System and methods for ionizing compounds using matrix-assistance for mass spectrometry and ion mobility spectrometry

Abstract

An ionization method for use with mass spectrometry or ion mobility spectrometry is a small molecule compound(s) as a matrix into which is incorporated analyte. The matrix has attributes of sublimation or evaporation when placed in vacuum at or near room temperature and produces both positive and negative charges. Placing the sample into a region of sub-atmospheric pressure, the region being in fluid communication with the vacuum of the mass spectrometer or ion mobility spectrometer, produces gas-phase ions of the analyte for mass-to-charge or drift-time analysis without use of a laser, high voltage, particle bombardment, or a heated ion transfer region. This matrix and vacuum assisted ionization process can operate from atmosphere or vacuum and produces ions from large (e.g. proteins) and small molecules (e.g. drugs) with charge states similar to those observed in electrospray ionization.

1 .- 39 . (canceled) 
     
     
         40 . A method of ionizing an analyte for analysis by ion mobility spectrometry or mass spectrometry, comprising:
 providing a sample comprising an analyte and a matrix, wherein the matrix is 3-nitrobenzonitrile, 2-nitrobenzonitrile, 5-methyl-2-nitrobenzonitrile, coumarin, methyl-2-methyl-3-nitrobenzoate, methyl-5-nitro-2-furoate, 2-bromo-2-nitropropane-1,3-diol, 3-nitrobenzaldehyde, 6-nitro-o-anisonitrile, phthalic anhydride, or mixtures thereof;   producing gas phase positive or negative ions of the analyte without irradiating the sample with a laser and without exposing the sample to high velocity particles to produce the gas phase positive or negative ions of the analyte.   
     
     
         41 . The method of  claim 40 , further comprising the step of cooling or heating the sample to a temperature between −80° C. and 150° C. 
     
     
         42 . The method of  claim 41 , wherein the temperature is between 25° C. and 80° C. 
     
     
         43 . The method of  claim 40 , further comprising the step of exposing the sample to sub-atmospheric pressure. 
     
     
         44 . The method of  claim 43 , wherein said sub-atmospheric pressure is between 750 mm Hg and 1×10 −7  Hg. 
     
     
         45 . The method of  claim 40 , wherein said gas phase positive or negative ions of the analyte are singly or multiply charged. 
     
     
         46 . The method of  claim 40 , wherein the step of producing gas-phase positive or negative ions of the analyte is a spontaneous process. 
     
     
         47 . The method of  claim 40 , wherein said matrix sublimes or evaporates when exposed to sub-atmospheric pressure. 
     
     
         48 . The method of  claim 40 , wherein said matrix sublimes or evaporates when exposed to sub-atmospheric pressure at a temperature of less than 70° C. 
     
     
         49 . The method of  claim 40 , wherein said analyte is a biofilm, biological tissue, biological material, edible goods, polymers, paintings, synthetic compounds, archeological artifacts, artificial bone, skin, urine or blood. 
     
     
         50 . The method of  claim 40 , wherein said analyte is selected from proteins, protein complexes, receptors, ligands, polymers, catalysts, lipids, drugs, metabolites, pesticides, peptides, chemically or post-translationally modified peptides or proteins, DNA, RNA, carbohydrates, glycans, antibodies, biomarkers or compounds produced by synthesis. 
     
     
         51 . The method of  claim 40 , further comprising the step of placing said sample on a substrate. 
     
     
         52 . The method of  claim 51 , wherein said substrate is comprised of tissue, metal, paper cloth, ribbon, glass, plastic, polymers, sodium dodecyl sulfate gel, paper chromatography plate, silica plate or woven fiber. 
     
     
         53 . The method of  claim 51 , wherein the substrate is the sample. 
     
     
         54 . The method of  claim 40 , wherein said sample further comprises a solvent. 
     
     
         55 . The method of  claim 54 , wherein said solvent is water, methanol, ethanol, isopropanol, acetonitrile, tetrahydrofuran, chloroform, dimethylformamide, dimethyl sulfoxide, acetone, or mixtures thereof. 
     
     
         56 . The method of  claim 40 , wherein said sample is prepared by mixing or grinding the analyte and matrix together, 
     
     
         57 . The method of  claim 40 , wherein said sample is a solid. 
     
     
         58 . The method of  claim 40 , wherein said sample is in a frozen state. 
     
     
         59 . The method of  claim 40 , wherein said sample further comprises an ammonium salt, metal salt, acid, base or buffer.