonishingly, using nothing more than a small molecule matrix compound (e.g., 2‐methyl‐2‐nitropropane‐1,3‐diol or 3‐nitrobenzonitrile) and a salt (e.g., mono‐ or divalent cation(s)), such samples upon exposure to sub‐atmospheric pressure transfer nonvolatile polymersandnonvolatile salts into the gas phase as multiply charged ions. These successes contradict the conventional understanding of ionization in MS, because can nonvolatile polymers be lifted in the gas phase as ions not only by as little as a volatile matrix but also by the salt required for ionizing the analyte through noncovalent metal cation adduction(s). Prototypevacuummatrix‐assisted ionization (vMAI) and automated sources using a contactless approach are demonstrated for direct analyses of synthetic polymers and plasticizers, minimizing the risk of contamination using direct sample introduction into the mass spectrometer vacuum. ConclusionsDirect ionization methods from surfaces without the need of high voltage, a laser, or even applied heat are demonstrated for characterization of detailed materials using (ultra)high‐resolution and accurate mass measurements enabled by the multiply charged ions extending the mass range of high‐performance mass spectrometers and use of a split probe sample introduction device. Our vision is that, with further development of fundamentals and dedicated sources, both spatial‐ and temporal‐resolution measurements are within reach if sensitivity is addressed for decreasing sample‐size measurements.
Hoang, Khoa; Pophristic, Milan; Karki, Santosh; Marshall, Darrell D.; Trimpin, Sarah; McEwen, Charles N.
(, 68th Annual ASMS Conference on Mass Spectrometry and Allied Topics)
Here we present advances in automated multi-ionization mass spectrometry (MS). The Ionique platform offers ESI, matrix-assisted ionization (MAI) and solvent-assisted ionization (SAI). A novel high throughput manual ion source is also presented.
Xin, Yue; Foster, Samuel W; Makey, Devin M; Parker, Deklin; Bradow, James; Wang, Xiaochun; Berritt, Simon; Mongillo, Robert; Grinias, James P; Kennedy, Robert T
(, Analytical Chemistry)
The cycle time of a standard liquid chromatography (LC) system is the sum of the time for the chromatographic run and the autosampler injection sequence. Although LC separation times in the 1-10 s range have been demonstrated, injection sequences are commonly >15 s, limiting throughput possible with LC separations. Further, such separations are performed on relatively large bore columns requiring flow rates of ≥5 mL/min, thus generating large volumes of mobile phase waste when used for large scale screening and increasing the difficulty in interfacing to mass spectrometry. Here, a droplet injector system was established that replaces the autosampler with a four-port, two-position valve equipped with a 20 nL internal loop interfaced to a syringe pump and a three-axis positioner to withdraw sample droplets from a well plate. In the system, sample and immiscible fluid are pulled alternately from a well plate into a capillary and then through the injection valve. The valve is actuated when sample fills the loop to allow sequential injection of samples at high throughput. Capillary LC columns with 300 μm inner diameter were used to reduce the consumption of mobile phase and sample. The system achieved 96 separations of 20 nL droplet samples containing 3 components in as little as 8.1 min with 5-s cycle time. This system was coupled to a mass spectrometer through an electrospray ionization source for high-throughput chemical reaction screening.
Hoang, Khoa., Trimpin, Sarah, McEwen, Charles N., and Pophristic, Milan. A Combination MAI and MALDI Vacuum Source Operational from Atmospheric Pressure for Fast, Robust, and Sensitive Analyses. Retrieved from https://par.nsf.gov/biblio/10202779. Journal of the American Society for Mass Spectrometry . Web. doi:10.1021/jasms.0c00298.
Hoang, Khoa., Trimpin, Sarah, McEwen, Charles N., & Pophristic, Milan. A Combination MAI and MALDI Vacuum Source Operational from Atmospheric Pressure for Fast, Robust, and Sensitive Analyses. Journal of the American Society for Mass Spectrometry, (). Retrieved from https://par.nsf.gov/biblio/10202779. https://doi.org/10.1021/jasms.0c00298
Hoang, Khoa., Trimpin, Sarah, McEwen, Charles N., and Pophristic, Milan.
"A Combination MAI and MALDI Vacuum Source Operational from Atmospheric Pressure for Fast, Robust, and Sensitive Analyses". Journal of the American Society for Mass Spectrometry (). Country unknown/Code not available. https://doi.org/10.1021/jasms.0c00298.https://par.nsf.gov/biblio/10202779.
@article{osti_10202779,
place = {Country unknown/Code not available},
title = {A Combination MAI and MALDI Vacuum Source Operational from Atmospheric Pressure for Fast, Robust, and Sensitive Analyses},
url = {https://par.nsf.gov/biblio/10202779},
DOI = {10.1021/jasms.0c00298},
abstractNote = {Previously, vacuum matrix-assisted ionization (vMAI) was employed with matrix:analyte sample introduction into the vacuum of the mass spectrometer on a probe sample introduction device. Low attomole detection was achieved while no carryover was observed even for concentrated samples. Here, we report a new vacuum ionization source designed to duplicate the sensitivity and robustness of probe device while providing fast multi-sample introduction to vacuum and rapid sequential ionization. Exposure of a sample to the vacuum of the mass spectrometer provides spontaneous ionization of volatile as well as nonvolatile analytes without the need of external energy input. However, the novel source design described herein, in addition to vMAI, can employ a laser to obtain vacuum matrix-assisted laser desorption/ionization (vMALDI). In particular, ionization by vMAI or vMALDI is achieved by using the appropriate matrix. Switching between ionization modes is accomplished in a few seconds. We present results demonstrating the utility of the two ionization methods in combination to improve molecular analyses of sample composition. In both ionization modes, multiple samples can be sequentially and rapidly acquired to increase throughput in MS. With the prototype source, samples were acquired in as little as 1 second per sample. Exchanging multi-sample plates can be accomplished in as little as 2 seconds suggesting low-cost high throughput automation when properly developed.},
journal = {Journal of the American Society for Mass Spectrometry},
author = {Hoang, Khoa. and Trimpin, Sarah and McEwen, Charles N. and Pophristic, Milan},
}
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