Polynucleotide array fabrication

• US 20040203138A1
• Filed: 04/27/2004
• Published: 10/14/2004
• Est. Priority Date: 04/30/1999
• Status: Abandoned Application

• Current Assignee: Herbert F. Cattell, Jay K. Bass, Michael P. Caren, Peter G. Webb, Richard P. Tella
• Original Assignee: Herbert F. Cattell, Jay K. Bass, Michael P. Caren, Peter G. Webb, Richard P. Tella
• Inventors: Caren, Michael P., Tella, Richard P., Bass, Jay K., Webb, Peter G., Cattell, Herbert F.
• Application Number:
  US10/833,607
• Publication Number:
  US 20040203138A1
• Time in Patent Office: Days
• US Class Current: 435/287.2
• 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 2219/0036 Nozzles
• CPC Class Codes: B01J 2219/00378 Piezoelectric or ink jet dispensers
• CPC Class Codes: B01J 2219/00527 Sheets
• CPC Class Codes: B01J 2219/00529 DNA chips
• CPC Class Codes: B01J 2219/0054 Means for coding or tagging the apparatus or the reagents
• 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 2219/00608 DNA chips
• CPC Class Codes: B01J 2219/0061 The surface being organic
• CPC Class Codes: B01J 2219/00612 the surface being inorganic
• CPC Class Codes: B01J 2219/00619 using hydrophilic or hydrophobic regions
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00677 Ex-situ synthesis followed by deposition on the substrate
• CPC Class Codes: B01J 2219/00689 using computers
• CPC Class Codes: B01J 2219/00693 Means for quality control
• CPC Class Codes: B01J 2219/00695 Synthesis control routines, e.g. using computer programs
• CPC Class Codes: B01J 2219/00702 Processes involving means for analysing and characterising the products
• CPC Class Codes: B01J 2219/00722 : Nucleotides
• CPC Class Codes: B01J 2219/00725 : Peptides
• CPC Class Codes: B01L 3/0241 : Drop counters; Drop formers making arrays for combinatorial libraries B01J19/0046; automation of dispensing for analysis G01N35/10
• CPC Class Codes: B82Y 30/00 : Nanotechnology for materials or surface science, e.g. nanocomposites
• 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: C40B 70/00 : Tags or labels specially adapted for combinatorial chemistry or libraries, e.g. fluorescent tags or bar codes
• CPC Class Codes: G06T 7/0012 : Biomedical image inspection

Abstract

A method and apparatus for fabricating an array of polynucleotides on a substrate. A polynucleotide deposition system is operated to deposit an array of polynucleotide containing fluid droplets on the substrate and which, when dry, will yield polynucleotide containing spots of respective target locations and dimensions. Droplets deposited by the system are allowed to dry to yield actual spots. An image is captured of the substrate with dried actual spots. Dried actual spot locations or dimensions from the image, are compared with target locations or dimensions of polynucleotide containing spots. A signal indicative of the result of the comparison may be generated.

Claims

1. A method of fabricating an array of biopolymers on a substrate, comprising:

(a) operating a deposition system to deposit fluids on the substrate in accordance with a target pattern to produce an actual pattern of deposited fluid droplets on said substrate, which fluids contain the biopolymers or biopolymer precursors;

(b) capturing an image of the actual pattern of the deposited fluids; and

(c) comparing the actual pattern with the target pattern.

2. A method according to claim 1, wherein the image of the actual pattern is captured before the deposited fluids dry.

3. A method according to claim 1, wherein the image of the actual pattern is captured after the deposited fluids dry.

4. A method according to claim 1, wherein the deposited droplets contain polynucleotides or precursors thereof.

5. A method according to claim 1, wherein the deposited droplets contain an amino acid containing polymer or precursors thereof.

6. A method according to claim 1, wherein the deposition system comprises a pin drop dispenser.

7. A method according to claim 1, wherein the deposition system comprises a capillary drop dispenser.

8. A method according to claim 1, wherein the deposition system comprises a pulse-jet drop dispenser.

9. A method according to claim 8, wherein said pulse-jet drop dispenser comprises a heating element.

10. A method according to claim 8, wherein said pulse-jet drop dispenser comprises a piezoelectric element.

11. A method according to claim 1, wherein the comparison includes a comparison of actual spot locations or dimensions with target locations or dimensions.

12. A method according to claim 1, additionally comprising generating a signal indicative of the result of the comparison.

13. A method according to claim 1, additionally comprising:

generating an error indication based on the comparison.

14. A method according to claim 13, wherein the deposition system is operated to fabricate multiple polynucleotide arrays, the method additionally comprising rejecting the array associated with an error indication or correcting a cause of the error.

