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EP-4735944-A1 - DETILT FOCUS TRACKING

EP4735944A1EP 4735944 A1EP4735944 A1EP 4735944A1EP-4735944-A1

Abstract

An imaging system includes a focus tracking module including: a light source to project a first pair of spots on a sample; and a first image sensor to obtain one or more first images of the first pair of spots; a second image sensor to obtain one or more second images of the sample; one or more mirrors optically coupled to the second image sensor, the one or more mirrors positioned in an optical path from the sample to the second image sensor; and a controller to: determine, using at least a first separation distance measurement of the first pair of spots from the one or more first images, a first sample tilt of the sample about a first axis of the imaging system; and actuate, based at least on the first sample tilt, the one or more mirrors to offset the first sample tilt about the first axis.

Inventors

  • BLAIR, DUSTIN
  • HOLST, Gregory
  • SIU, Merek
  • SANGIORGIO, PAUL
  • WATSON, Dakota
  • CONDELLO, DANILO
  • EARNEY, John
  • NEWMAN, PETER

Assignees

  • Illumina, Inc.

Dates

Publication Date
20260506
Application Date
20240628

Claims (18)

  1. 1. An imaging system, comprising: a focus tracking module comprising: a light source to project a first pair of spots on a sample; and a first image sensor to obtain one or more first images of the first pair of spots at one or more sample locations of the sample; a second image sensor to obtain one or more second images of the sample; one or more mirrors optically coupled to the second image sensor, the one or more mirrors positioned in an optical path from the sample to the second image sensor; and a controller to: determine, using at least a first separation distance measurement of the first pair of spots from the one or more first images, a first sample tilt of the sample about a first axis of the imaging system; and actuate, based at least on the first sample tilt, the one or more mirrors to offset the first sample tilt about the first axis.
  2. 2. The imaging system of claim 1, wherein the one or more mirrors comprise a first mirror optically coupled to a second mirror, the first mirror adjustable about the first axis of the imaging system, and the second mirror adjustable about a second axis of the imaging system substantially orthogonal to the first axis.
  3. 3. The imaging system of claim 1, wherein the one or more mirrors comprise a mirror adjustable about the first axis and a second axis of the imaging system substantially orthogonal to the first axis.
  4. 4. The imaging system of claim 1, further comprising one or more actuators directly coupled to the one or more mirrors, wherein the controller is configured to control the one or more actuators to actuate, based at least on the first sample tilt, the one or more mirrors to offset the first sample tilt.
  5. 5. The imaging system of claim 1, wherein: the light source is to project a second pair of spots on the sample; the focus tracking module further comprises a third image sensor to obtain one or more third images of the second pair of spots at the one or more sample locations of the sample; the controller is to: determine, using at least the first separation distance measurement of the first pair of spots from the one or more first images and a second separation distance measurement of the second pair of spots from the one or more third images, the first sample tilt and a second sample tilt of the sample about a second axis substantially orthogonal to the first axis; and actuate, based at least on the first sample tilt and the second sample tilt, the one or more mirrors to offset the first sample tilt about the first axis and the second sample tilt about the second axis.
  6. 6. The imaging system of claim 5, wherein: the one or more mirrors comprise a first mirror and a second mirror; and the controller is to: actuate, based at least on the first sample tilt, the first mirror to offset the first sample tilt about the first axis; and actuate, based at least on the second sample tilt, the second mirror to offset the second sample tilt about the second axis.
  7. 7. The imaging system of claim 6, wherein: the first mirror is adjustable about the first axis of the imaging system; the second mirror is adjustable about a second axis of the imaging system; the one or more mirrors further comprise a third mirror optically coupled to the first mirror, and a fourth mirror optically coupled to the second mirror; and the controller is to: actuate, based at least on the first sample tilt, the first mirror and the third mirror to offset the first sample tilt about the first axis; and actuate, based at least on the second sample tilt, the second mirror and fourth mirror to offset the second sample tilt about the second axis.
  8. 8. The imaging system of claim 6, wherein each of the first mirror and the second mirror is adjustable about the first axis and the second axis of the imaging system.
  9. 9. The imaging system of claim 5, wherein: the first image sensor is a first linear sensor and the third image sensor is a second linear sensor parallel to the first linear sensor.
  10. 10. The imaging system of claim 5, wherein: the first pair of spots are projected using a first pair of light beams that are substantially parallel; the second pair of spots are projected using a second pair of light beams that are substantially parallel; the first pair of light beams are substantially parallel to the second pair of light beams; and the focus tracking module further comprises one or more light beam generation optics configured to generate the first pair of light beams and the second pair of light beams from an input light beam of the light source.
  11. 11. The imaging system of claim 10, wherein the one or more light beam generation optics comprise a first lateral displacement prism (LDP) optically coupled to a second LDP, the second LDP oriented orthogonal to the first LDP.
  12. 12. The imaging system of claim 10, wherein the one or more light beam generation optics comprise a two-dimensional grating optically coupled to a double roof prism.
  13. 13. The imaging system of claim 10, wherein the one or more light beam generation optics comprise a LDP optically coupled to a one-dimensional grating.
  14. 14. A focus tracking system, comprising: a light source to output an input light beam; one or more light beam generation optics configured to generate, from the input light beam, a first pair of light beams that are substantially parallel and a second pair of light beams that are substantially parallel, the first pair of light beams substantially parallel to the second pair of light beams; and one or more image sensors to obtain one or more first images of a first pair of spots at one or more sample locations of a sample, and one or more second images of a second pair of spots at the one or more sample locations of the sample, the first pair of spots obtained by projecting the first pair of light beams at the one or more sample locations, and the second pair of spots obtained by projecting the second pair of light beams at the one or more sample locations.
  15. 15. The focus tracking system of claim 14, wherein the one or more light beam generation optics comprise a first lateral displacement prism (LDP) optically coupled to a second LDP, the second LDP oriented orthogonal to the first LDP.
  16. 16. The focus tracking system of claim 14, wherein the one or more light beam generation optics comprise a two-dimensional grating optically coupled to a double roof prism.
  17. 17. The focus tracking system of claim 14, wherein the one or more light beam generation optics comprise a LDP optically coupled to a one-dimensional grating.
  18. 18. The focus tracking system of claim 14, wherein the one or more image sensors comprise: a first linear sensor to obtain the one or more first images; and a second linear sensor to obtain the one or more second images, the second linear sensor parallel to the first linear sensor.

