Chemical array fabrication errors

• US 7,101,508 B2
• Filed: 07/31/2002
• Issued: 09/05/2006
• Est. Priority Date: 07/31/2002
• Status: Expired due to Fees

• Current Assignee: Agilent Technologies, Inc.
• Original Assignee: Agilent Technologies, Inc.
• Inventors: Thompson, Allen C., Caren, Michael P., Fisher, William D.
• Primary Examiner(s): Gordon, Brian R.
• Application Number:
  US10/210,126
• Publication Number:
  US 20040023223A1
• Time in Patent Office: 1,497 Days
• Field of Search: 422/100, 422/63, 422/67, 422/68.1, 422/82.05, 382/149, 382/151, 382/287, 382/291, 436/180
• US Class Current: 422/67
• 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 2219/00529 DNA chips
• 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 2219/0061 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 2219/00691 using robots
• CPC Class Codes: B01J 2219/00693 Means for quality control
• 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: G01N 2035/00158 Elements containing microarrays, i.e. "biochip"
• CPC Class Codes: G01N 35/1011 Control of the position or alignment of the transfer device
• CPC Class Codes: Y10T 436/2575 Volumetric liquid transfer

Abstract

A method of fabricating an addressable array of chemical probes at respective feature locations on a substrate surface. The method may use a deposition apparatus with a substrate unit which includes the substrate and with a drop deposition unit which includes a drop deposition head. Such an apparatus when operated according to a target drive pattern based on nominal operating parameters of the apparatus provides the probes on the substrate surface in the target array pattern. The method may include depositing at least one drop from the head unit onto the substrate surface. A fiducial on the substrate unit is optionally viewed from a sensor. A deposited drop on the substrate surface is viewed from a sensor. An actual position of the viewed deposited drop may be determined relative to a fiducial on the substrate unit, based on the views of the fiducial and deposited drop. An error is determined based on any difference between the actual and target positions. Alternatively, an error for one or more deposition units may be determined based on a statistical difference between the actual and target positions of a set of multiple drops deposited from each deposition unit. The deposition apparatus is operated to deposit further drops from the head unit onto the substrate surface at feature locations while moving at least one of the substrate unit or head unit with respect to the other, so as to fabricate the array. Apparatus and computer program products are also provided.

Claims

1. An apparatus for fabricating an addressable array having multiple features carrying chemical probes at different locations on a substrate surface, which when operated according to a target drive pattern based on nominal operating parameters of the apparatus provides the probes on the substrate surface in a target array pattern, the apparatus comprising:

a) a substrate unit which comprises a substrate holder and optionally a substrate received on the holder;

b) a drop deposition unit which includes a drop deposition head;

c) a transport system to move the deposition unit with respect to a received substrate;

d) at least one sensor;

e) a control unit which includes a processor programmed to operate the apparatus to;

i) deposit at least one drop from the head unit onto a received substrate surface;

ii) view a fiducial on the substrate unit from a sensor;

iii) view a deposited drop on the substrate surface, from a sensor;

iv) determine an actual position of the viewed deposited drop relative to a fiducial on the substrate unit, based on the views of the fiducial and deposited drop;

v) determine an error based on any difference between the actual and target positions;

vi) deposits further drops from the head unit onto the substrate surface at feature locations while moving at least one of the substrate unit or head unit with respect to the other, so as to fabricate the array.

2. An apparatus according to claim 1 wherein the sensors in (ii) and (iii) are on the drop deposition unit.

3. An apparatus according to claim 1 wherein the control unit operates the apparatus such that multiple fiducials are viewed in (ii), and an actual position of the viewed deposited drop is determined in (iv) relative to a fiducial based on the views of the multiple fiducials and the view of the deposited drop.

4. An apparatus according to claim 1 wherein the control unit operates the apparatus such that:

multiple drops are deposited in (i) at different locations on the substrate surface which multiple drops are viewed in (iii);

an actual position of the viewed deposited drops relative to a fiducial on the substrate unit is determined in (iv), based on the views of the fiducial and deposited drops; and

the error is determined in (v) based on a statistical difference between the actual and target positions.

5. An apparatus according to claim 4 wherein the statistical difference is an average difference between the actual and target positions.

6. An apparatus according to claim 1 wherein the deposited drop and fiducial in (i) and (ii) are viewed in a same image captured by the same sensor.

7. An apparatus according to claim 1 wherein the control unit additionally:

derives a corrected drive pattern when an error is detected, said corrected drive pattern being 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

wherein the deposition apparatus is operated in according to the corrected drive pattern so as to fabricate the array.

8. An apparatus according to claim 1 wherein the processor additionally:

determines the actual positions of the further drops deposited and viewed in (vi) based on the views and the determined error; and

saves the determined actual positions to a memory.

9. An apparatus according to claim 1 wherein said controller further generates an updated drive pattern based on said determination of error.

10. An apparatus according to claim 9 wherein said updating results in a corrected drive pattern.

11. An apparatus according to claim 10 wherein said correction of the drive pattern occurs while the drop deposition unit is depositing drops on the substrate surface.