Method for imaging high density biochemical arrays with sub-pixel alignment

Patent metadata

Field	Value
Publication number	US-9285578-B2
Application number	US-201514594979-A
Country	US
Kind code	B2
Filing date	Jan 12, 2015
Priority date	Oct 26, 2010
Publication date	Mar 15, 2016
Grant date	Mar 15, 2016

Abstract

A method and associated system for imaging high density biochemical arrays comprises one or more imaging channels that share a common objective lens and a corresponding one or more time delay integration-type imaging cameras with optical alignment mechanisms that permit independent inter-channel and intra-channel adjustment of each of four degrees: X, Y, rotation and scale. The imaging channels are configured to independently examine different spectra of the image of the biochemical arrays.

First claim

What is claimed is:

1. A method for aligning an imaging system having a microscope objective and a multichannel imager, the method comprising:
(a) collecting light emitted from a sample on an x-y positioning stage;
(b) obtaining an image of the sample along a rotational axis of symmetry of the microscope objective;
(c) calculating a first angle between the multichannel imager and the sample around the rotational axis of symmetry;
(d) calculating a second angle between the sample and the x-y positioning stage around the axis of rotational symmetry;
(e) rotating the sample by the second angle to align the sample with the x-y positioning stage; and
(f) rotating the multichannel imager by the sum of the first angle and the second angle to align the camera with the x-y positioning stage.

2. The method of claim 1 , further comprising:
(g) repeating steps (c) and (d) to determine whether either the first angle between the camera and the sample or the second angle between the sample and the x-y positioning stage is zero; and
(h) repeating steps (a) through (g) if the first angle or the second angle is not zero.

3. The method of claim 1 , further comprising:
(g) performing a scanning operation to acquire image data of the sample in a plane normal to the axis of rotational symmetry.

4. The method of claim 3 , wherein performing the scanning operation comprises:
(h) correcting a positioning error during the scanning operation by using an image-based control loop.

5. The method of claim 3 , wherein performing the scanning operation comprises:
(h) making dynamic adjustments that include an X offset and a Y offset.

6. The method of claim 5 , wherein making the dynamic adjustments comprises:
(i) reading the image data from the camera;
(j) calculating error corrections based on the image data;
(k) based on the error corrections, calculating the X offset and the Y offset respectively for an X direction and a Y direction in the plane normal to the axis of rotational symmetry; and
(l) applying the X offset and the Y offset prior to acquiring subsequent image data of the sample.

7. The method of claim 6 , wherein applying the X offset comprises a member of the group consisting of:
rotating an offset plate based on the X offset;
rotating a mirror based on the X offset;
translating the x-y positioning stage based on the X offset; and
translating the x-y positioning stage based on the Y offset.

8. The method of claim 6 , wherein the multichannel imager is a TDI camera, and wherein applying the Y offset comprises:
(m) changing the pulse timing of the TDI camera based on the Y offset.

Assignees

• Complete Genomics Inc

Inventors

• Staker Bryan P
• Uhrich Craig E

Classifications

• H04N25/711

  Time delay and integration [TDI] registers; TDI shift registers · CPC title

• G02B21/002

  Scanning microscopes (scanning near field optical microscopes G01Q60/18) · 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

• H04N5/37206

  Electricity · mapped topic

• G02B21/365 Primary

  Control or image processing arrangements for digital or video microscopes (G02B21/361, G02B21/362 take precedence) · CPC title