Description

DETILT FOCUS TRACKING CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application claims the benefit of U.S. Provisional Patent Application No. 63/524,419, filed June 30, 2023, and titled “Detilt Focus Tracking”, which is incorporated herein by reference in its entirety. BACKGROUND [0002] Increasing the numerical aperture (NA) of optical imaging systems improves optical imaging resolution. In sequencing applications, this reduces sequencing cluster pitches and increases cluster density, enabling lower cost sequencing. However, increasing the NA also reduces the depth of field (DoF) - the distance over which the imaged object (e.g., cluster) remains in focus as an object is translated along an optical axis of the optical imaging system. [0003] As optical imaging systems with higher NAs continue to be used in imaging applications to reduce costs (e.g., to reduce sequencing costs), it becomes more difficult to ensure that an imaged sample will remain in focus as it is translated along an optical axis. For example, as illustrated by FIG. 1 A, some current sequencers are able to detilt or detip a sample by establishing a best fit plane for the entire sample such that the entire sample remains within the DoF of the optical imaging system. However, as illustrated by FIG. IB, with the reduction in the available DoF of the optical imaging system, and even with global adjustment of the sample tilt or tip, local tilt or tip within the sample itself may create DoF excursions large enough to cause at least part of the sequencing image to be out of focus, which causes poor data quality and data loss for the degraded parts of the image. SUMMARY [0004] Implementations of the disclosure relate to systems and methods for dynamically adjusting, based on a sample’s local topography, one or more components of an imaging system in one or more directions to keep the sample in focus during sample imaging. Additional implementations of the disclosure relate to an optical configuration of a focus tracking system that generates four substantially parallel optical beams that can be used for determining sample tilt about one or more directions. [0005] In one embodiment, an imaging system comprises: a focus tracking module comprising: a light source to project a first pair of spots on a sample; and a first image sensor to obtain one or more first images of the first pair of spots at one or more sample locations of the sample; a second image sensor to obtain one or more second images of the sample; one or more mirrors optically coupled to the second image sensor, the one or more mirrors positioned in an optical path from the sample to the second image sensor; and a controller to: determine, using at least a first separation distance measurement of the first pair of spots from the one or more first images, a first sample tilt of the sample about a first axis of the imaging system; and actuate, based at least on the first sample tilt, the one or more mirrors to offset the first sample tilt about the first axis. [0006] In some implementations, the one or more mirrors comprise a first mirror optically coupled to a second mirror, the first mirror adjustable about the first axis of the imaging system, and the second mirror adjustable about a second axis of the imaging system substantially orthogonal to the first axis. [0007] In some implementations, the one or more mirrors comprise a mirror adjustable about the first axis and a second axis of the imaging system substantially orthogonal to the first axis. [0008] In some implementations, the imaging system further comprises: one or more actuators directly coupled to the one or more mirrors, wherein the controller is configured to control the one or more actuators to actuate, based at least on the sample tilt, the one or more mirrors to offset the sample tilt. [0009] In some implementations, the light source is to project a second pair of spots on the sample; the focus tracking module further comprises a third image sensor to obtain one or more third images of the second pair of spots at the one or more sample locations of the sample; the controller is to: determine, using at least the first separation distance measurement of the first pair of spots from the one or more first images and a second separation distance measurement of the second pair of spots from the one or more third images, the first sample tilt and a second sample tilt of the sample about a second axis substantially orthogonal to the first axis; and actuate, based at least on the first sample tilt and the second sample tilt, the one or more mirrors to offset the first sample tilt about the first axis and the second sample tilt about the second axis. [0010] In some implementations, the one or more mirrors comprise a first mirror and a second mirror; and the controller is to: actuate, based at least on the first sample tilt, the first mirror to offset the first sample tilt about the first axis; actuate, based at least on the s