Matrix-assisted laser desorption ionization mass spectrometry substrates having low volume matrix array elements

• US 7,390,672 B2
• Filed: 06/18/2007
• Issued: 06/24/2008
• Est. Priority Date: 01/23/1997
• Status: Expired due to Fees

• Current Assignee: Agena Bioscience Inc. (Mesa Laboratories Inc.)
• Original Assignee: Sequenom Incorporated (Laboratory Corporation Of America Holdings)
• Inventors: O'Donnell-Maloney, Maryanne J., Köster, Hubert, Little, Daniel P., Cantor, Charles R.
• Primary Examiner(s): Gakh; Yelena G.
• Application Number:
  US11/764,711
• Publication Number:
  US 20080008874A1
• Time in Patent Office: 372 Days
• Field of Search: None
• US Class Current: 436/173
• CPC Class Codes: B01J 19/0046 Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays synthesis methods per se C40B50/00
• CPC Class Codes: B01J 2219/00315 Microtiter plates
• CPC Class Codes: B01J 2219/00317 Microwell devices, i.e. having large numbers of wells
• CPC Class Codes: B01J 2219/00378 Piezoelectric or ink jet dispensers
• CPC Class Codes: B01J 2219/00387 Applications using probes
• CPC Class Codes: B01J 2219/00468 by manipulation of individual beads
• CPC Class Codes: B01J 2219/00497 Features relating to the solid phase supports
• CPC Class Codes: B01J 2219/005 Beads
• CPC Class Codes: B01J 2219/00504 Pins
• CPC Class Codes: B01J 2219/00511 Walls of reactor vessels
• CPC Class Codes: B01J 2219/0052 in the shape of elongated tubes
• CPC Class Codes: B01J 2219/00527 Sheets
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/00596 Solid-phase processes
• CPC Class Codes: B01J 2219/00605 the compounds being directly bound or immobilised to solid supports
• CPC Class Codes: B01J 2219/0061 The surface being organic
• CPC Class Codes: B01J 2219/00612 the surface being inorganic
• CPC Class Codes: B01J 2219/00621 by physical means, e.g. trenches, raised areas
• CPC Class Codes: B01J 2219/00637 by coating it with another layer
• CPC Class Codes: B01J 2219/00641 the porous medium being continuous, e.g. porous oxide substrates
• CPC Class Codes: B01J 2219/00648 : by the use of solid beads
• CPC Class Codes: B01J 2219/00659 : Two-dimensional arrays
• CPC Class Codes: B01J 2219/0072 : Organic compounds
• CPC Class Codes: B01J 2219/00722 : Nucleotides
• CPC Class Codes: B01J 2219/00725 : Peptides
• CPC Class Codes: B01L 3/0244 : using pins
• CPC Class Codes: B01L 3/0262 : using touch-off at substrate or container
• CPC Class Codes: B01L 3/0268 : using pulse dispensing or spraying, eg. inkjet type, piezo actuated ejection of droplets from capillaries
• CPC Class Codes: C07B 2200/11 : Compounds covalently bound to a solid support
• CPC Class Codes: C07F 9/2408 : of hydroxyalkyl compounds
• CPC Class Codes: C07F 9/2429 : of arylalkanols
• CPC Class Codes: C07H 21/00 : Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
• CPC Class Codes: C40B 40/06 : Libraries containing nucleotides or polynucleotides, or derivatives thereof
• CPC Class Codes: C40B 40/10 : Libraries containing peptides or polypeptides, or derivatives thereof
• CPC Class Codes: C40B 60/14 : for creating libraries
• CPC Class Codes: G01N 2035/1037 : Using surface tension, e.g. pins or wires
• CPC Class Codes: G01N 2035/1069 : by adjusting the spacing between multiple probes of a single transferring head
• CPC Class Codes: G01N 35/1067 : for transfer to or from containers having different spacing
• CPC Class Codes: G01N 35/1074 : arranged in a two-dimensional array
• 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: Y10T 428/26 : Web or sheet containing structurally defined element or component, the element or component having a specified physical dimension
• CPC Class Codes: Y10T 428/31678 : Of metal
• CPC Class Codes: Y10T 428/31855 : Of addition polymer from unsaturated monomers
• CPC Class Codes: Y10T 436/119163 : with aspirator of claimed structure
• CPC Class Codes: Y10T 436/24 : Nuclear magnetic resonance, electron spin resonance or other spin effects or mass spectrometry
• CPC Class Codes: Y10T 436/25 : including sample preparation
• CPC Class Codes: Y10T 436/2575 : Volumetric liquid transfer

