Liquid delivery apparatus and method

• US 20090124519A1
• Filed: 10/03/2008
• Published: 05/14/2009
• Est. Priority Date: 08/10/2001
• Status: Abandoned Application

• Current Assignee: Oxford Genome Sciences (Uk) Limited
• Original Assignee: Oxford Genome Sciences (Uk) Limited
• Inventors: Platt, Albert Edward, Townsend, Robert Reid
• Application Number:
  US12/287,042
• Publication Number:
  US 20090124519A1
• Time in Patent Office: Days
• US Class Current: 506/30
• CPC Class Codes: B01J 2219/00367 capillary
• CPC Class Codes: B01J 2219/00369 in multiple or parallel arrangements
• CPC Class Codes: B01J 2219/00378 Piezoelectric or ink jet dispensers
• CPC Class Codes: B01J 2219/00547 Bar codes
• 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 2219/00612 the surface being inorganic
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00702 Processes involving means for analysing and characterising the products
• CPC Class Codes: B01J 2219/00725 Peptides
• CPC Class Codes: B01J 2219/00727 Glycopeptides
• CPC Class Codes: B01J 2219/00729 Peptide nucleic acids [PNA]
• 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: C40B 70/00 Tags or labels specially adapted for combinatorial chemistry or libraries, e.g. fluorescent tags or bar codes
• CPC Class Codes: G01N 35/109 with two horizontal degrees of freedom

Abstract

Liquid delivery apparatus and methods, in particular for the production of high-density arrays, wherein a partial drop of liquid is deposited from a capillary (1) onto a substrate (12), the capillary (1) and substrate (12) being capable of x, y and z movements relative to one another under the control of a translation mechanism.

Claims

1. A method for delivering a spot of liquid onto a substrate comprising:

(a) connecting a hollow capillary to the liquid outlet of a sample separator;

(b) locating the capillary above a selected position on the substrate;

(c) delivering a partial drop of liquid from the capillary onto the substrate by relative movement of the capillary and substrate;

(d) retraction of the capillary and substrate relative to each other; and

(e) repeating steps (c) and (d) one or more times.

2. The method of claim 1, wherein the delivery of sample is achieved by movement of the capillary towards the substrate followed by retraction of said capillary.

3. The method of claim 1, wherein a plurality of discrete partial drops of liquid are applied to the same position on the substrate.

4. The method of claim 3 wherein the spot of liquid on the substrate is partially dried between each deposition of a partial drop of liquid.

5. The method of claim 3, wherein the retraction of the capillary relative to the substrate is greater each time, to a degree dependent on the flow rate of the liquid through the capillary and the height of the spot of liquid on the substrate.

6. The method of claim 1, wherein said retraction of the capillary is such as to maintain the contact of the partial drop of liquid with both the capillary and the substrate, the relative movement of the capillary and substrate being controlled to maintain a column of liquid between the substrate and the capillary of a pre-determined width.

7. The method according to claim 1, wherein the diameter of the partial drop formed on the end of the capillary is no greater than the diameter of the capillary.

12. The method according to claim 1, wherein the diameter of each spot is less than 750 μ

m.

13. The apparatus or method according to claim 1, wherein the diameter of each spot is between 100 μ

m and 500 μ

m.

14. A method of application of a matrix material, suitable for MALDI mass spectrometry, in one or more aliquots to a plurality of sample spots, said spots being generated according to the method of claim 1, comprising non-contact delivery of said matrix material from a second delivery device.

15. The method of claim 14, wherein the matrix material is delivered onto the sample spots before said spots have dried.

16. The method according to claim 14, wherein the second delivery device is washed and/or dried at least once during the generation of an array of sample spots

17. A method according to claim 1, comprising using a computer comprising a computer-readable medium with program instructions, for generating machine-readable instructions that direct a liquid delivery apparatus according to any one of claims 7 to 9, to commence producing an array of spots of sample on a substrate.

18. A method according to claim 1, comprising using a computer comprising a computer-readable medium having a program recorded thereon, where the program instructs the computer execute procedure to perform the following steps:

(a) generate instructions that direct a device comprising a sample separator to commence delivery of liquid;

(b) generate instructions that direct a liquid delivery apparatus according to any one of claims 7 to 9, to commence delivering a plurality of spots of said liquid, wherein the device of part (a) is interfaced to a capillary of the liquid delivery apparatus; and

(c) generate instructions that direct the liquid delivery apparatus of part (b) to deliver matrix material according to any one of claims 14 to 16.

19. A method according to claim 1, wherein the liquid is derived from the separations of samples that have been labelled with undeuterated or D₈-isotope-coded affinity tags or alternatively with undeuterated or D₇-isotope labelled tags.

20. A method according to claim 1 for the production of a plurality of spatially distinct spots of sample on a substrate for analysis.

21. The method according to claim 20, wherein the sample comprises peptides and the analysis comprises mass spectrometry.

8. A liquid delivery apparatus comprising:

(a) at least one hollow capillary adapted for connection to the liquid outlet of a sample separator;

(b) a housing to retain said capillary in a desired orientation;

(c) one or more thermal, mechanical or electrical second liquid delivery devices;

(d) a housing to retain said second liquid delivery device in a desired orientation;

(d) a substrate holder; and

(e) a translation mechanism capable of performing x, y and z movements, said mechanism being capable of moving said capillary, second liquid delivery device and substrate holder relative to one another.

9. The liquid delivery apparatus of claim 8, further comprising a means of controlling the evaporation rate of the deposited drop of liquid.

10. The liquid delivery apparatus of claim 8, which comprises means to measure the volume of liquid deposited upon a substrate.

11. The liquid delivery apparatus of claim 8, wherein the capillary is coated or surface treated with a non-wetting agent.

22. A method for producing an array of peptides for mass spectrometric analysis on a solid substrate comprising:

(a) connecting a hollow capillary to the liquid outlet of a sample separator wherein the liquid sample contains polypeptides;

(b) locating the capillary above a selected position on the substrate;

(c) delivering a partial drop of liquid from the capillary onto the substrate by relative movement of the capillary and substrate;

(d) retraction of the capillary and substrate relative to each other

(e) repeating steps (c) and (d) one or more times;

(f) relocating the capillary above a different selected position on the substrate and performing steps (c) to (e);

(g) repeating step (f) one or more times; and

(h) applying a matrix solution to the spots of liquid on the substrate before the liquid has completely evaporated.