Probes for a gas phase ion spectrometer

• US 7,205,156 B2
• Filed: 10/06/2004
• Issued: 04/17/2007
• Est. Priority Date: 04/27/1999
• Status: Expired due to Term

• Current Assignee: Bio-Rad Laboratories Incorporated
• Original Assignee: Bio-Rad Laboratories Incorporated
• Inventors: Yip, Tai-Tung, Um, Pil-Je, Rich, William E., Beecher, Jody, Voivodov, Kamen
• Primary Examiner(s): Ahmed; Sheeba
• Application Number:
  US10/960,222
• Publication Number:
  US 20050090016A1
• Time in Patent Office: 923 Days
• Field of Search: None
• US Class Current: 436/173
• CPC Class Codes: H01J 49/0418 for laser desorption, e.g. matrix-assisted laser desorption/ionisation [MALDI] plates or surface enhanced laser desorption/ionisation [SELDI] plates
• CPC Class Codes: H01J 49/12 using an arc discharge, e.g. of the duoplasmatron type
• CPC Class Codes: Y10T 428/261 In terms of molecular thickness or light wave length
• CPC Class Codes: Y10T 428/31504 Composite [nonstructural laminate]
• CPC Class Codes: Y10T 436/24 Nuclear magnetic resonance, electron spin resonance or other spin effects or mass spectrometry

Abstract

The invention provides a probe and a method of making the probe that is removably insertable into a gas phase ion spectrometer, the probe comprising a substrate having a surface and a hydrogel material on the surface, the hydrogel material comprising binding functionalities for binding with an analyte detectable by the gas phase ion spectrometer. The invention also provides a probe and a method of making the probe that is removably insertable into a gas phase ion spectrometer, the probe comprising a substrate having a surface and a plurality of particles that are uniform in diameter on the surface, the particles comprising binding functionalities for binding with an analyte detectable by the gas phase ion spectrometer. Further, the invention provides a system comprising the probe of the present invention and a gas phase ion spectrometer comprising an energy source that directs light to the probe surface to desorb an analyte and a detector in communication with the probe surface that detects the desorbed analyte. The invention also provides a method for desorbing an analyte from a probe surface, the method comprising exposing the binding functionalities to a sample containing an analyte under conditions to allow binding between the analyte and the binding functionalities, and desorbing the analyte from the probe by gas phase ion spectrometry.

Claims

1. A method for detecting an analyte comprising:

(a) providing a probe comprising a substrate having a surface and a hydrogel material on the surface, wherein the hydrogel material comprises a water-insoluble and water-swellable polymer, having absorbed at least 10 times its own weight of a liquid, that is crosslinked and is at least about 10 microns thick and further comprises binding functionalities for binding with an analyte;

(b) exposing the binding functionalities of the hydrogel material to a sample containing an analyte under conditions to allow binding between the analyte and the binding functionalities of the hydrogel material;

(c) striking the probe surface with energy from an ionization source, thereby desorbing and ionizing the analyte;

(d) detecting the desorbed and ionized analyte by mass spectrometry.

2. The method of claim 1 wherein the hydrogel material is derived from substituted acrylamide monomers, substituted acrylate monomers, or derivatives thereof.

3. The method of claim 1 wherein the hydrogel material comprises cellulose or dextran.

4. The method of claim 1 wherein the hydrogel material is derived from 3-(methacryloylamino)propyltrimethylammonium chloride monomers.

5. The method of claim 1 wherein the hydrogel material is derived from 2-acrylamidoglycolic acid monomers.

6. The method of claim 1 wherein the hydrogel material is derived from N-(acrylamidoethyl)ethylenediamine N, N′

, N′

-triacetic acid monomers.

7. The method of claim 1 wherein the binding functionalities attract the analyte by salt-promoted interactions, hydrophilic interactions, eletrostatic interactions, coordinate interactions, covalent interactions, enzyme site interactions, reversible covalent interactions, nonreversible covalent interactions, glycoprotein interactions, biospecific interactions, or combinations thereof.

8. The method of claim 1 wherein the binding functionalities of the hydrogel material are selected from the group consisting of a carboxyl group, a sulfonate group, a phosphate group, an ammonium group, a hydrophilic group, a hydrophobic group, a reactive group, a metal chelating group, a thioether group, a biotin group, a boronate group, a dye group, a cholesterol group, and derivatives thereof.

9. The method of claim 1 wherein the binding functionalities comprise a carboxyl group and the hydrogel material is derived from monomers selected from the group consisting of (meth)acrylic acid, 2-carboxyethyl acrylate, N-acryloyl-aminohexanoic acid, N-carboxymethylacrylamide, 2-acrylamidoglycolic acid, and derivatives thereof.

10. The method of claim 1 wherein the binding functionalities comprise a sulfonate group and the hydrogel material is derived from acrylamidomethyl-propane sulfonic acid monomers or derivatives thereof.

11. The method of claim 1 wherein the binding functionalities comprise a phosphate group and the hydrogel material is derived from N-phosphoethyl acrylamide monomers or derivatives thereof.

12. The method of claim 1 wherein the binding functionalities comprise an ammonium group and the hydrogel material is derived from monomers selected from the group consisting of trimethylaminoethyl methacrylate, diethylaminoethyl methacrylate, diethylaminoethyl acrylamide, diethylaminoethyl methacrylamide, diethylaminopropyl methacrylamide, aminopropyl acrylamide, 3(methacryloylamino)propyltrimethylammonium chloride, 2-aminoethyl methacrylate, N-(3-aminopropyl)methacrylamide, 2-(t-butylamino)ethyl methacrylate, 2-(N, N-dimethylamino)ethyl (meth)acrylate, N-(2-(N, N-dimethylamino))ethyl (meth)acrylamide, N-(3-(N, N-dimethylamino))propyl methacrylamide, 2-(meth)acryloyloxyethyltrimethylammonium chloride, 3-methacryloyloxy-2-hydroxypropyltrimethylammonium chloride, (2-acryloyloxyethyl)(4-benzoylbenzyl)dimethylammonium bromide, 2-vinylpyridine, 4-vinylpyridine, vinylimidazole, and derivatives thereof.

