Matrix Assisted Ionization in Vacuum, a Sensitive and Widely Applicable Ionization Method for Mass Spectrometry

Abstract

An astonishingly simple new method to produce gas-phase ions of small molecules as well as proteins from the solid state under cold vacuum conditions is described. This matrix assisted ionization vacuum (MAIV) mass spectrometry (MS) method produces multiply charged ions similar to those that typify electrospray ionization (ESI) and uses sample preparation methods that are nearly identical to matrix-assisted laser desorption/ionization (MALDI). Unlike these established methods, MAIV does not require a laser or voltage for ionization, and unlike the recently introduced matrix assisted ionization inlet method, does not require added heat. MAIV-MS requires only introduction of a crystalline mixture of the analyte incorporated with a suitable small molecule matrix compound such as 3-nitrobenzonitrile directly to the vacuum of the mass spectrometer. Vacuum intermediate pressure MALDI sources and modified ESI sources successfully produce ions for analysis by MS with this method. As in ESI-MS, ion formation is continuous and, without a laser, little chemical background is observed. MAIV, operating from a surface offers the possibility of significantly improved sensitivity relative to atmospheric pressure ionization because ions are produced in the vacuum region of the mass spectrometer eliminating losses associated with ion transfer from atmospheric pressure to vacuum. Mechanistic aspects and potential applications for this new ionization method are discussed.

Improving the Sensitivity of Matrix-Assisted Ionization (MAI) Mass Spectrometry Using Ammonium Salts

“…The matrices bronopol, 1,2-DCB, and 3-NBN produce multiply charged analyte ions with a room temperature inlet tube when the matrix/analyte sample is directly exposed to low pressure conditions [2,3]. However, improved ion abundance is obtained using the Orbitrap Exactive for shorter duration when heat is applied to the inlet [18].…”

“…M atrix-assisted ionization (MAI), which includes matrix assisted ionization inlet (MAII) and vacuum (MAIV) [1][2][3] produces analyte ions having charge state distributions similar to electrospray ionization (ESI) [4,5]. In MAI, gasphase analyte ions are produced when the analyte in a small molecule matrix compound is exposed to heat [6] and/or the vacuum of the mass spectrometer [2,3].…”

“…In MAI, gasphase analyte ions are produced when the analyte in a small molecule matrix compound is exposed to heat [6] and/or the vacuum of the mass spectrometer [2,3]. Laserspray ionization inlet (LSII) [7] and vacuum (LSIV) [8] are subsets of MAI in which a laser ablates matrix/analyte particles/droplets into the vacuum of the mass spectrometer where ionization occurs, presumably by a similar mechanism as MAI [9].…”

“…The discovery of MAI matrix compounds that spontaneously produce ions from small molecules, peptides, or proteins by simple exposure of matrix/analyte sample to the vacuum at the mass spectrometer inlet aperture, without need of applied heat [2,3], has considerable potential to further simplify ionization in MS. Recently, several additional MAI matrices that operate at low inlet temperature were reported by the Trimpin group [18].…”

Matrix-Assisted Ionization-Ion Mobility Spectrometry-Mass Spectrometry: Selective Analysis of a Europium–PEG Complex in a Crude Mixture

“…The charge separation process in MAI is hypothesized to be a sublimation-driven process through crystal fracturing of compounds that triboluminescence [1,2,10]. Some europiumcontaining compounds are known to triboluminesce [59][60][61][62][63], potentially contributing to the overrepresentation of the europium-containing product.…”