Methods and devices for reading microarrays

Patent metadata

Field	Value
Publication number	US-10586095-B2
Application number	US-201916374739-A
Country	US
Kind code	B2
Filing date	Apr 3, 2019
Priority date	May 22, 2009
Publication date	Mar 10, 2020
Grant date	Mar 10, 2020

Abstract

In one embodiment of the invention, a method to image a probe array is described that includes focusing on a plurality of fiducials on a surface of an array. The method utilizes obtaining the best z position of the fiducials and using a surface fitting algorithm to produce a surface fit profile. One or more surface non-flatness parameters can be adjusted to improve the flatness image of the array surface to be imaged.

First claim

What is claimed is:

1. A method for improving image flatness of a surface image of a probe array, the method comprising:
providing a probe array and one or more fiducials, said probe array comprising a plurality of sub-arrays;
imaging the one or more fiducials at one or more of positions;
determining a position measurement for each of the one or more fiducials;
generating a surface fit profile based on a plurality of the position measurements; and
imaging a sub-array and adjusting one or more surface non-flatness parameters based on the surface fit profile to improve the image flatness of the surface image of the sub-array.

2. The method of claim 1 , wherein the position measurement of each fiducial is determined based on image sharpness.

3. The method of claim 1 , wherein determining the position measurement comprises determining a best position measurement for each of the fiducials at which the imaging is sharpest.

4. The method of claim 1 , wherein determining the position measurement comprises using quadratic interpolation for at least one of the fiducials.

5. The method of claim 1 , wherein the surface fit profile is generated using a surface-fitting algorithm.

6. The method of claim 5 , wherein the surface-fitting algorithm comprises at least one of a least square algorithm, a sub-plane surface fit algorithm, and a B spline surface fit.

7. The method of claim 1 , wherein the one or more surface non-flatness parameters comprise a sub-array tilt angle.

8. The method of claim 1 , wherein adjusting the one or more surface non-flatness parameters comprises adjusting a position of a stage on which the probe array is mounted.

9. The method of claim 8 , wherein the stage is a two-axis tilt stage.

10. The method of claim 8 , wherein the stage is a three-axis translation stage.

11. The method of claim 1 , wherein the one or more surface non-flatness parameters comprise an optical parameter.

12. The method of claim 1 , wherein the one or more surface non-flatness parameters comprise a focal plane position.

13. The method of claim 1 , wherein the fiducials comprise at least 4, 5, 9, 12 or 15 fiducials.

14. The method of claim 1 , wherein the one or more fiducials are imaged at one or more positions along an axis of translation.

15. The method of claim 14 , wherein the axis of translation is substantially perpendicular to a plane of the probe array.

16. The method of claim 1 , wherein imaging the one or more fiducials comprises adjusting a position of a stage on which the probe array is mounted.

17. The method of claim 1 , wherein the probe array is a DNA array.

18. The method of claim 1 , wherein the probe array is a peptide array.

19. The method of claim 1 , wherein the one or more fiducials are on the probe array.

20. The method of claim 1 , wherein the one or more fiducials are of a corner sub-array of the probe array.

Assignees

• Affymetrix Inc

Inventors

• Stern David
• Gao Chuan
• Yamamoto Melvin
• Nguyen Devin

Classifications

• G01N21/6452 Primary

  Individual samples arranged in a regular 2D-array, e.g. multiwell plates · CPC title

• G02B21/16

  adapted for ultraviolet illumination {; Fluorescence microscopes (G02B21/0076 takes precedence)} · CPC title

• Y10T29/49826

  Assembling or joining · CPC title

• G02B21/0076

  arrangements using fluorescence or luminescence · CPC title

• G02B21/008

  Details of detection or image processing, including general computer control · CPC title