Predictive focus tracking apparatus and methods

Patent metadata

Field	Value
Publication number	US-11977213-B2
Application number	US-202117339587-A
Country	US
Kind code	B2
Filing date	Jun 4, 2021
Priority date	Jan 5, 2017
Publication date	May 7, 2024
Grant date	May 7, 2024

Abstract

An imaging system may include a sample stage comprising a surface to support a sample container, the sample container including a sample having a plurality of sample locations; an optical stage to image the sample at the plurality of sample locations; one or more actuators physically coupled to at least one of the sample stage and the optical stage to move the sample stage relative to the optical stage to focus the optical stage onto a current sample location of the plurality of sample locations; a first light source to illuminate the current sample location; a second light source to project a pair of spots on a next sample location of the plurality of sample locations; and a controller to determine, based on an image of the pair of spots projected on the next sample location, a focus setting for the next sample location.

First claim

We claim:

1. An imaging system, comprising:
a sample stage comprising a surface to support a sample container, the sample container including a sample having a plurality of sample locations;
an optical stage to image the sample at the plurality of sample locations;
one or more actuators physically coupled to at least one of the sample stage and the optical stage to move the sample stage relative to the optical stage to focus the optical stage onto a current sample location of the plurality of sample locations;
a first light source to illuminate the current sample location;
a second light source to project a pair of spots on a future sample location of the plurality of sample locations while the first light source is illuminating the current sample location or before at least one of the optical stage and the sample stage is positioned to image the sample at the future sample location; and
a controller to determine, based on an image of the pair of spots projected on the future sample location, a focus setting for the future sample location.

2. The imaging system of claim 1 , wherein the first light source is to illuminate fluorescent sequencing reactions within nucleic acid sequences at the current sample location.

3. The imaging system of claim 2 , wherein the sample container is a flowcell.

4. The imaging system of claim 2 , further comprising a camera to track sequencing of the sample container.

5. The imaging system of claim 1 , wherein the controller is further configured to provide, based on the focus setting for the future sample location, a drive signal to the one or more actuators before the optical stage is positioned to image the sample at the future sample location.

6. The imaging system of claim 5 , wherein the controller is further configured to determine at least one parameter of the drive signal using a difference between a focus setting for the current sample location and the focus setting determined for the future sample location.

7. The imaging system of claim 5 , wherein the one or more actuators are physically coupled to the sample stage to move, in response to the drive signal, the sample stage to adjust a distance between the sample stage and the optical stage.

8. The imaging system of claim 5 , wherein the one or more actuators are physically coupled to the optical stage to move, in response to the drive signal, the optical stage to adjust a distance between the sample stage and the optical stage.

9. The imaging system of claim 8 , wherein the optical stage comprises an objective lens that is moved in response to the drive signal.

10. The imaging system of claim 5 , wherein the one or more actuators are physically coupled to the sample stage to adjust, in response to the drive signal, a tilt of the sample stage.

11. The imaging system of claim 1 , wherein the one or more actuators comprise a piezoelectric device, a voice coil, or a drive motor.

12. The imaging system of claim 1 , wherein the second light source is to project the pair of spots on the future sample location of the plurality of sample locations while the first light source is illuminating the current sample location.

13. The imaging system of claim 1 , wherein the second light source is to project the pair of spots before at least one of the optical stage and the sample stage is positioned to image the sample at the future sample location.

14. The imaging system of claim 1 , wherein the second light source comprises:
a laser that emits a light beam; and
a beam splitter that splits the light beam into two light beams, wherein the pair of spots corresponds to the two light beams.

15. A method, comprising:
determining a first focus position of a sample stage for a current sample location of a sample in a sample container being sequenced;
moving, using one or more actuators, the sample stage relative to an optical stage to focus the optical stage onto the current sample location;
illuminating, using a first light source, the current sample location;
imaging, using the optical stage, the current sample location;
projecting, using a second light source, a pair of spots on a future sample location of the sample while the first light source is illuminating the current sample location or before at least one of the optical stage and the sample stage is positioned to image the sample at the future sample location; and
determining, based on an image of the pair of spots projected on the future sample location, a second focus position of the sample stage for the future sample location.

16. The method of claim 15 , wherein illuminating the current sample location, comprises: illuminating fluorescent sequencing reactions within nucleic acid sequences at the current sample location.

17. The method of claim 15 , further comprising: moving, based on at least the second focus position, using the one or more actuators, the sample stage relative to the optical stage to focus the optical stage onto the future sample location.

18. The method of claim 17 , wherein moving the sample stage relative to the optical stage to focus the optical stage onto the future sample location, comprises: providing a drive signal to the one or more actuators, the drive signal determined using at least the first focus position and the second focus position.

19. The method of claim 18 , wherein:
the one or more actuators are physically coupled to the optical stage; and
moving the sample stage relative to the optical stage to focus the optical stage onto the future sample location, comprises: moving, in response to the drive signal, the optical stage to adjust a distance between the sample stage and the optical stage.

20. The method of claim 18 , wherein:
the one or more actuators are physically coupled to the sample stage; and
moving the sample stage relative to the optical stage to focus the optical stage onto the future sample location, comprises: moving, in response to the drive signal, the sample stage to adjust a distance between the sample stage and the optical stage.

Assignees

• Illumina Inc

Inventors

• Arianpour Ashkan
• Bailey John
• Blair Dustin
• Chen Xiangling (Steve)
• Hong Stanley S
• Prince Simon
• Siu Merek C
• Zhou Chunhong (Allen)
• Condello Danilo

Classifications

• G02B21/002 Primary

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

• G02B7/09

  adapted for automatic focusing or varying magnification · CPC title

• G02B7/102

  controlled by a microcomputer (cameras with interchangeable lenses G03B17/14) · CPC title

• G02B21/006 Primary

  focusing arrangements; selection of the plane to be imaged · CPC title

• G02B21/245

  using auxiliary sources, detectors · CPC title