Error correction in array fabrication

• US 20030143329A1
• Filed: 01/30/2002
• Published: 07/31/2003
• Est. Priority Date: 01/30/2002
• Status: Abandoned Application

• Current Assignee: Agilent Technologies, Inc.
• Original Assignee: Agilent Technologies, Inc.
• Inventors: Webb, Peter G., Fisher, William D., Shchegrova, Svetlana V.
• Application Number:
  US10/061,800
• Publication Number:
  US 20030143329A1
• Time in Patent Office: Days
• US Class Current: 427/256
• 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 2219/00378 Piezoelectric or ink jet dispensers
• CPC Class Codes: B01J 2219/00527 Sheets
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/0059 Sequential 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 2219/00637 by coating it with another layer
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• 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 2219/00722 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: 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 35/1009 : Characterised by arrangements for controlling the aspiration or dispense of liquids
• CPC Class Codes: Y10T 436/2575 : Volumetric liquid transfer

Abstract

A method, apparatus, and computer program products useful in fabricating a chemical array. The apparatus may include a head system, transport system, and a processor. The head system has multiple groups of drop dispensers. The transport system moves the head system with respect to a substrate. The processor dispenses drops from dispensers during operation of the transport system, in a pattern along a selected path for each group. The method, apparatus, and computer program products provide a means by which error dispensers can readily be replaced by redundant non-error dispensers loaded with the same fluid.

Claims

1. A method of fabricating a chemical array using:

a head system with multiple groups of drop dispensers;

a transport system to move the head system with respect to a substrate;

a processor to dispense droplets from dispensers during operation of the transport system, in a pattern along a selected path for each group;

the method comprising;

a) loading the dispensers with fluid such that each dispenser group has at least one set of redundant dispensers loaded with a same fluid;

b) dispensing drops from the dispensers to identify an error in one or more dispensers;

c) moving a first dispenser of each set in each group along the selected path for that group while dispensing drops from non-error first dispensers of the sets in at least part of the pattern along the selected path for each group;

d) moving a second dispenser of the sets in each group along the selected path for that group while dispensing drops from a non-error second dispenser of a set having an identified error first dispenser, in at least part of the pattern for the selected path of the first group; and

e) repeating (a) through (d) at least once;

wherein the array is fabricated.

2. A method according to claim 1 wherein in step (d) drops are dispensed from each second dispenser of multiple groups in at least part of the pattern for the selected path of the same group.

3. A method according to claim 2 wherein:

dispensers within a set of redundant dispensers communicate with a common reservoir for that set.

4. A method according to claim 1 wherein the dispensers are pulse jets.

5. A method according to claim 2 wherein in (d) the drops are dispensed from at least one second dispenser of a set of redundant dispensers, in the complete pattern for the first dispenser of the same set.

45. A method comprising,

reading an array from the method of claim 1, following exposure of the array to a sample.

46. A method comprising forwarding data representing a result of a reading obtained by the method of claim 45.

47. A method according to claim 46 wherein the data is communicated to a remote location.

48. A method comprising receiving data representing a result of a reading obtained by the method of claim 45.

6. A method of fabricating a chemical array using:

a head system with multiple groups of dispensers, the members of each group being arranged in multiple series extending in a first direction and multiple sets;

a transport system to move the head system with respect to a substrate with different series following respective paths, series from different groups which can simultaneously move along the selected paths for their groups forming a dispenser frame;

a processor to dispense drops from dispensers during operation of the transport system, in a pattern along a selected path for each group;

the method comprising;

a) loading the dispensers with fluid such that dispensers within each set of the groups are loaded with a same fluid;

b) dispensing drops from the dispensers to identify an error in one or more dispensers;

c) moving a first dispenser frame along the selected paths for the groups while dispensing drops from non-error dispensers of the first frame in at least part of the patterns along the selected paths for the groups;

d) when an error dispenser is detected in the first frame, moving a further frame along the selected paths for the groups while dispensing drops from a non-error dispenser of the further frame located in the same set as the error dispenser, in at least part of the patterns along the selected paths for the groups; and

e) repeating (a) through (d) at least once;

wherein the array is fabricated.

7. A method according to claim 6 wherein the multiple sets extend in a second direction sideways to the first direction

8. A method according to claim 7 wherein the selected paths extend in the first direction.

9. A method according to claim 7 wherein the dispensers of the head system move in unison.

10. A method according to claim 7 wherein the first and further dispenser frames are moved in turn along the selected paths.

