Modular optical analytic systems and methods

Patent metadata

Field	Value
Publication number	US-12044626-B2
Application number	US-202217857817-A
Country	US
Kind code	B2
Filing date	Jul 5, 2022
Priority date	Jan 5, 2017
Publication date	Jul 23, 2024
Grant date	Jul 23, 2024

Abstract

A system includes a plurality of modular subassemblies and a plate; wherein each modular subassembly comprises an enclosure and a plurality of optical components aligned to the enclosure, and each enclosure comprises a plurality of mounting structures; and wherein each modular subassembly is mechanically coupled to the plate by attachment of a mounting structure of the modular subassembly directly to a corresponding mounting structure located on the plate, such that by mechanically coupling each modular subassembly to the plate using the mounting structure of the modular subassembly and the corresponding mounting structure on the plate, adjacent modular subassemblies are aligned to each other upon such attachment, and wherein two of the modular subassemblies mechanically coupled to the plate are also attached to each other by mechanically coupling an alignment structure on one of the two modular subassemblies to a respective alignment structure on the other of the two modular subassemblies.

First claim

We claim:

1. A system comprising:
a plate; and
a plurality of modular subassemblies configured to mechanically couple to a respective plurality of alignment structures on the plate such that adjacent modular subassemblies are aligned to each other upon coupling, the plurality of modular subassemblies including:
a first subassembly comprising a light source configured to generate a light beam;
a second subassembly comprising an objective and a tube lens, the objective to focus the light beam onto a surface of a flow cell and the tube lens including a lens element configured to articulate along a longitudinal axis within the tube lens to correct for spherical aberration introduced by moving objective along a z-axis; and
a third subassembly comprising a focus tracking light source, a focus tracking sensor, and a semi-reflective mirror,
the focus tracking light source to generate a focus tracking light beam and transmit the focus tracking light beam through the objective such that the focus tracking light beam terminates at the focus tracking sensor, and
the semi-reflective mirror configured to reflect the focus tracking light beam generated by the focus tracking light source onto the flow cell, and configured to reflect light returned from the flow cell onto the focus tracking sensor.

2. The system of claim 1 , wherein the first subassembly comprises a beam shaping lens positioned within an optical path of the light source such that the light beam is directed through the beam shaping lens.

3. The system of claim 2 , wherein the light source is a first light source operating at a first wavelength and the first subassembly further comprises:
a second light source operating at a second wavelength, wherein the beam shaping lens is positioned within the optical path of the second light source such that a light beam output from the second light source is directed through the beam shaping lens.

4. The system of claim 3 , wherein the first wavelength is a green wavelength or a blue wavelength, the second wavelength is a green wavelength or a red wavelength, and the beam shaping lens is a Powell lens.

5. The system of claim 1 , further comprising:
a processor; and
a non-transitory computer readable medium with machine-readable instructions stored thereon that when executed by the processor cause the processor to:
receive an output signal from the focus tracking sensor; and
analyze the output signal to determine a set of characteristics of the focus tracking light beam.

6. The system of claim 1 , wherein the objective is to focus the light beam on the flow cell and the plurality of modular subassemblies further comprises:
a fourth subassembly including a detector to detect light emanating from the flow cell.

7. The system of claim 1 , wherein the flow cell comprises:
a translucent cover plate;
a substrate; and
a channel between the translucent cover and the substrate configured to have liquid flow therethrough.

8. The system of claim 1 , wherein at least one of the modular subassemblies is a field replaceable unit.

9. The system of claim 1 , wherein the alignment structures comprise at least one of a slot, a datum, a tab, a pin, or a recessed cavity.

10. The system of claim 1 , wherein a z-stage is configured to actuate the objective along a longitudinal axis of the objective to move a focal point of the objective with respect to one or more surfaces of the flow cell.

