Integrated optoelectronic read head and fluidic cartridge useful for nucleic acid sequencing

• US 10,549,281 B2
• Filed: 05/12/2017
• Issued: 02/04/2020
• Est. Priority Date: 04/03/2012
• Status: Active Grant

• Current Assignee: Illumina Incorporated
• Original Assignee: Illumina Incorporated
• Inventors: Buermann, Dale, Moon, John A., Crane, Bryan, Wang, Mark, Hong, Stanley S., Harris, Jason, Hage, Matthew, Nibbe, Mark J.
• Primary Examiner(s): Crow, Robert T.
• Application Number:
  US15/594,413
• Publication Number:
  US 20170246635A1
• Time in Patent Office: 998 Days
• Field of Search: None
• CPC Class Codes: B01L 2200/16 Reagents, handling or storing thereof
• CPC Class Codes: B01L 2300/0877 Flow chambers
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 2400/06 Valves, specific forms thereof
• CPC Class Codes: B01L 3/502715 characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• CPC Class Codes: B01L 3/527 for a plurality of reagents
• CPC Class Codes: C12Q 1/6869 Methods for sequencing
• CPC Class Codes: C12Q 1/6874 involving nucleic acid arrays, e.g. sequencing by hybridisation
• CPC Class Codes: G01N 2021/0307 Insert part in cell
• CPC Class Codes: G01N 2021/0325 Cells for testing reactions, e.g. containing reagents
• CPC Class Codes: G01N 2021/058 Flat flow cell
• CPC Class Codes: G01N 2021/6417 Spectrofluorimetric devices
• CPC Class Codes: G01N 2021/6441 with two or more labels
• CPC Class Codes: G01N 2021/6482 Sample cells, cuvettes
• CPC Class Codes: G01N 21/6428 Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" in vivo A61B5/00; immunoassay G01N33/53
• CPC Class Codes: G01N 21/6456 Spatial resolved fluorescence measurements; Imaging
• CPC Class Codes: G01N 21/6486 Measuring fluorescence of biological material, e.g. DNA, RNA, cells G01N21/6428 takes precedence

Abstract

A detection apparatus having a read head including a plurality of microfluorometers positioned to simultaneously acquire a plurality of the wide-field images in a common plane; and (b) a translation stage configured to move the read head along a substrate that is in the common plane. The substrate can be a flow cell that is included in a cartridge, the cartridge also including a housing for (i) a sample reservoir; (ii) a fluidic line between the sample reservoir and the flow cell; (iii) several reagent reservoirs in fluid communication with the flow cell, (iv) at least one valve configured to mediate fluid communication between the reservoirs and the flow cell; and (v) at least one pressure source configured to move liquids from the reservoirs to the flow cell. The detection apparatus and cartridge can be used together or independent of each other.

Claims

1. A fluidics cartridge, comprising:

a flow cell comprising an optically transparent surface, an inlet, an outlet, and a plurality of lanes; and

a housing comprising a material that is optically opaque, wherein the housing holds;

a plurality of sample reservoirs;

a common reagent reservoir;

a rotary valve including a plurality of sample input ports in respective fluid communication with a corresponding sample reservoir of the plurality of sample reservoirs, a common reagent reservoir input port in fluid communication with the common reagent reservoir, and a plurality of output ports in respective fluid communication with the plurality of lanes of the flow cell through individual fluid lines, the rotary valve having a first position to allow liquid flow from the common reagent reservoir to the plurality of lanes of the flow cell through the plurality of output ports and to restrict liquid flow from the plurality of samples reservoirs, and having a second position to allow liquid flow from each of the plurality of sample reservoirs to a corresponding lane of the plurality of lanes of the flow cell through the plurality of output ports and to restrict liquid flow from the common reagent reservoir; and

at least one pressure source to move liquids from the plurality of sample reservoirs or the common reagent reservoir to the flow cell via the inlet of the flow cell;

wherein an optically transparent window interrupts the housing, and wherein the flow cell is positioned in the optically transparent window.

2. The fluidics cartridge as defined in claim 1 wherein the housing includes a reception area sized to hold the flow cell by a compression fit.

3. The fluidics cartridge as defined in claim 1 wherein the housing includes a reception area sized to hold the flow cell and permit the flow cell to float relative to the housing.

4. The fluidics cartridge as defined in claim 1, further comprising an other valve connected to the outlet of the flow cell, and wherein:

the at least one pressure source includes a plurality of pumps; and

each of the plurality of lanes is respectively fluidically connected to one of the plurality of the pumps through the other valve.

5. The fluidics cartridge as defined in claim 4, further comprising a waste reservoir fluidically connected to the other valve.

6. The fluidics cartridge as defined in claim 1, further comprising a wash reservoir fluidically connected to the rotary valve.