Abstract

Provided herein are substrates for matrix-assisted laser-desorption ionization (MALDI) mass spectrometric analysis. Each spot includes 3-hydroxypicolinic acid matrix and no analyte.

Claims

1. A substrate for matrix-assisted laser-desorption ionization (MALDI) mass spectrometric analysis, which comprises a surface having an array of spots, wherein each spot:

comprises 3-hydroxypicolinic acid matrix and no analyte, and

has an amount of the matrix resulting from deposition of a reproduced, defined and controlled 0.2 to 20 nanoliter volume of a solution comprising the matrix and an evaporating solvent.

2. The substrate of claim 1, wherein the substrate comprises a flat surface, a flat surface with pits or a membrane.

3. The substrate of claim 2, wherein the substrate comprises a membrane.

4. The substrate of claim 1, wherein the substrate comprises material selected from the group consisting of silica, glass, cellulose, silicon, metal, plastic, polymer and metal-grafted polymer.

5. The substrate of claim 4, wherein the substrate comprises silicon.

6. The substrate of claim 5, which is a flat silicon wafer.

7. The substrate of claim 6, wherein the silicon wafer comprises pits.

8. The substrate of claim 6, wherein the spots are about 2.25 millimeters apart.

9. The substrate of claim 6, wherein the spots are about 1.125 millimeters apart.

10. The substrate of claim 6, wherein the silicon wafer comprises a hydrophilic flat surface.

11. The substrate of claim 4, wherein the substrate comprises a metal.

12. The substrate of claim 4, wherein the substrate comprises a plastic.

13. The substrate of claim 1, wherein the substrate comprises a metal-grafted polymer.

14. The substrate of claim 1, wherein the substrate is chemically functionalized.

15. The substrate of claim 14, wherein the substrate is chemically functionalized with beads.

16. The substrate of claim 14, wherein the substrate is chemically functionalized with a dendritic material.

17. The substrate of claim 1, wherein the solution consists essentially of the matrix and the evaporating solvent.

18. The substrate of claim 1, wherein the solution consists of the matrix and the evaporating solvent.

19. The substrate of claim 1, wherein the evaporating solvent is CH₃ CN.

20. The substrate of claim 1, wherein each spot is a flat disk.

21. The substrate of claim 1, wherein the amount of matrix is reproducible from spot to spot.

22. The substrate of claim 1, wherein each spot consists essentially of matrix.

23. The substrate of claim 1, wherein each spot consists of matrix.

24. A substrate for matrix-assisted laser-desorption ionization (MALDI) mass spectrometric analysis, which comprises a surface having an array of spots, wherein

each spot comprises 3-hydroxypicolinic acid matrix resulting from the deposition of a reproduced, defined and controlled nanoliter scale volume and no analyte;

the substrate is a flat silicon chip; and

the center of each spot is about 2.25 millimeters or less from the center of an adjacent spot.

25. The substrate of claim 24, wherein each spot consists essentially of matrix.

26. The substrate of claim 24, wherein each spot consists of matrix.

27. The substrate of claim 24, wherein the silicon wafer comprises pits.

28. The substrate of claim 24, wherein the center of each spot is about 2.25 millimeters from the center of an adjacent spot.

29. The substrate of claim 24, wherein the center of each spot is about 1.125 millimeters or less from the center of an adjacent spot.

30. The substrate of claim 29, wherein the center of each spot is about 1.125 millimeters from the center of an adjacent spot.

31. The substrate of claim 29, wherein the center of each spot is about 0.5 millimeters from the center of an adjacent spot.

32. The substrate of claim 24, which comprises a hydrophilic flat surface.