11. A method according to claim 8 wherein the head is displaced sideways to the selected paths to bring each further frame into alignment with the selected paths.

12. A method according to claim 8 wherein the first frame is selected based on the number of non-error dispensers in the first frame.

13. A method according to claim 8 wherein in (d) when error dispensers are detected in a further frame, then multiple further frames are moved along the selected paths for the groups while dispensing drops from non-error dispensers of each of the further frames in at least part of the patterns along the selected paths for the groups.

14. A method according to claim 13 wherein drops are dispensed from non-error dispensers in the same sets as the error dispensers.

15. A method according to claim 8 wherein in (c) and (d) frames so moved are each selected as a frame among previously non-selected frames which has the highest number of non-error dispensers in sets not containing a non-error dispenser in a previously selected frame.

16. A method according to claim 15 wherein when more than one frame has the highest number then selecting from among such highest number frames a frame which has a best non-error dispenser in a set not containing a non-error dispenser in a previously selected frame, wherein the best non-error dispenser more closely meets a predetermined criterion than a non-error dispenser of another highest number frame.

17. A method according to claim 15 additionally comprising, when a set contains a non-error dispenser in more than one selected frame, then determining a best dispenser from among those non-error dispensers which more closely meets a predetermined criterion and dispensing drops in at least part of the pattern along the selected path for that group in which that best dispenser is located when the frame containing that best dispenser is moved along the selected path for that group.

18. A method according to claim 16 wherein the predetermined criterion is a drop size.

19. A method according to claim 16 wherein the predetermined criterion is a drop placement.

20. A method according to claim 7 wherein the dispensers are pulse jets.

21. A method according to claim 12 wherein:

dispensers in each of multiple sets of each of multiple groups, communicate with a corresponding common reservoir for that column.

22. A method according to claim 7 wherein the dispensing of (b) is performed after each loading in (a) and before the moving and dispensing of (c) and (d).

23. A method according to claim 7 wherein the series are arranged in rows.

24. A method according to claim 7 wherein the sets are arranged in columns.

25. A method of fabricating a chemical array using:

a head system with multiple groups of dispensers, the members of each group being arranged in multiple series extending in a first direction and multiple sets extending in a second direction sideways to the first direction;

a transport system to move the head system with respect to a substrate with different series following respective paths, series from different groups which can simultaneously move along the selected paths for their groups forming a dispenser frame;

a processor to dispense drops from dispensers during operation of the transport system, in a pattern along a selected path for each group;

the method comprising;

a) loading the dispensers with fluid such that dispensers within each set of the groups are loaded with a same fluid;

b) dispensing drops from the dispensers to identify an error in one or more dispensers;

c) moving a first frame along the selected paths for the groups while dispensing drops from non-error dispensers of the first frame in at least part of the patterns along the selected paths for the groups; and

d) when an error dispenser is detected in the first frame, then multiple selected frames are moved along the selected paths for the groups while dispensing drops from non-error dispensers of each of the frames in at least part of the patterns along the selected paths for the groups, wherein each of the frames so moved is selected as the frame among previously non-selected frames which has the highest number of non-error dispensers in sets not containing a non-error dispenser in a previously selected frame;

wherein the array is fabricated.

26. A method according to claim 25 wherein the selected paths extend in the first direction.

27. A method according to claim 25 wherein the dispensers of the head system move in unison.

28. A method according to claim 25 wherein the first and further dispenser frames are moved in turn along the selected paths.

29. A method according to claim 26 wherein the head is displaced sideways to the selected paths to bring each further frame into alignment with the selected paths.

30. A method according to claim 25 wherein the dispensers are pulse jets.

31. A method according to claim 25 wherein:

dispensers in each of multiple sets of each of multiple groups, communicate with a corresponding common reservoir for that column.

