Systems and methods for preparing and analyzing low volume analyte array elements

• US 7,232,688 B2
• Filed: 07/30/1999
• Issued: 06/19/2007
• 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: Little, Daniel P., Cantor, Charles R., Koster, Hubert, O'Donnell-Maloney, Maryanne J.
• Primary Examiner(s): Gakh; Yelena G.
• Application Number:
  US09/364,774
• Publication Number:
  US 20030096426A1
• Time in Patent Office: 2,881 Days
• Field of Search: 250/288, 250/423.R, 250/442.11, 436/47, 436/173, 436/18, 422/104
• 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

Methods for dispensing tools that can be employed to generate multi-element arrays of sample material on a substrate surface. The resulting substrates are also provided. The substrates surfaces can be flat or geometrically altered to include wells of receiving material. The tool can dispense a spot of fluid to a substrate surface by spraying the fluid from the pin, contacting the substrate surface or forming a drop that touches against the substrate surface. The tool can form an array of sample material by dispensing sample material in a series of steps, while moving the pin to different locations above the substrate surface to form the sample array. The prepared sample arrays are passed to a plate assembly that disposes the sample arrays for analysis by mass spectrometry. To this end, a mass spectrometer is provided that generates a set of spectra signals that are indicative of the composition of the sample material under analysis.

Claims

1. A substrate, comprising a surface comprising material deposited at a plurality of discrete locations thereon thereby forming an array of spots thereon, wherein:

the material comprises matrix material and a sample for matrix-assisted laser-desorption ionization (MALDI) mass spectrometric analysis;

the material in each spot is in amount that results from deposition of a defined and controlled sub-nanoliter to low-nanoliter volume of a solution containing the material;

MALDI mass spectra of the sample obtained directly from each spot are reproducible from spot to spot within the array of spots.

2. A substrate of claim 1, wherein the surface is flat.

3. A substrate of claim 1 having wells disposed on the surface, wherein the material is deposited in the wells.

4. A substrate of claim 3, wherein the wells have a rough interior surface.

5. A substrate of claim 1, wherein the surface is pitted.

6. A substrate of claim 5, that comprises pits with beads therein.

7. A substrate of claim 1, comprising an array of pins wherein the material is deposited on the end of the pin.

8. A substrate of claim 1, wherein the substrate comprises silica gel, controlled pore glass, magnetic beads, cross-linked dextrans, agarose, cellulose, glass, metal, or plastic.

9. A substrate of claim 8, wherein the metal is selected from the group consisting of steel, gold, silver aluminum and copper.

10. A substrate of claim 1, wherein the material further comprises a nucleic acid.

11. A substrate of claim 1, selected from the group consisting of capillaries, a capillary, a flat supports and membranes.

12. A substrate of claim 11, wherein the membrane comprises polyethylene, polypropylene, polyamide or polyvinylidenedifluoride.

13. A substrate of claim 1 that comprises silicon.

14. A substrate of claim 13 that is a silicon wafer.

15. The substrate of claim 13 that is a pitted silicon chip.

16. The substrate of claim 13 that comprises a hydrophilic flat surface.

17. A substrate of claim 1, wherein the surface of the substrate comprises metal, plastic, a membrane, polymeric material and a metal-grafted polymer.

18. A substrate of claim 1, wherein the surface of the substrate is functionalized chemically, functionalized with beads or functionalized with dendrite trees of captured material.

19. The substrate of claim 1, wherein the discrete locations are approximately 500 μ

m apart.

20. The substrate of claim 1 that comprises a hydrophilic flat surface.

21. A substrate of claim 1, wherein the material at each location is in an amount that results from deposition of a defined and controlled 0.2 to 20 nanoliter volume containing the material on the surface.

22. A substrate of claim 21, wherein the material further comprises a nucleic acid.

23. The substrate of claim 21 that comprises a hydrophilic flat surface.

24. The substrate of claim 23 that comprises silica gel, controlled pore glass, magnetic beads, cross-linked dextrans, agarose, cellulose, glass, metal, or plastic.

25. The substrate of claim 21 that comprises silicon.

26. The substrate of claim 25 that is a silicon wafer.

27. The substrate of claim 1, wherein the discrete locations are hydrophilic.

28. The substrate of claim 27 that comprises silica gel, controlled pore glass, magnetic beads, cross-linked dextrans, agarose, cellulose, glass, metal, or plastic.

29. The substrate of claim 27 that comprises silicon.

30. The substrate of claim 29 that is a silicon wafer.

31. The substrate of claim 27, wherein the material further comprises a nucleic acid.