Methods of fabricating an addressable array of biopolymer probes

• US 7,276,336 B1
• Filed: 07/22/1999
• Issued: 10/02/2007
• Est. Priority Date: 07/22/1999
• Status: Expired due to Fees

• Current Assignee: Agilent Technologies, Inc.
• Original Assignee: Agilent Technologies, Inc.
• Inventors: Caren, Michael P., Bass, Jay K., Webb, Peter G., Schleifer, Kyle J.
• Primary Examiner(s): FORMAN, BETTY J
• Application Number:
  US09/359,527
• Time in Patent Office: 2,994 Days
• Field of Search: 435/6, 536/23.1
• US Class Current: 435/6.19
• 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 2219/00626 Covalent
• 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 2219/00677 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 of fabricating an addressable array of biopolymer probes on a substrate according to a target array pattern using a deposition apparatus, and a deposition apparatus which can execute the method and computer program products for the apparatus. The deposition apparatus which, when operated according to a target drive pattern based on nominal operating parameters of the apparatus, provides the probes on the substrate in the target array pattern. The method includes examining at least one operating parameter for an error from a nominal value which error will result in use of the target drive pattern producing a discrepancy between the target array pattern and an actual array pattern deposited. When an error is detected deriving, based on the error, a corrected drive pattern different from the target drive pattern such that use of the corrected drive pattern results in a reduced discrepancy between the target and actual array patterns.

Claims

1. A method of fabricating an addressable array of biopolymer probes on a substrate according to a target array pattern using a deposition apparatus which, when operated according to a target drive pattern based on nominal operating parameters of the apparatus and determined by a processor in communication with the deposition apparatus, provides the probes on the substrate in the target array pattern, the method comprising:

(a) examining at least one operating parameter for an error from a nominal value which error will result in use of the target drive pattern producing a discrepancy between the target array pattern and an actual array pattern deposited;

(b) when an error is detected deriving, based on the error, a corrected drive pattern different from the target drive pattern such that use of the corrected drive pattern results in a reduced discrepancy between the target and actual array patterns; and

(c) operating the deposition apparatus according to the corrected drive pattern so as to fabricate the array;

wherein;

the deposition apparatus includes a dispensing head to dispense fluid droplets containing the probes or probe precursors, and a transport system to move at least one of the dispensing head and substrate relative to the other as the droplets are dispensed from the head, so as to form the array;

the drive pattern controls operation of the transport system; and

the operating parameter is the position of the dispensing head, which is examined by viewing the dispensing head.

2. A method according to claim 1 wherein the operating parameter is examined by viewing a fiducial mark on the dispensing head.

3. A method of fabricating an addressable array of biopolymer probes on a substrate according to a target array pattern using a deposition apparatus which, when operated according to a target drive pattern based on nominal operating parameters of the apparatus and determined by a processor in communication with the deposition apparatus, provides the probes on the substrate in the target array pattern, the method comprising:

(a) examining at least one operating parameter for an error from a nominal value which error will result in use of the target drive pattern producing a discrepancy between the target array pattern and an actual array pattern deposited;

(b) when an error is detected deriving, based on the error, a corrected drive pattern different from the target drive pattern such that use of the corrected drive pattern results in a reduced discrepancy between the target and actual array patterns; and

(c) operating the deposition apparatus according to the corrected drive pattern so as to fabricate the array;

wherein;

the deposition apparatus includes a dispensing head with multiple nozzles to dispense fluid droplets containing the probes or probe precursors, and a transport system to move at least one of the dispensing head and substrate relative to the other as the droplets are dispensed from the head, so as to form the array;

the drive pattern controls operation of the transport system;

the at least one operating parameter is the position of the substrate or dispensing head, or orientation of a nozzle, and is examined by viewing the dispensing head, or nozzle, or a droplet pattern previously dispensed from the head.

4. A method according to claim 3, additionally comprising operating the deposition apparatus according to the corrected drive pattern.

5. A method according to claim 3 wherein the probes are DNA or RNA probes.

6. A method according to claim 3 additionally comprising saving the target drive pattern in a memory of the deposition apparatus.

7. A method according to claim 6 additionally comprising saving the target drive pattern in a memory of a processor in communication with the deposition apparatus, and wherein the corrected drive pattern is saved in the memory, prior to operating the dispensing head and transport system to form the array.

8. A method according to claim 6 additionally comprising saving the target drive pattern in a memory of a processor in communication with the deposition apparatus, and wherein the corrected drive pattern is derived by modifying, based on the detected error, instructions to at least one deposition apparatus component based on the target drive pattern during operation of the dispensing head and transport system to form the array.

9. A method according to claim 3 additionally comprising saving the target drive pattern in a memory of the deposition apparatus, and wherein the corrected drive pattern is saved in the memory.

10. A method according to claim 3 wherein the at least one operating parameter is examined by viewing the droplet pattern previously dispensed from the head.

11. A method according to claim 3 wherein the at least one operating parameter is a position of the dispensing head.

12. A method according to claim 3 wherein the same error affects less than all of the array features.

13. A method of fabricating an addressable array of biopolymer probes on a substrate according to a target array pattern using a deposition apparatus which, when operated according to a target drive pattern based on nominal operating parameters of the apparatus and determined by a processor in communication with the deposition apparatus, provides the probes on the substrate in the target array pattern, the method comprising:

(a) examining at least one operating parameter for an error from a nominal value which error will result in use of the target drive pattern producing a discrepancy between the target array pattern and an actual array pattern deposited;

(b) when an error is detected deriving, based on the error, a corrected drive pattern different from the target drive pattern such that use of the corrected drive pattern results in a reduced discrepancy between the target and actual array patterns; and

(c) operating the deposition apparatus according to the corrected drive pattern so as to fabricate the array;

wherein;

the deposition apparatus includes a dispensing head with multiple nozzles to dispense fluid droplets containing the probes or probe precursors, and a transport system to move at least one of the dispensing head and substrate relative to the other as the droplets are dispensed from the head, so as to form the array;

the drive pattern controls operation of the transport system;

and wherein the at least one parameter is a position of a nozzle which is examined by viewing the nozzle, or a droplet pattern previously dispensed from the head.