32. A method according to claim 25 wherein the series are arranged in rows.

33. A method according to claim 26 wherein the sets are arranged in columns.

34. An apparatus for fabricating a chemical array, comprising:

(a) a head system with multiple groups of drop dispensers, each group having multiple drop dispensers;

(b) a transport system to move the head system with respect to a substrate;

(c) a processor which;

i) loads the dispensers with fluid such that each dispenser group has at least one set of redundant dispensers loaded with a same fluid;

ii) dispenses drops from the dispensers to identify an error in one or more dispensers;

iii) moves a first dispenser of each set in each group along a selected path for that group while dispensing drops from non-error first dispensers of the sets in at least part of a pattern along the selected path for each group;

iv) moves a second dispenser of the sets in each group along the selected path for that group while dispensing drops from a non-error second dispenser of a set having an identified error first dispenser in at least part of the pattern for the selected path of the first group; and

v) repeats (i) through (iv) at least once;

such that the array is fabricated.

35. An apparatus according to claim 34 wherein the dispensers are pulse jets.

36. An apparatus according to claim 35 wherein:

dispensers in each of multiple sets of each of multiple groups, communicate with a corresponding common reservoir for that set.

37. An apparatus for fabricating a chemical array, comprising:

(a) a head system with multiple groups of dispensers, the members of each group being arranged in multiple series extending in a first direction and in multiple sets extending sideways to the first direction;

(b) a transport system to move the head system with respect to a substrate with different series following respective paths, series from different groups which can simultaneously move along the selected paths for their groups forming a dispenser frame;

(c) a processor;

which;

i) loads the dispensers with fluid such that dispensers within each set of the groups are loaded with a same fluid;

ii) dispenses drops from the dispensers to identify an error in one or more dispensers;

iii) moves a first dispenser frame along the selected paths for the groups while dispensing drops from non-error dispensers of the first frame in at least part of the patterns along the selected paths for the groups;

iv) when an error dispenser is detected in the first frame, moves a further frame along the selected paths for the groups while dispensing drops from a non-error dispenser of the further frame located in the same column as the error dispenser, in at least part of the patterns along the selected paths for the groups;

v) repeats (i) through (iv) at least once;

such that the array is fabricated.

38. An apparatus according to claim 37 wherein the dispensers are pulse jets.

39. An apparatus according to claim 37 wherein:

dispensers in each of multiple sets of each of multiple groups, communicate with a corresponding common reservoir for that set.

40. An apparatus according to claim 37 wherein the series are arranged in rows and the sets in columns.

41. A computer program product for use with a chemical array fabricating apparatus having:

a head system with multiple groups of drop dispensers, each group having multiple drop dispensers;

a transport system to move the head system with respect to a substrate; and

a processor;

the computer program product comprising a computer readable storage medium having a computer program stored thereon which, when loaded into the processor, performs;

i) loading the dispensers with fluid such that each dispenser group has at least one set of redundant dispensers loaded with a same fluid;

ii) dispensing drops from the dispensers to identify an error in one or more dispensers;

iii) moving a first dispenser of each set in each group along a selected path for that group while dispensing drops from non-error first dispensers of the sets in at least part of a pattern along the selected path for each group;

iv) moving a second dispenser of the sets in each group along the selected path for that group while dispensing drops from a non-error second dispenser of a set having an identified error first dispenser in at least part of the pattern for the selected path of the first group; and

v) repeating (i) through (iv) at least once;

such that the array is fabricated.

42. A computer program product according to claim 41 wherein the program moves the first and further dispenser frames in turn along the selected paths.

43. A computer program product according to claim 42 wherein the displaces the head system sideways to the selected paths to bring each further frame into alignment with the selected paths.

44. A computer program product for use with a chemical array fabricating apparatus having:

a head system with multiple groups of dispensers, the members of each group being arranged in multiple series extending in a first direction and in multiple sets extending sideways to the first direction;

a transport system to move the head system with respect to a substrate with different series following respective paths, series from different groups which can simultaneously move along the selected paths for their groups forming a dispenser frame; and

a processor;

the computer program product comprising a computer readable storage medium having a computer program stored thereon which, when loaded into the processor, performs;

i) loading the dispensers with fluid such that dispensers within each set of the groups are loaded with a same fluid;

ii) dispensing drops from the dispensers to identify an error in one or more dispensers;

iii) moving a first dispenser frame along the selected paths for the groups while dispensing drops from non-error dispensers of the first frame in at least part of the patterns along the selected paths for the groups;

iv) when an error dispenser is detected in the first frame, moving a further frame along the selected paths for the groups while dispensing drops from a non-error dispenser of the further frame located in the same column as the error dispenser, in at least part of the patterns along the selected paths for the groups;

v) repeating (i) through (iv) at least once;

such that the array is fabricated.