Methods, carrier assemblies, and systems for imaging samples for biological or chemical analysis

• US 9,976,174 B2
• Filed: 03/22/2016
• Issued: 05/22/2018
• Est. Priority Date: 03/24/2015
• Status: Active Grant

• Current Assignee: Illumina Cambridge Ltd. (California) (Illumina Incorporated)
• Original Assignee: Illumina Cambridge Ltd. (California) (Illumina Incorporated)
• Inventors: Rawlings, Stephen, Rao, Venkatesh Mysore Nagaraja, Ang, Beng Keong, Udpa, Nitin
• Primary Examiner(s): Bhat, Narayan
• Application Number:
  US15/077,182
• Publication Number:
  US 20160281150A1
• Time in Patent Office: 791 Days
• Field of Search: 4352831
• CPC Class Codes: B01L 2300/0654 Lenses; Optical fibres
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0822 Slides
• CPC Class Codes: B01L 2300/0877 Flow chambers
• CPC Class Codes: B01L 3/5027 by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip B01L3/5023 takes precedence; micromixers B01F33/30; microreactors for synthesis B01J19/0093; microcapillary devices in general B81B1/00
• CPC Class Codes: B01L 7/52 with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples amplification or hybridisation processes per se C12Q1/68; controlling sequential reactions for synthesis B01J19/0046
• CPC Class Codes: B01L 9/52 Supports specially adapted for flat sample carriers, e.g. for plates, slides, chips
• CPC Class Codes: B01L 9/527 for microfluidic devices, e.g. used for lab-on-a-chip
• CPC Class Codes: C12Q 1/6837 using probe arrays or probe chips C12Q1/6874 takes precedence
• CPC Class Codes: C12Q 1/6869 Methods for sequencing
• CPC Class Codes: G01N 2035/00356 Holding samples at elevated temperature (incubation)
• CPC Class Codes: G01N 2035/00752 bar codes
• CPC Class Codes: G01N 2035/0091 GUI [graphical user interfaces]
• CPC Class Codes: G01N 21/13 Moving of cuvettes or solid samples to or from the investigating station handling materials for automatic analysis G01N35/00
• CPC Class Codes: G01N 21/253 for batch operation, i.e. multisample apparatus analytical automats G01N35/00
• CPC Class Codes: G01N 21/6452 Individual samples arranged in a regular 2D-array, e.g. multiwell plates
• CPC Class Codes: G01N 2201/025 Mechanical control of operations
• CPC Class Codes: G01N 35/04 Details of the conveyor system G01N35/021 - G01N35/028 take precedence
• CPC Class Codes: G01N 35/1095 for supplying the samples to flow-through analysers for a specific analyser see relevant groups, e.g. under G01N15/00, G01N21/00, G01N27/00, G01N30/00, H01J49/00
• CPC Class Codes: G02B 21/34 Microscope slides, e.g. mounting specimens on microscope slides

Abstract

Method includes positioning a first carrier assembly on a system stage. The carrier assembly includes a support frame having an inner frame edge that defines a window of the support frame. The first carrier assembly includes a first substrate that is positioned within the window and surrounded by the inner frame edge. The first substrate has a sample thereon. The method includes detecting optical signals from the sample of the first substrate. The method also includes replacing the first carrier assembly on the system stage with a second carrier assembly on the system stage. The second carrier assembly includes the support frame and an adapter plate held by the support frame. The second carrier assembly has a second substrate held by the adapter plate that has a sample thereon. The method also includes detecting optical signals from the sample of the second substrate.

Claims

1. A method comprising:

positioning a first carrier assembly on a system stage, the first carrier assembly including a support frame having an inner frame edge that defines a window of the support frame, the first carrier assembly including a removable first substrate that is positioned within the window and surrounded by the inner frame edge, the first substrate having a sample thereon that is positioned within an imaging zone of an optical system;

detecting optical signals from the sample of the first substrate using the optical system in accordance with a first imaging protocol;

replacing the first carrier assembly with a second carrier assembly on the system stage, the second carrier assembly having a removable second substrate, the second substrate having a sample thereon that is positioned within the imaging zone of the optical system, wherein the first and second substrates are different types of substrates; and

detecting optical signals from the sample of the second substrate using the optical system in accordance with a second imaging protocol that is different from the first imaging protocol,

wherein each of the first and second carrier assemblies includes apertures that extend into the respective carrier assembly, the apertures receiving corresponding datums when the respective carrier assembly is positioned on the system stage, wherein the first substrate engages the datums and the second substrate does not engage the datums.

2. The method of claim 1, wherein the first substrate includes a flow cell, the flow cell including a flow channel that extends between inlet and outlet ports of the flow cell, the inlet and outlet ports being fluidically coupled to a manifold for flowing a liquid through the flow channel.