13. The method of claim 1 wherein the binding functionalities comprise a hydrophilic group and the hydrogel material is derived from monomers selected from the group consisting of N-(meth)acryloyltris(hydroxymethyl)methylamine, hydroxyethyl acrylamide, hydroxypropyl methacrylamide, N-acrylamido-1-deoxysorbitol, hydroxyethyl(meth)acrylate, hydroxypropylacrylate, hydroxyphenylmethacrylate, polyethylene glycol monomethacrylate, polyethylene glycol dimethacrylate, acrylamide, glycerol mono(meth)acrylate, 2-hydroxypropyl acrylate, 4-hydroxybutyl methacrylate, 2-methacryloxyethyl glucoside, poly(ethyleneglycol) monomethyl ether monomethacrylate, vinyl 4-hydroxybutyl ether, and derivatives thereof.

14. The method of claim 1 wherein the binding functionalities comprise a hydrophobic group and the hydrogel material is derived from monomers selected from the group consisting of N, N-dimethyl acrylamide, N, N-diethyl (meth)acrylamide, N-methyl methacrylamide, N-ethyl methacrylamide, N-propyl acrylamide, N-butyl acrylamide, N-octyl (meth)acrylamide, N-dodecyl methacrylamide, N-octadecyl acrylamide, propyl (meth)acrylate, decyl (meth)acrylate, stearyl (meth)acrylate, octyl-triphenylmethylacrylamide, butyl-triphenylmethylacrylamide, octadedcyl-triphenylmethylacrylamide, phenyl-triphenylmethylacrylamide, benzyl-triphenylmethylacrylamide, and derivatives thereof.

15. The method of claim 1 wherein the binding functionalities comprise a metal chelating group and the hydrogel material is derived from monomers selected from the group consisting of N-(3-N, N-biscarboxymethylamino)propyl methacrylamide, 5-methacrylamido-2-(N, N-biscarboxymethylamino)pentanoic acid, N-(acrylamidoethyl)ethylenediamine N, N′

, N′

-triacetic acid, and derivatives thereof.

16. The method of claim 1 wherein the binding functionalities comprise a reactive group and the hydrogel material is derived from monomers selected from the group consisting of glycidyl acrylate, acryloyl chloride, glycidyl(meth)acrylate, (meth)acryloyl chloride, N-acryloxysuccinimide, vinyl azlactone, acrylamidopropyl pyridyl disulfide, N-(acrylamidopropyl)maleimide, acrylamidodeoxy sorbitol activated with bis-epoxirane compounds, allylchloroformate, (meth)acrylic anhydride, acrolein, allylsuccinic anhydride, citraconic anhydride, allyl glycidyl ether, and derivatives thereof.

17. The method of claim 1 wherein the binding functionalities comprise a thioether group and the hydrogel material is derived from thiophilic monomers selected from the group consisting of 2-hydroxy-3-mercaptopyridylpropyl (methacrylate), 2-(2-(3-(meth)acryloxyethoxy)ethanesulfonyl)ethylsulfanyl ethanol, and derivatives thereof.

18. The method of claim 1 wherein the binding functionalities comprise a biotin group and the hydrogel material is derived from biotin monomers selected from the group consisting of N-biotinyl-3-(meth)acrylamidopropylamine and derivatives thereof.

19. The method of claim 1 wherein the binding functionalities comprise a boronate group and the hydrogel material is derived from boronate monomers selected from the group consisting of N-(m-dihydroxyboryl)phenyl (meth)acrylamide and derivatives thereof.

20. The method of claim 1 wherein the binding functionalities comprise a dye group and the hydrogel material is derived from dye monomers selected from the group consisting of N-(N′

-dye coupled aminopropyl) (meth)acrylamide and derivatives thereof.

21. The method of claim 1 wherein the binding functionalities comprise a cholesterol group and the hydrogel material is derived from cholesterol monomers selected from the group consisting of N-cholesteryl-3-(meth)acrylamidopropylamine and derivatives thereof.

22. The method of claim 1 wherein the surface of the substrate is conditioned with a silane-based coupling agent and the hydrogel material adheres to the surface through a covalent interaction with the coupling agent.

23. The method of claim 1 further comprising, after step (b), washing the hydrogel to remove unbound material.

24. The method of claim 1 wherein the analyte comprises a polypeptide.

25. The method of claim 1 wherein the analyte is selected from the group consisting of polynucleotides, avidin, streptavidin, polysaccharides, lectins, proteins, pepstatin, protein A, agglutinin, heparin, protein G, and concanavalin.

26. The method of claim 1 wherein the sample is selected from a cell lysate or homogenate, a tissue lysate or homogenate, an organ lysate or homogenate, blood, urine and cerebrospinal fluid.

27. The method of claim 1 wherein mass spectrometry is time-of-flight mass spectrometry.

28. The method of claim 1 wherein the substrate comprises a metal having a thickness of at least 0.5 mm, wherein the substrate is coated with silicon oxide.

29. The method of claim 1 wherein the ionization source is a laser.

30. The method of claim 29 further comprising, after step (b), applying a matrix material to the hydrogel material.

31. The method of any of claims 1–

30 wherein the substrate comprises a metal having a thickness of at least 0.5 mm.