11. A method comprising:
obtaining a first enclosure comprising a light source configured to generate a light beam;
obtaining a second enclosure comprising an objective and a tube lens including a lens element that is articulatable within the tube lens;
obtaining a third enclosure comprising a focus tracking light source, a focus tracking sensor, and a semi-reflective mirror, the focus tracking light source to generate a focus tracking light beam and transmit the focus tracking light beam through the objective such that the focus tracking light beam terminates at the focus tracking sensor, and the semi-reflective mirror configured to reflect the focus tracking light beam generated by the focus tracking light source onto a flow cell, and configured to reflect light returned from the flow cell onto the focus tracking sensor;
mounting the first enclosure and the second enclosure to a plate such that the objective is optically aligned with the light source;
mounting the third enclosure to the plate such that the objective is optically aligned with the focus tracking light source; and
correcting for spherical aberration introduced by movement of the objective by articulating the lens element within the tube lens.

12. The method of claim 11 , further comprising:
obtaining a fourth enclosure comprising a detector to detect light emanating from fluorophores located on the flow cell; and
mounting the fourth enclosure to the plate.

13. A method comprising:
providing a plate;
providing a first enclosure mounted on the plate and enclosing first optical elements, wherein the first optical elements are optically aligned within the first enclosure;
providing a second enclosure mounted on the plate and enclosing second optical elements, wherein the second optical elements are optically aligned within the second enclosure;
providing a third enclosure and enclosing third optical elements, wherein the third optical elements are optically aligned within the third enclosure, the third enclosure being a field replaceable unit for the first enclosure;
providing a fourth enclosure and enclosing fourth optical elements, wherein the fourth optical elements are optically aligned within the fourth enclosure;
mounting the fourth enclosure to the plate; and
replacing the first enclosure with the third enclosure, wherein:
the third optical elements comprise a light source and the second optical elements comprise a tube lens and an objective, the tube lens comprising a lens element within the tube lens to articulate therein to correct for spherical aberration cause by movement of the objective along a z-axis,
the fourth optical elements comprise a focus tracking light source, a focus tracking sensor, and a semi-reflective mirror, the focus tracking light source to generate a focus tracking light beam and transmit the focus tracking light beam through the objective such that the focus tracking light beam terminates at the focus tracking sensor, and the semi-reflective mirror configured to reflect the focus tracking light beam generated by the focus tracking light source onto a flow cell, and configured to reflect light returned from the flow cell onto the focus tracking sensor,
the replacing causes precision alignment structures on the second enclosure, the third enclosure, or the plate to align the third enclosure with the second enclosure, and
mounting the fourth enclosure to the plate comprises mounting the fourth enclosure such that the objective is optically aligned with the focus tracking light source.

14. The method of claim 13 , further comprising:
articulating the objective along the z-axis to move a focal point of the objective with respect to one or more surfaces of the flow cell.

15. The method of claim 14 , further comprising:
articulating the lens element along a longitudinal axis of the tube lens.

16. The method of claim 13 , further comprising:
providing a fifth enclosure comprising a detector to detect light emanating from the flow cell; and
mounting the fifth enclosure to the plate.

Assignees

• Illumina Inc

Inventors

• Feng Wenyi
• Prince Simon
• Newman Peter Clarke
• Watson Dakota
• Hong Stanley S
• Krumbuegel Marco A
• Sun Yinghua
• Carson Andrew James
• Siu Merek C

Classifications

• G01N15/01

  specially adapted for biological cells, e.g. blood cells (investigating sedimentation of particle suspensions in blood G01N15/05) · CPC title

• G01N21/6458

  Fluorescence microscopy (fluorescence microscopes per se G02B21/0076 and G02B21/16) · CPC title

• G01N2201/024

  Modular construction · CPC title

• C12Q1/6869 Primary

  Methods for sequencing · CPC title

• G02B7/003

  Alignment of optical elements (G02B7/001, G02B7/002 take precedence; for mirrors G02B7/1822) · CPC title