Methods and devices for reading microarrays

Patent metadata

Field	Value
Publication number	US-2018341802-A1
Application number	US-201815993512-A
Country	US
Kind code	A1
Filing date	May 30, 2018
Priority date	May 22, 2009
Publication date	Nov 29, 2018
Grant date	—

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

1 - 21 . (canceled)

22 . A method for improving image flatness of a surface image of a probe array having an array surface roughness, the method comprising:
imaging one or more fiducials of the probe array and determining a position measurement for each of the one or more fiducials based on at least image sharpness; generating a surface fit profile based on one or more of the position measurements; and imaging the probe 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 probe array.

23 . The method of claim 22 , wherein the one or more fiducials are imaged at one or more positions along an axis of translation.

24 . The method of claim 22 , wherein the surface fit profile is generated using a surface-fitting algorithm.

25 . The method of claim 24 , 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.

26 . The method of 22 , wherein determining the position measurement comprises using quadratic interpolation for at least one of the one or more fiducials.

27 . The method of claim 22 , wherein the one or more surface non-flatness parameters comprises a probe array tilt angle.

28 . The method of claim 27 , wherein adjusting the one or more surface non-flatness parameters comprises adjusting a position of a stage on which the probe array is mounted.

29 . The method of claim 28 , wherein the stage comprises a two-axis tilt stage.

30 . The method of claim 28 , wherein the stage comprises a three-axis translation stage.

31 . The method of claim 22 , wherein the one or more surface non-flatness parameters comprise an optical parameter.

32 . The method of claim 22 , wherein the one or more surface non-flatness parameters comprise a focal plane position.

33 . The method of claim 22 , wherein the one or more fiducials comprise at least 4 fiducials.

34 . The method of claim 33 , wherein the one or more fiducials comprise at least 5 fiducials.

35 . The method of claim 34 , wherein the one or more fiducials comprise at least 9 fiducials.

36 . The method of claim 35 , wherein the one or more fiducials comprise 12 fiducials.

37 . The method of claim 36 , wherein the one or more fiducials comprise 15 fiducials.

38 . The method of claim 22 , wherein the axis of translation is substantially perpendicular to a plane of the probe array.

39 . The method of claim 22 , wherein imaging the one or more fiducials comprises adjusting a position of a stage on which the probe array is mounted.

40 . The method of claim 22 , wherein the probe array comprises a DNA array.

41 . The method of claim 22 , wherein the probe array comprises a peptide array.

42 . The method of claim 22 , wherein the probe array comprises a plurality of sub-arrays.

43 . The method of claim 42 , wherein the one or more fiducials are of a corner sub-array of the probe array.

44 . The method of claim 42 , wherein the probe array is positioned such that a selected sub-array is centered in a field of view of an image detector device.

45 . The method of claim 22 , wherein the one or more fiducials comprise a plurality of fiducials located in non-collinear locations on the probe array.

46 . The method of claim 22 , wherein the one or more fiducials comprise one of an L-shaped or square shaped feature.

47 . The method of claim 22 , wherein at least one of the one or more fiducials is located near a middle of the probe array.

48 . A system for improving image flatness of a surface image of a probe array having an array surface roughness, the system comprising:
an image detector device configured to:
image one or more fiducials of the probe array and determine a position measurement for each of the one or more fiducials based on at least image sharpness; and
at least one server coupled with the image detector device and that is, upon execution of software instructions stored in a non-transitory computer readable memory by at least one processor, configurable to:
generate a surface fit profile based on one or more of the position measurements; and
facilitate imaging the probe array by 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 probe array.

49 . A computer program product embedded in a non-transitory computer readable medium comprising instructions executable by a computer processor for improving image flatness of a surface image of a probe array having an array surface roughness, the instructions being executable by a computer processor to execute processing comprising:
imaging one or more fiducials of the probe array and determining a position measurement for each of the one or more fiducials based on at least image sharpness; generating a surface fit profile based on one or more of the position measurements; and imaging the probe 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 probe array.

Assignees

• Affymetrix Inc

Inventors

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

Classifications

• G02B21/0076

  arrangements using fluorescence or luminescence · CPC title

• G02B21/361

  Optical details, e.g. image relay to the camera or image sensor (G02B21/364 takes precedence; illumination details G02B21/06 and subgroups) · CPC title

• Y10T29/49826

  Assembling or joining · CPC title

• G02B21/16

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

• G01N21/6452 Primary

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