7. The fluidics cartridge as defined in claim 1, further comprising a plurality of supplemental reservoirs fluidically connected to the flow cell via the inlet of the flow cell, and wherein:

the at least one pressure source is a pump having a reverse direction to move used liquids from the flow cell to the plurality of supplemental reservoirs; and

the rotary valve has different ports to respectively direct the used liquids to the plurality of supplemental reservoirs.

8. A fluidics cartridge, comprising:

a flow cell comprising an optically transparent surface, an inlet port, an outlet port, and a plurality of lanes; and

a housing comprising a material that is optically opaque, wherein the housing holds;

a plurality of sample reservoirs;

a common reagent reservoir in fluid communication with the flow cell via the inlet port of the flow cell and via the outlet port of the flow cell;

a rotary valve including a plurality of sample input ports in respective fluid communication with a corresponding sample reservoir of the plurality of sample reservoirs, a common reagent reservoir input port in fluid communication with the common reagent reservoir, and a plurality of output ports in respective fluid communication with the plurality of lanes of the flow cell through individual fluid lines, the rotary valve having a first position to allow liquid flow from the common reagent reservoir to the plurality of lanes of the flow cell through the plurality of output ports and to restrict liquid flow from the plurality of samples reservoirs, and having a second position to allow liquid flow from each of the plurality of sample reservoirs to a corresponding lane of the plurality of lanes of the flow cell through the plurality of output ports and to restrict liquid flow from the common reagent reservoir;

a pump positioned downstream of the flow cell and upstream of a second valve, wherein the pump is a pressure source to move liquids from the plurality of sample reservoirs or the common reagent reservoir to the flow cell via the inlet port of the flow cell; and

the second valve to control fluid flow from the flow cell to the common reagent reservoir;

wherein an optically transparent window interrupts the housing, and wherein the flow cell is positioned in the optically transparent window.

9. The fluidics cartridge as defined in claim 8, further comprising:

a first fluidic line connecting the common reservoir to the rotary valve;

a second fluidic line connecting the outlet port of the flow cell to the pump;

a third fluidic line connecting the pump to the second valve; and

a fourth fluidic line connecting the common reagent reservoir to the second valve.

10. The fluidics cartridge as defined in claim 9, further comprising:

a waste reservoir; and

a fifth fluidic line connecting the waste reservoir to the second valve.

11. A fluidics cartridge, comprising:

a flow cell comprising an optically transparent surface, an inlet port, an outlet port, and a plurality of lanes; and

a housing comprising a material that is optically opaque, wherein the housing holds;

a plurality of sample reservoirs;

a common reagent reservoir in fluid communication with the flow cell via the inlet port of the flow cell;

a plurality of supplemental reservoirs in fluid communication with the flow cell via the outlet port of the flow cell;

a first rotary valve including a plurality of sample input ports in respective fluid communication with a corresponding sample reservoir of the plurality of sample reservoirs, a common reagent reservoir input port in fluid communication with the common reagent reservoir, and a plurality of output ports in respective fluid communication with the plurality of lanes of the flow cell through individual fluid lines, the first rotary valve having a first position to allow liquid flow from the common reagent reservoir to the plurality of lanes of the flow cell through the plurality of output ports and to restrict liquid flow from the plurality of samples reservoirs, and having a second position to allow liquid flow from each of the plurality of sample reservoirs to a corresponding lane of the plurality of lanes of the flow cell through the plurality of output ports and to restrict liquid flow from the common reagent reservoir;

a second valve connected to each of the plurality of supplemental reservoirs and to the outlet port of the flow cell; and

a pump positioned downstream of the flow cell and upstream of the second valve, wherein the pump is a pressure source to move liquids from the plurality of sample reservoirs or the common reagent reservoir to the flow cell via the inlet port of the flow cell;

wherein an optically transparent window interrupts the housing, and wherein the flow cell is positioned in the optically transparent window.

12. The fluidics cartridge as defined in claim 11, further comprising:

a first fluidic line connecting the reagent reservoir to the first rotary valve;

a second fluidic line connecting the outlet port of the flow cell to the pump;

a third fluidic line connecting the pump to the second valve; and

fourth fluidic lines respectively connecting each of the plurality of supplemental reservoirs to the second valve.

13. The fluidics cartridge as defined in claim 12, further comprising:

a waste reservoir; and

a fifth fluidic line connecting the waste reservoir to the second valve.

14. The fluidics cartridge as defined in claim 11 wherein:

the plurality of supplemental reservoirs are fluidically connected to the first rotary valve; and

the first rotary valve includes dedicated ports to deliver used liquids from each of the plurality of supplemental reservoirs to the flow cell.

15. The fluidics cartridge as defined in claim 11, further comprising a third valve fluidically connected to the plurality of supplemental reservoirs to respectively deliver used liquids from each of the plurality of supplemental reservoirs to the flow cell.