SYSTEMS, METHODS, AND APPARATUSES TO IMAGE A SAMPLE FOR BIOLOGICAL OR CHEMICAL ANALYSIS

• US 20120270305A1
• Filed: 10/14/2011
• Published: 10/25/2012
• Est. Priority Date: 01/10/2011
• Status: Active Grant

• Current Assignee: Illumina Incorporated
• Original Assignee: Illumina Incorporated
• Inventors: KINDWALL, ALEXANDER P., REED, MARK T., WILLIAMSON, ERIC, CRANE, BRYAN, LEUNG, PATRICK, BUERMANN, DALE, ERIE, Frederick, PRATT, MARK, HARRIS, JASON, CARSON, ANDREW JAMES, HONG, Stanley S., BRYANT, JASON, WANG, MARK, VERKADE, DREW
• Granted Patent: US 8,951,781 B2
• Time in Patent Office: Days
• US Class Current: 435/287.2
• CPC Class Codes: B01L 2200/025 Align devices or objects to ensure defined positions relative to each other
• CPC Class Codes: B01L 2200/027 for microfluidic devices
• CPC Class Codes: B01L 2200/04 Exchange or ejection of cartridges, containers or reservoirs
• CPC Class Codes: B01L 2200/0689 Sealing
• CPC Class Codes: B01L 2300/022 Transponder chips
• CPC Class Codes: B01L 2300/041 Connecting closures to device or container
• CPC Class Codes: B01L 2300/043 Hinged closures
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0877 Flow chambers
• CPC Class Codes: B01L 3/502715 characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• CPC Class Codes: B01L 3/50273 characterised by the means or forces applied to move the fluids micropumps F04B19/006, of the membrane type F04B43/043
• 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 9/527 for microfluidic devices, e.g. used for lab-on-a-chip
• CPC Class Codes: G01N 2021/058 Flat flow cell
• CPC Class Codes: G01N 2035/00435 Refrigerated reagent storage
• CPC Class Codes: G01N 21/05 Flow-through cuvettes G01N21/09 takes precedence; handling fluid samples G01N1/10
• CPC Class Codes: G01N 35/08 using a stream of discrete samples flowing along a tube system, e.g. flow injection analysis
• CPC Class Codes: G01N 35/1002 Reagent dispensers
• CPC Class Codes: G01N 35/1011 Control of the position or alignment of the transfer device
• CPC Class Codes: G01N 35/1065 Multiple transfer devices
• CPC Class Codes: G01N 35/1079 : with means for piercing stoppers or septums
• CPC Class Codes: Y10T 436/25 : including sample preparation

Abstract

A fluidic device holder configured to orient a fluidic device. The device holder includes a support structure configured to receive a fluidic device. The support structure includes a base surface that faces in a direction along the Z-axis and is configured to have the fluidic device positioned thereon. The device holder also includes a plurality of reference surfaces facing in respective directions along an XY-plane. The device holder also includes an alignment assembly having an actuator and a movable locator arm that is operatively coupled to the actuator. The locator arm has an engagement end. The actuator moves the locator arm between retracted and biased positions to move the engagement end away from and toward the reference surfaces. The locator arm is configured to hold the fluidic device against the reference surfaces when the locator arm is in the biased position.

Claims

1. A fluidic device holder configured to orient a fluidic device with respect to mutually perpendicular X, Y, and Z-axes, the device holder comprising:

a support structure configured to receive a fluidic device, the support structure including a base surface that faces in a direction along the Z-axis and is configured to have the fluidic device positioned thereon;

a plurality of reference surfaces facing in respective directions along an XY-plane;

an alignment assembly comprising an actuator and a movable locator arm that is operatively coupled to the actuator, the locator arm having an engagement end, the actuator moving the locator arm between retracted and biased positions to move the engagement end away from and toward the reference surfaces, wherein the locator arm is configured to hold the fluidic device against the reference surfaces when the locator arm is in the biased position.

2. The fluidic device holder of claim 1, wherein the engagement end moves within the XY-plane when the locator arm is moved between the retracted and biased positions.

3. The fluidic device holder of claim 1, wherein the reference surfaces include first and second reference surfaces, the first reference surface stopping movement of the fluidic device in a direction along the X axis and the second reference surface stopping movement of the fluidic device in a direction along the Y axis, the engagement end moving in a direction along the X and Y axes.

4. The fluidic device holder of claim 1, further comprising a removable cover assembly that is operatively coupled to the actuator, the actuator moving the locator arm to the biased position as the cover assembly is mounted over the fluidic device, the actuator moving the locator arm to the retracted position as the cover assembly is demounted from the fluidic device.

