Biopolymer array fabrication using different drop deposition heads

• US 20040219663A1
• Filed: 04/30/2003
• Published: 11/04/2004
• Est. Priority Date: 04/30/2003
• Status: Abandoned Application

• Current Assignee: Agilent Technologies, Inc.
• Original Assignee: Agilent Technologies, Inc.
• Inventors: Scalia, John P., Page, Robert D., Leproust, Eric M.
• Application Number:
  US10/427,764
• Publication Number:
  US 20040219663A1
• 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 2219/0036 Nozzles
• CPC Class Codes: B01J 2219/00378 Piezoelectric or ink jet dispensers
• CPC Class Codes: B01J 2219/0054 Means for coding or tagging the apparatus or the reagents
• CPC Class Codes: B01J 2219/00547 Bar codes
• CPC Class Codes: B01J 2219/00563 Magnetic means
• 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 2219/00626 Covalent
• 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 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00689 using computers
• CPC Class Codes: B01J 2219/00695 Synthesis control routines, e.g. using computer programs
• CPC Class Codes: B01J 2219/00722 Nucleotides
• CPC Class Codes: B01J 2219/00725 Peptides

Abstract

A method of fabricating an array of biopolymer probes bound to a surface of a substrate at feature locations. The method uses multiple deposition heads each with a set of nozzles through which drops are dispensed. Drops are deposited during a same cycle onto the feature location from a set of the deposition heads while spaced from the surface. At least some of those drops contain probe precursors, so that the probe precursors bind to the surface through a linker. This depositing is repeated multiple times with the probe precursor deposited in a prior cycle serving as the linker for a probe precursor deposited in a subsequent cycle. Additionally, drops are deposited at a same feature from the set of heads during a one cycle, and further drops are deposited at the same feature from the set of heads during another cycle. Apparatus and computer program products are also provided.

Claims

1. A method of fabricating an array of biopolymer probes bound to a surface of a substrate at feature locations, using deposition heads each comprising a set of fixed nozzles through which drops are dispensed, the method comprising for each of multiple feature locations:

(a) depositing drops during a same cycle onto the feature location from a set of the deposition heads while spaced from the surface, at least some of which drops contain probe precursors, so that the probe precursors bind to the surface through a linker;

(b) repeating (a) multiple times wherein the probe precursor deposited in a prior cycle becomes the linker for a probe precursor deposited in a subsequent cycle;

wherein drops are deposited at a same feature from the set of heads during a one cycle, and further drops are deposited at the same feature from the set of heads during another cycle.

2. A method according to claim 1 wherein the biopolymer probes comprise polynucleotide or peptide probes.

3. A method according to claim 2 wherein:

the set of heads comprises a first head and a second head;

the drops deposited at the same feature from the set of heads during the one cycle comprise a drop of a probe precursor from the first head and a drop of an activator from the second head; and

the drops deposited at the same feature in the other cycle comprise a drop of a probe precursor from the second head and a drop of the activator from the first head.

4. A method according to claim 3 wherein the probe precursor deposited at the same feature in the one cycle is different from the probe precursor deposited during the other cycle.

5. A method according to claim 2 wherein:

the set of heads comprises a first head and a second head;

the drops deposited at the same feature from the set of heads during the one cycle comprise a series of drops of the probe precursor from the first head and a series of drops of an activator from the second head; and

the drops deposited at the same feature in the other cycle comprise a series of drops of the probe precursor from the second head and a series of drops of the activator from the first head.

6. A method according to claim 3 wherein all the drops deposited at the same feature location from the different heads during a same cycle together cover an area on the surface which is substantially coextensive over different cycles.

7. A method according to claim 6 wherein all the drops deposited at the same feature location from a same head during a same cycle together have an area of coverage which is substantially constant across different heads and different cycles.

8. A method according to claim 6 wherein:

the set of heads comprises a first head and a second head;

the drops deposited at the same feature from the set of heads during a same cycle comprise a drop of a probe precursor from the first head and a drop of an activator from the first head and from the second head.

9. A method according to claim 6 wherein:

the set of heads comprises a first head and a second head;

the drops deposited at the same feature from the set of heads during the one cycle comprise a drop of a probe precursor from the first head and a drop of an activator from the first head and from the second head; and

the drops deposited at the same feature in the other cycle comprise a drop of a probe precursor from the second head and a drop of the activator from the first head and from the second head.

10. A method according to claim 9 wherein the activator deposited from the first and second heads at the same feature during each of the cycles has a coverage area which is greater than the probe precursor deposited during the same cycle.

