Apparatus for deposition and inspection of chemical and biological fluids

• US 6,689,319 B1
• Filed: 10/29/1999
• Issued: 02/10/2004
• Est. Priority Date: 10/29/1999
• Status: Expired due to Fees

• Current Assignee: Agilent Technologies, Inc.
• Original Assignee: Agilent Technologies Europe BV (Agilent Technologies, Inc.)
• Inventors: Webb, Peter G., Martins, Henrique A. S., Fisher, William D.
• Primary Examiner(s): SNAY, JEFFREY R
• Application Number:
  US09/429,895
• Time in Patent Office: 1,565 Days
• Field of Search: 422/62-63, 422/67, 422/100, 422/82.05, 436/43, 436/49, 436/55, 436/180, 436/518, 435/287--28, 347/20, 347/106, 347/37, 356/394, 356/398, 250/559.07, 250/559.08, 250/559.29
• 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 2219/00351 Means for dispensing and evacuation of reagents
• 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 2219/00596 Solid-phase processes
• CPC Class Codes: B01J 2219/00605 the compounds being directly bound or immobilised to solid supports
• CPC Class Codes: B01J 2219/00612 the surface being inorganic
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• 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: B41J 29/393 Devices for controlling or analysing the entire machine ; Controlling or analysing mechanical parameters involving printing of test patterns
• 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 21/95607 using a comparative method

Abstract

An apparatus and method are provided for producing and inspecting a plurality of deposited features in a pattern on a portion of a substrate surface, as in an oligonucleotide array. The apparatus comprises a printhead for depositing a fluid to form the array of features on the substrate surface and a camera for imaging the deposited features. The apparatus also comprises a printhead controller for positioning and activating the inkjet printhead to deposit the array features. The camera, e.g., a digital line scan camera, is controlled by a camera controller such that the camera acquires images corresponding to substantially only the portion of the surface on which features should have been deposited. The camera and printhead are preferably situated such that an induced movement of the printhead relative to the substrate results in a substantially identical corresponding movement of the camera. Optionally, the apparatus further comprises means for comparing an image acquired by the camera with a predetermined standard to produce a signal.

Claims

1. An apparatus for producing and inspecting a plurality of features in a pattern on a surface of a substrate, comprising:

a printhead that deposits a fluid to form a plurality of features in a pattern on a first portion of a substrate surface, leaving a second intervening portion of the substrate surface nominally featureless;

an image acquisition system that images the substrate surface, said image acquisition system comprising;

a camera and a camera controller that positions and activates said camera to image in a two-dimensional manner by moving the camera across said first portion in a perpendicular direction with respect to a line of said features to acquire images corresponding to said first portion and less than all of said second portion; and

a printhead controller that positions the printhead relative to the substrate surface and activates the printhead to sequentially deposit the plurality of features in the pattern.

2. The apparatus of claim 1 wherein activation of the printhead by the printhead controller is accompanied by corresponding imaging by the image acquisition system.

3. The apparatus of claim 1 wherein an induced movement of the printhead relative to the substrate results in a corresponding movement of the image acquisition system relative to the substrate.

4. The apparatus of claim 3 wherein the corresponding movement is substantially identical in direction and distance to the induced movement of the printhead.

5. The apparatus of claim 2 wherein the printhead controller is computerized.

6. The apparatus of claim 1 wherein the image acquisition system comprises a digital camera.

7. The apparatus of claim 6 wherein the camera is a line scan camera.

8. The apparatus of claim 6 wherein the camera acquires data at a peak rate of at least about 20 megabytes of data per second.

9. The apparatus of claim 5 wherein the printhead controller functions as said camera controller.

10. The apparatus of claim 7 wherein the line scan camera comprises a line of pixels activated according to a data file.

11. The apparatus of claim 1 further comprising means for illuminating the substrate surface.

12. The apparatus of claim 6 further comprising means for comparing an image acquired by the camera with a predetermined standard to produce a signal.

13. The apparatus of claim 12 further comprising means for conveying the signal to the printhead controller to alter the positioning and activating of the printhead.

14. The apparatus of claim 1 wherein the substrate is transparent.

15. The apparatus of claim 1 wherein the fluid comprises a biomolecule.

16. The apparatus of claim 1 wherein the fluid comprises an oligonucleotide, polynucleotide, oligopeptide, or polypeptide.

17. The apparatus of claim 1 wherein the printhead is an inkjet printhead.

18. The apparatus of claim 1 wherein the pattern is an array.

19. The apparatus of claim 1 wherein the plurality comprises at least 1,000 features.

20. The apparatus of claim 19 wherein the plurality comprises at least 100,000 features.

21. The apparatus of claim 1 wherein said camera controller activates said camera to acquire images corresponding to said first portion and no more than about fifty percent of the second portion of the surface.

22. The apparatus of claim 21 wherein said camera controller activates said camera to acquire images corresponding to said first portion and no more than about twenty-five percent of the second portion of the surface.

23. The apparatus of claim 22 wherein said camera controller activates said camera to acquire images corresponding to said first portion and no more than about ten percent of the second portion of the surface.

24. An apparatus for producing and inspecting a plurality of features in a pattern on a surface of a substrate, said apparatus comprising:

a printhead that deposits a fluid to form a plurality of features in a pattern on a first portion of a substrate surface, leaving a second intervening portion of the substrate surface nominally featureless;

an image acquisition system that images the substrate surface, said image acquisition system comprising;

a camera and

a camera controller comprising hardware and/or software that activates said camera, when said camera is positioned to detect a portion of the substrate surface on which a feature should have been deposited, to image in a two-dimensional manner by moving the camera across said first portion in a perpendicular direction with respect to a line of said features to acquire images corresponding to said first portion and less than all of said second portion; and

a printhead controller that positions the printhead relative to the substrate surface and activates the printhead to sequentially deposit the plurality of features in the pattern.

25. An apparatus for producing and inspecting an array of nucleic acid features on a surface of a substrate, said apparatus comprising:

a printhead that deposits a fluid to form an array of nucleic acid features on a first portion of a substrate surface, leaving a second intervening portion of the substrate surface nominally featureless;

an image acquisition system that images the substrate surface, said image acquisition system comprising;

a line scan camera comprising a line of pixels and

a camera controller that positions and activates said camera to image in a two-dimensional manner by moving the camera across said first portion in a perpendicular direction with respect to the line of pixels to acquire images corresponding to said first portion and less than all of said second portion; and

a printhead controller that positions the printhead relative to the substrate surface and activates the printhead to sequentially deposit the fluid to form said array of nucleic acid features on the substrate surface.