Methods and devices for detecting printhead misalignment of an in situ polymeric array synthesis device

• US 7,070,932 B2
• Filed: 02/25/2003
• Issued: 07/04/2006
• Est. Priority Date: 02/25/2003
• Status: Expired due to Fees

• Current Assignee: Agilent Technologies, Inc.
• Original Assignee: Agilent Technologies, Inc.
• Inventors: Leproust, Eric M., Kronick, Mel N., Amorese, Douglas A.
• Primary Examiner(s): GOLDBERG, JEANINE ANNE
• Application Number:
  US10/374,307
• Publication Number:
  US 20040170984A1
• Time in Patent Office: 1,225 Days
• Field of Search: None
• US Class Current: 506/9
• CPC Class Codes: C12Q 1/6837 using probe arrays or probe chips C12Q1/6874 takes precedence
• CPC Class Codes: C12Q 2525/173 incorporating a polynucleotide run, e.g. polyAs, polyTs

Abstract

Methods and devices for detecting deposition unit misalignment, e.g., printhead misalignment, of an in situ polymeric, e.g., a nucleic acid, array synthesis device are provided. In accordance with the subject methods, at least one test probe feature is synthesized on a substrate using an in situ polymeric array, e.g., nucleic acid array or protein array, synthesis device. The at least one test probe feature is then contacted with at least two different distinguishably labeled targets, e.g., target nucleic acids. The binding of the targets to the at least one test probe feature is then evaluated to detect any misalignment, e.g., deposition unit or pulse jet misalignments, of the synthesis device. Also provided are substrates having at least one test probe feature and at least one polymeric array, as well as methods of using the substrates in array assays. Also included are kits for use in practicing the subject methods.

Claims

1. A method of detecting deposition unit misalignment of an in situ polymeric array synthesis device, said method comprising:

synthesizing at least one test probe feature on a substrate using said in situ polymeric array synthesis device;

contacting said at least one test probe feature with at least two different distinguishably labeled targets; and

evaluating the binding of said two different distinguishably labeled targets to said at least one test probe feature to detect any pulse jet misalignment of said in situ polymeric array synthesis device.

2. The method according to claim 1, wherein said targets preferentially bind to different polymers each formed from less than all precursor units used to synthesize the at least one test probe feature.

3. The method according to claim 2, wherein the different polymers to which the targets preferentially bind are each formed from multiple precursor units used to synthesize the at least one test probe feature.

4. The method according to claim 3, wherein the different polymers to which the targets preferentially bind are each formed from no more than half the precursor units used to synthesize the at least one test probe feature.

5. The method according to claim 2, wherein different sub-sets of the precursor units used to synthesize the at least one test probe feature are deposited from different printheads, and wherein the different polymers to which the targets preferentially bind are formed from the different sub-sets of the precursor units so that printhead misalignment is detected by the evaluating.

6. The method according to claim 5, wherein said deposition units are pulse jets.

7. A method of detecting printhead misalignment of an in situ nucleic acid array synthesis device, said method comprising:

synthesizing at least one test probe feature on a substrate using said in situ nucleic acid array synthesis device;

contacting said at least one test probe feature with at least two different distinguishably labeled target nucleic acids; and

evaluating the binding of said two different distinguishably labeled target nucleic acids to said at least one test probe feature to detect any printhead misalignment of said in situ nucleic acid array synthesis device.

8. The method according to claim 7, wherein said at least one test probe feature is made up of only two nucleotides chosen from the group of A, C, T and G.

9. The method according to claim 8, wherein said synthesizing comprises synthesizing two or more test probe features chosen from the group of A and C;

A and G;

A and T;

C and G;

C and T;

T and C; and

G and T.

10. The method according to claim 7, wherein said at least two different distinguishably labeled target nucleic acids are homopolymers.

11. The method according to claim 10, wherein said at least two different distinguishably labeled target nucleic acids comprise four different homopolymers.

12. The method according to claim 11, wherein said four different homopolymers comprise poly A, poly C, poly T and poly G.

13. The method according to claim 10, wherein at least two of said homopolymers are labeled with the same label.

14. The method according to claim 13, wherein three of said homopolymers are labeled with the same label.

15. The method according to claim 7, wherein said at least one test probe feature comprises four different nucleotides.

16. The method according to claim 15, wherein said at least two different distinguishably labeled target nucleic acids are made up of two different nucleotides chosen from the group of A and G;

A and T;

C and G;

C and T;

A and C; and

G and T.

17. The method according to claim 7, further comprising adjusting one or more printheads if misalignment is detected.

18. The method according to claim 7, further comprising synthesizing at least one nucleic acid array on a substrate using said in situ nucleic acid array synthesis device.

19. The method according to claim 18, wherein said at least one nucleic acid array synthesis occurs after adjusting one or more printheads based on said evaluating.

20. The method according to claim 18, wherein said at least one nucleic acid array is synthesized on the same substrate as said at least one test probe feature.

21. The method according to claim 7, wherein said distinguishable labels are fluorescent.

22. The method according to claim 7, wherein said evaluating comprises optically scanning said substrate surface.

23. A method of synthesizing at least one nucleic acid array using an in situ nucleic acid array synthesis device, said method comprising:

detecting any printhead misalignment of said in situ nucleic acid array synthesis device according to claim 7,

adjusting any detected printhead misalignment of said in situ nucleic acid array synthesis device; and

synthesizing at least one nucleic acid array using said in situ nucleic acid array synthesis device.

24. A method of detecting the presence of an analyte in a sample, said method comprising:

(a) contacting a sample suspected of comprising said analyte with a nucleic acid array synthesized according to claim 23;

(b) detecting any binding complexes on the surface of the said array to determine the presence of said analyte in said sample using said binding complex data.

25. The method according to claim 24, wherein said method further comprises a data transmission step in which a result from a reading of the array is transmitted from a first location to a second location.

26. The method according to claim 25, wherein said second location is a remote location.

27. A method comprising receiving data representing a result of a reading obtained by the method of claim 25.