11. A method according to claim 5 wherein the drops within each series at the same feature are displaced relative to one another along a first direction while series from different heads are displaced relative to one another in a direction crosswise to the first direction.

12. A method according to claim 6 wherein drops of an activator and probe precursor are dispensed from the first and second heads, with different probe precursors being dispensed from the first and second heads.

13. A method according to claim 12 wherein the biopolymer probe comprises polynucleotides and wherein an activator and a pair of nucleoside monomers are dispensed from each of the first and second heads, with different pairs of nucleoside monomers being dispensed from the first and second heads.

14. A method according to claim 12 wherein the same activator is dispensed from the different heads.

15. A method according to claim 6 additionally comprising exposing the fabricated array to a sample.

16. A method according to claim 15 additionally comprising, following exposure of the array to a sample, reading the array.

17. A method comprising forwarding a result of a reading obtained by the method of claim 16, to a remote location.

18. A method comprising receiving a result of reading obtained by the method of claim 16 from a remote location.

19. A method according to claim 1 wherein the probes comprise polynucleotide probes and the probe precursors comprise nucleoside phosphoramidites.

20. A method according to claim 3 wherein the probes comprise polynucleotide probes and the probe precursors comprise nucleoside phosphoramidites.

21. A method according to claim 6 wherein the probes comprise polynucleotide probes and the probe precursors comprise nucleoside phosphoramidites.

22. A method according to claim 1 wherein the set of nozzles of a head are formed in a one-piece member.

23. A computer program product, comprising:

a computer readable storage medium having a computer program stored thereon which executes a method of claim 1 when loaded into a computer.

24. A computer program product, comprising:

a computer readable storage medium having a computer program stored thereon which executes a method of claim 3 when loaded into a computer.

25. A computer program product, comprising:

a computer readable storage medium having a computer program stored thereon which executes a method of claim 6 when loaded into a computer.

26. A computer program product, comprising:

a computer readable storage medium having a computer program stored thereon which executes a method of claim 8 when loaded into a computer.

27. An array fabrication apparatus comprising:

multiple deposition heads each comprising multiple fixed nozzles through which drops are dispensed;

a processor which controls operation of the deposition heads so as to execute a method of claim 1.

28. An array fabrication apparatus comprising:

multiple deposition heads each comprising multiple fixed nozzles through which drops are dispensed;

a processor which controls operation of the deposition heads so as to execute a method of claim 3.

29. An array fabrication apparatus comprising:

multiple deposition heads each comprising multiple fixed nozzles through which drops are dispensed;

a processor which controls operation of the deposition heads so as to execute a method of claim 6.

30. An array fabrication apparatus comprising:

multiple deposition heads each comprising multiple fixed nozzles through which drops are dispensed;

a processor which controls operation of the deposition heads so as to execute a method of claim 8.

31. A method according to claim 30 wherein the set of nozzles of a head are formed in a one-piece member.

37. A method according to claim 1 wherein the set of nozzles of a head are formed in a one-piece member.

32. A method of fabricating an array of biopolymer probes bound to a surface of a substrate at feature locations, using a set of deposition heads each comprising a set of nozzles through which drops are dispensed, the method comprising:

(a) adjusting the relative orientation of heads in the set so as to simultaneously adjust the trajectories of drops ejected from a set of nozzles of one head relative to a set of nozzles of another head;

(b) fabricating an array comprising, for each of multiple feature locations;

(i) depositing drops during a same cycle onto the feature location from a set of the deposition heads while spaced from the surface, at least some of which drops contain probe precursors, so that the probe precursors bind to the surface through a linker;

(ii) repeating (i) multiple times wherein the probe precursor deposited in a prior cycle becomes the linker for a probe precursor deposited in a subsequent cycle;

wherein drops are deposited at a same feature from the set of heads during a one cycle, and further drops are deposited at the same feature from the set of heads during another cycle.

33. A method according to claim 32 wherein the probes comprise polynucleotide probes.

34. A method according to claim 33 wherein:

the set of heads comprises a first head and a second head;

the drops deposited at the same feature from the set of heads during the one cycle comprise a drop of a probe precursor from the first head and a drop of an activator from the second head; and

the drops deposited at the same feature in the other cycle comprise a drop of a probe precursor from the second head and a drop of the activator from the first head.

35. A method according to claim 34 wherein the probe precursor deposited at the same feature in the one cycle is different from the probe precursor deposited during the other cycle.

36. A method according to claim 32 wherein the drops deposited at the same feature location from the different heads during a cycle together cover an area on the surface which is substantially coextensive across different cycles.