14. A method of fabricating an addressable array of biopolymer probes on a substrate according to a target array pattern using a deposition apparatus which, when operated according to a target drive pattern based on nominal operating parameters of the apparatus and determined by a processor in communication with the deposition apparatus, provides the probes on the substrate in the target array pattern, the method comprising:

(a) examining at least one operating parameter for an error from a nominal value which error will result in use of the target drive pattern producing a discrepancy between the target array pattern and an actual array pattern deposited;

(b) when an error is detected deriving, based on the error, a corrected drive pattern different from the target drive pattern such that use of the corrected drive pattern results in a reduced discrepancy between the target and actual array patterns; and

(c) operating the deposition apparatus according to the corrected drive pattern so as to fabricate the array;

wherein the operating parameter is a fluid volume dispensed by the deposition apparatus.

15. A method according to claim 14 wherein the deposition apparatus comprises multiple jets for dispensing droplets, and wherein the corrected pattern is provided by a processor in communication with the deposition apparatus which provides an instruction to switch to a different jet when a deviation from nominal volume is encountered for one jet which is more than a predetermined tolerance.

16. A method of fabricating an addressable array of biopolymer probes on a substrate according to a target array pattern using a deposition apparatus which, when operated according to a target drive pattern based on nominal operating parameters of the apparatus and determined by a processor in communication with the deposition apparatus, provides the probes on the substrate in the target array pattern, the method comprising:

(a) examining at least one operating parameter for an error from a nominal value which error will result in use of the target drive pattern producing a discrepancy between the target array pattern and an actual array pattern deposited;

(b) when an error is detected deriving, based on the error, a corrected drive pattern different from the target drive pattern such that use of the corrected drive pattern results in a reduced discrepancy between the target and actual array patterns; and

(c) operating the deposition apparatus according to the corrected drive pattern so as to fabricate the array;

wherein the operating parameter is a position of a component which varies due to thermal expansion.

17. A method of fabricating an addressable array of biopolymer probes on a substrate according to a target array pattern using a deposition apparatus which, when operated according to a target drive pattern based on nominal operating parameters of the apparatus and determined by a processor in communication with the deposition apparatus, provides the probes on the substrate in the target array pattern, the method comprising:

(a) examining at least one operating parameter for an error from a nominal value which error will result in use of the target drive pattern producing a discrepancy between the target array pattern and an actual array pattern deposited,

(b) when an error is detected deriving, based on the error, a corrected drive pattern different from the target drive pattern such that use of the corrected drive pattern results in a reduced discrepancy between the target and actual array patterns; and

(c) operating the deposition apparatus according to the corrected drive pattern so as to fabricate the array;

wherein;

the deposition apparatus includes a dispensing head to dispense fluid droplets containing the probes or probe precursors, and a transport system to move at least one of the dispensing head and substrate relative to the other as the droplets are dispensed from the head, so as to form the array;

the apparatus further includes an encoder to provide data on the location of the substrate or head; and

the at least one operating parameter is an encoder error.

18. A method of fabricating an addressable array of biopolymer probes on a substrate according to a target array pattern using a deposition apparatus which, when operated according to a target drive pattern based on nominal operating parameters of the apparatus and determined by a processor in communication with the deposition apparatus, provides the probes on the substrate in the target array pattern, the method comprising:

(a) examining at least one operating parameter for an error from a nominal value which error will result in use of the target drive pattern producing a discrepancy between the target array pattern and an actual array pattern deposited;

(b) when an error is detected deriving, based on the error, a corrected drive pattern different from the target drive pattern such that use of the corrected drive pattern results in a reduced discrepancy between the target and actual array patterns; and

(c) operating the deposition apparatus according to the corrected drive pattern so as to fabricate the array;

wherein;

the deposition apparatus includes a dispensing head with multiple nozzles to dispense fluid droplets containing the probes or probe precursors, and a transport system to move at least one of the dispensing head and substrate relative to the other as the droplets are dispensed from the head, so as to form the array;

the drive pattern controls operation of the transport system;

the operating parameter is the position of the dispensing head, or orientation of a nozzle, and is examined by viewing the dispensing head, or nozzle.

19. A method of fabricating an addressable array of biopolymer probes on a substrate according to a target array pattern using a deposition apparatus which, when operated according to a target drive pattern based on nominal operating parameters of the apparatus and determined by a processor in communication with the deposition apparatus, provides the probes on the substrate in the target array pattern, the method comprising:

(a) examining at least one operating parameter for an error from a nominal value which error will result in use of the target drive pattern producing a discrepancy between the target array pattern and an actual array pattern deposited;

(b) when an error is detected deriving, based on the error, a corrected drive pattern different from the target drive pattern such that use of the corrected drive pattern results in a reduced discrepancy between the target and actual array patterns; and

(c) operating the deposition apparatus according to the corrected drive pattern so as to fabricate the array;

wherein the same error affects less than all of the array features.