Analyst COMMUNICATION Cite this: Analyst, 2017, 142, 1672 Received 21st March 2017, Accepted 13th April 2017 DOI: 10.1039/c7an00489c rsc.li/analyst Pulsed valve matrix-assisted ionization† Bijay Banstola and Kermit. K. Murray * We have developed a new ionization approach for matrix-assisted ionization with high temporal resolution using an electrically actu- ated pulsed valve. Matrix and analyte samples are deposited on a thin metal foil and placed at the inlet of an ambient ionization mass spectrometer. When the pulsed valve is actuated, a short puff of high pressure gas impinges on the foil and ejects particulate from the sample on the opposite side. Highly charged ions are formed from the particles at the mass spectrometer inlet. Using this source, multiply charged protein ions are produced within a selectable 4 second time window. Introduction Matrix assisted ionization (MAI) is a general term used to describe a mass spectrometer ion source in which ions are formed by the interaction of an analyte molecule with specific matrix compounds that promote the formation of ions. 1–3 As with matrix-assisted laser desorption ionization (MALDI), 4 the matrix is mixed with the analyte and deposited and dried on a sample target. Ion formation is associated with the production of particles by laser ablation, mechanical shock, solvent boiling, or sublimation. 5,6 Some matrix compounds that have been developed for MALDI can also be used for matrix-assisted ionization, but there are many compounds that are unique to MAI. 7 Unlike MALDI, MAI tends to produce ions that are highly charged. 8 MAI has some potential advantages for mass spectrometry imaging due to its simplicity, low fragmentation, and tandem mass spectrometry facilitated by highly charged ion formation. For imaging in laserspray mode, a pulsed laser is directed at a thin tissue section in transmission mode (back side irradiation) to create ions by MAI. 9,10 Matrix-assisted ioniza- tion in vacuum (MAIV) can be used for the analysis of tissue by spotting matrix on selected areas and applying vacuum to the entire tissue section. 11 Precision spotting can limit the exposed tissue area to several hundred μm. An alternative approach uses a glass melting point tube to sample from tissue under ambient conditions for MAI. 12 Better temporal and spatial control of ion formation could add significant utility to these imaging approaches. Precise control of material removal from a metal sample surface for mass spectrometry analysis can be achieved using a locally directed shock pulse. For example, laser induced acous- tic desorption (LIAD) 13 uses a pulsed nanosecond laser that is directed in transmission geometry at a thin metal foil, which ejects material from the opposite side. Post-ionization can be accomplished using electron ionization, 14 electrospray ioniza- tion, 15 and photoionization. 16–18 A similar approach that does not require a laser nebulizes liquid samples from piezoelectric ally driven targets using surface acoustic wave nebulization (SAWN). 19,20 Here a high frequency piezoelectric device is used to nebulize a thin film of liquid from a surface and bare ions are formed upon solvent evaporation and sampled into a mass spectrometer ion source. In this work, we present a method for temporally and spatially localized sampling for matrix-assisted ionization using a solenoid pulsed valve. Here, a high-speed pulsed valve is directed at the back side of a thin foil with a MAI sample on the opposite side facing the inlet of a mass spectrometer. When the valve is actuated, the gas pulse creates a plume of particles, forming ions that are detected in the mass spectro- meter. The pulsed valve matrix-assisted ionization source was demonstrated for ionization of peptide and protein molecules under ambient conditions. Experimental The modified mass spectrometer ion source comprises a pulsed valve that is aimed at the back side of a metal foil that has an inlet ionization matrix and analyte deposited on the front. Ions created at ambient pressure are sampled by the † Electronic supplementary information (ESI) available: Fig. S1 and S2. See DOI: 10.1039/c7an00489c Department of Chemistry, Louisiana State University, Baton Rouge, Louisiana, 70803, USA. E-mail: kkmurray@lsu.edu 1672 | Analyst, 2017, 142, 1672–1675 This journal is © The Royal Society of Chemistry 2017 View Article Online View Journal | View Issue