15. A method according to claim 13, additionally comprising:

writing the error indication or an identification of the error indication, on a medium; and

physically associating the medium with the array;

wherein when an identification of the error indication is written on the medium, the method further comprising storing the identification in a memory in association with the error indication.

16. A method according to claim 13, wherein the polynucleotide deposition system includes a fluid dispensing head with multiple drop dispensers, the method additionally comprising:

when multiple error conditions are generated, evaluating if a same drop dispenser is responsible; and

when the evaluation indicates the same drop dispenser is responsible, generating a visible or audible operator alert which includes an indication of the responsible drop dispenser or altering the drop deposition pattern such that the responsible drop dispenser is not used.

17. A method according to claim 1, wherein the target and actual patterns are for a test print deposited prior to fabrication of the array.

18. A method according to claim 1, wherein the target and actual patterns are for the array.

19. A method of fabricating an array of biopolymers on a substrate, comprising:

(a) operating a deposition system to deposit fluid droplets on the substrate in accordance with a target pattern to produce an actual pattern of deposited fluid droplets on said substrate, which droplets contain the biopolymers or biopolymer precursors;

(b) capturing an image of the actual pattern of the deposited droplets; and

(c) saving the actual pattern in a memory.

20. A method according to claim 19, wherein the image of the actual pattern is captured before the deposited fluids dry.

21. A method according to claim 19, wherein the image of the actual pattern is captured after the deposited fluids dry.

22. A method according to claim 19, wherein the deposited droplets contain polynucleotides or precursors thereof.

23. A method according to claim 19, wherein the deposited droplets contain an amino acid containing polymer or precursors thereof.

24. A method according to claim 19, wherein the deposition system comprises a pin drop dispenser.

25. A method according to claim 19, wherein the deposition system comprises a capillary drop dispenser.

26. A method according to claim 19, wherein the deposition system comprises a pulse-jet drop dispenser.

27. A method according to claim 26, wherein said pulse-jet drop dispenser comprises a heating element.

28. A method according to claim 26, wherein said pulse-jet drop dispenser comprises a piezoelectric element.

29. A method according to claim 19, additionally comprising saving an identification in the memory in association with the actual pattern.

30. A method according to claim 29, additionally comprising writing the identification on a medium and physically associating that medium with the array.

31. A method according to claim 30, wherein the identification is attached to the substrate.

32. A method according to claim 29 additionally comprising communicating the actual pattern in response to receiving the identification.

33. A method according to claim 19, wherein the memory comprises a portable storage medium which is sent to a user with the array.

34. A method according to claim 33, wherein the portable storage medium is sent in a same package with the array.

35. A method according to claim 34, additionally comprising writing the identification on the portable storage medium.

36. A method of fabricating an array of biopolymers on a substrate, comprising:

(a) operating a deposition system to deposit fluid droplets on the substrate in accordance with a target pattern to produce an actual pattern of deposited fluid droplets on said substrate, which droplets contain the biopolymers or biopolymer precursors;

(b) capturing an image of the actual pattern;

(c) comparing the actual pattern with the target pattern;

(e) when the results of one or more comparisons for an array exceed a predetermined tolerance, generating an error indication associated with the array; and

(f) writing the error indication or an identification of the error indication, on a medium; and

(g) physically associating the medium with the array;

wherein when an identification of the error indication is written on the medium, the method further comprising storing the identification in the memory in association with the error indication.

37. A method according to claim 36, wherein the image of the actual pattern is captured before the deposited fluids dry.

38. A method according to claim 36, wherein the image of the actual pattern is captured after the deposited fluids dry.

39. A method according to claim 36, wherein the deposited droplets contain polynucleotides or precursors thereof.

40. A method according to claim 36, wherein the deposited droplets contain an amino acid containing polymer or precursors thereof.

41. A method according to claim 36, wherein the deposition system comprises a pin drop dispenser.

42. A method according to claim 36, wherein the deposition system comprises a capillary drop dispenser.

43. A method according to claim 36, wherein the deposition system comprises a pulse-jet drop dispenser.

44. A method according to claim 43, wherein said pulse-jet drop dispenser comprises a heating element.

45. A method according to claim 43, wherein said pulse-jet drop dispenser comprises a piezoelectric element.

46. A method according to claim 36, wherein the identification is attached to the substrate.

47. A method according to claim 36, additionally comprising communicating the actual pattern in response to receiving the identification.

48. A method according to claim 36, wherein the memory comprises a portable storage medium which is sent to a user with the array.

49. A method according to claim 48, wherein the portable storage medium is sent in a same package with the array.

50. A method according to claim 49, additionally comprising writing the identification on the portable storage medium.