3. The method of claim 2, further comprising iteratively flowing reagents through the flow cell to conduct a sequencing-by-synthesis (SBS) protocol.

4. The method of claim 1, wherein the first and second imaging protocols include moving an objective lens and/or the system stage relative to each other along different respective paths.

5. The method of claim 1, wherein the second substrate is an open-face substrate having biological or chemical substances immobilized to an exterior surface of the open-face substrate, wherein the open-face substrate includes a microarray along the exterior surface, wherein the microarray includes a plurality of feature stripes that extend parallel to each other, each of the feature stripes having an array of reaction sites.

6. The method of claim 1, wherein the optical system includes an objective lens, wherein detecting the optical signals from the first substrate includes moving the objective lens and the first substrate relative to each other, wherein detecting the optical signals from the second substrate includes moving the objective lens and the second substrate relative to each other, wherein the optical system detects the optical signals from the first substrate along a first imaging zone, the optical system detecting the optical signals from the second substrate along a second imaging zone, the first and second imaging zones being sized differently.

7. The method of claim 6, wherein the first and second imaging protocols include automatically moving the objective lens relative to the first and second substrates, respectively, along different paths.

8. A method comprising:

positioning a first carrier assembly on a system stage, the first carrier assembly including a support frame having an inner frame edge that defines a window of the support frame, the first carrier assembly including a first substrate that is positioned within the window and surrounded by the inner frame edge, the first substrate having a sample thereon that is positioned within an imaging zone of an optical system;

detecting optical signals from the sample of the first substrate using the optical system;

replacing the first carrier assembly with a second carrier assembly on the system stage, the second carrier assembly including a support frame and an adapter plate coupled to the support frame, the second carrier assembly having a second substrate held by the adapter plate that has a sample thereon, the sample of the second substrate being positioned within the imaging zone of an optical system; and

detecting optical signals from the sample of the second substrate using the optical system, wherein the system stage includes a plurality of datums, the datums engaging the first substrate and engaging the adapter plate during the positioning and replacing operations.

9. The method of claim 8, wherein the first substrate is slidable within the window along an XY-plane that extends parallel to the inner frame edge and wherein the adapter plate is slidable within the window along the XY-plane.

10. A method comprising:

positioning a first carrier assembly on a system stage, the first carrier assembly including a support frame having an inner frame edge that defines a window of the support frame, the first carrier assembly including a first substrate that is positioned within the window and surrounded by the inner frame edge, the first substrate having a sample thereon that is positioned within an imaging zone of an optical system;

detecting optical signals from the sample of the first substrate using the optical system;

replacing the first carrier assembly with a second carrier assembly on the system stage, the second carrier assembly including a support frame and an adapter plate coupled to the support frame, the second carrier assembly having a second substrate held by the adapter plate that has a sample thereon, the sample of the second substrate being positioned within the imaging zone of an optical system; and

detecting optical signals from the sample of the second substrate using the optical system, wherein the adapter plate includes an inner plate edge that defines a pocket, the second substrate being disposed within the pocket and engaging the plate edge.

11. A method comprising:

positioning a first carrier assembly on a system stage, the first carrier assembly including a support frame having an inner frame edge that defines a window of the support frame, the first carrier assembly including a first substrate that is positioned within the window and surrounded by the inner frame edge, the first substrate having a sample thereon that is positioned within an imaging zone of an optical system;

detecting optical signals from the sample of the first substrate using the optical system;

replacing the first carrier assembly with a second carrier assembly on the system stage, the second carrier assembly including a support frame and an adapter plate coupled to the support frame, the second carrier assembly having a second substrate held by the adapter plate that has a sample thereon, the sample of the second substrate being positioned within the imaging zone of an optical system; and

detecting optical signals from the sample of the second substrate using the optical system, wherein replacing the first carrier assembly with the second carrier assembly includes removing the first substrate from the support frame and positioning the second substrate within the adapter plate.

12. A method comprising:

positioning a first carrier assembly on a system stage, the first carrier assembly including a support frame having an inner frame edge that defines a window of the support frame, the first carrier assembly including a first substrate that is positioned within the window and surrounded by the inner frame edge, the first substrate having a sample thereon that is positioned within an imaging zone of an optical system;

detecting optical signals from the sample of the first substrate using the optical system;

replacing the first carrier assembly with a second carrier assembly on the system stage, the second carrier assembly including a support frame and an adapter plate coupled to the support frame, the second carrier assembly having a second substrate held by the adapter plate that has a sample thereon, the sample of the second substrate being positioned within the imaging zone of an optical system; and

detecting optical signals from the sample of the second substrate using the optical system, wherein the first carrier assembly includes a holding mechanism that includes a movable datum block that is disposed within a portion of the pocket, the method further comprising;

pressing the datum block, positioning the second substrate within the pocket, and releasing the datum block, the datum block engaging the second substrate to hold the second substrate in the pocket.