5. The fluidic device holder of claim 4, wherein the cover assembly is configured to engage and hold the fluidic device against the base surface.

6. The fluidic device holder of claim 5, wherein the locator arm is configured to hold the device against the reference surfaces in a fixed position along the XY plane before the cover assembly holds the fluidic device against the base surface.

7. The fluidic device holder of claim 1, further comprising a removable cover assembly that includes a flow system having fluidic ports, the fluidic ports configured to engage corresponding inlet and outlet ports of the fluidic device when the cover assembly is mounted over the fluidic device.

8. The fluidic device holder of claim 7, wherein the flow system further comprises a removable fluid storage device, the fluid storage device comprising a tray, and a plurality of component wells in the tray, individual wells of the plurality having an opening at the top of the well.

9. The fluidic device holder of claim 8, wherein the removable fluid storage device is in a fluid storage system, the fluid storage system comprising

(a) an enclosure having a cavity;

(b) a temperature control assembly configured to regulate a temperature within the cavity; and

(c) a fluid removal assembly comprising a gripper for the removable fluid storage device, an elevator mechanism, and an array of sipper tubes,

wherein the elevator mechanism comprises a drive motor configured to move the array of sipper tubes bi-directionally relative to the gripper;

10. The nucleic acid sequencing system of claim 9, wherein the plurality of component wells comprises a well containing a polymerase, a well containing primer nucleic acids, a well containing nucleic acid denaturants, wells containing nucleotides having reversible terminator moieties and fluorescent labels and a well comprising a nucleic acid sample to be sequenced.

11. The nucleic acid sequencing system of claim 9, wherein the opening at the top of the individual component well comprises a rim that projects a distance away from the upper surface of the tray.

12. The nucleic acid sequencing system of claim 9, wherein the fluid storage device further comprises a protective foil covering the opening at the top of individual wells and the sipper tubes are configured to pierce the protective foil.

13. The fluidic device holder of claim 1, wherein the support structure comprises a thermal module having the base surface, the thermal module configured to transfer thermal energy through the base surface.

14. The fluidic device holder of claim 1, wherein the locator arm directly engages a housing of the fluidic device and the reference surfaces directly engage a flow cell that is floatably held by the housing.

15. The fluidic device holder of claim 1, wherein the fluidic device comprises:

a flow cell including inlet and outlet ports and a flow channel extending therebetween, the flow cell configured to hold a sample-of-interest;

a housing having a reception space that is configured to receive the flow cell, the reception space being sized and shaped to permit the flow cell to float relative to the housing when the locator arm is in the retracted position; and

a gasket coupled to the housing, the gasket having inlet and outlet passages and comprising a compressible material, the gasket being positioned relative to the reception space so that the inlet and outlet ports of the flow cell are approximately aligned with the inlet and outlet passages of the gasket, respectively when the locator arm is in the biased position.

16. The fluidic device holder of claim 15, wherein the fluidic device further comprises a cover member that is rotatably coupled to the housing and includes the gasket, the gasket being rotatable about an axis of rotation between a mounted position and a disengaged position, the inlet and outlet passages being approximately aligned with the inlet and outlet ports when the gasket is in the mounted position and when the locator arm is in the biased position.

17. The fluidic device holder of claim 15, wherein the flow cell has a plurality of edges that extend along a cell plane and define a perimeter of the flow cell, the gasket configured to press against one of the edges when the inlet and outlet passages are approximately aligned and when the locator arm is in the biased position, the gasket limiting movement of the flow cell within the reception space along the cell plane.

18. The fluidic device holder of claim 17, wherein the flow cell has first and second cell sides that face in opposite directions, the first and second cell sides extending along the cell plane, wherein the gasket also presses against one of the first and second cell sides thereby limiting movement in a direction that is perpendicular to the cell plane.

19. The fluidic device holder of claim 17, wherein the flow channel comprises an imaging portion and a non-imaging portion, wherein imaging and non-imaging portions are fluidicly joined by a curved portion, the imaging and non-imaging portions extending parallel to each other,

wherein the inlet port is in fluid communication with the imaging portion of the flow channel, and wherein the outlet port is in fluid communication with the non-imaging portion of the flow channel.

20. The fluidic device holder of claim 19, wherein the width of the imaging portion of the flow channel is larger than the width of the non-imaging portion of the flow channel.

21. The fluidic device holder of claim 19, wherein a plurality of DNA clusters is on the surface of the imaging portion of the flow channel.

22. The fluidic device holder of claim 19, wherein the curved portion of the flow channel comprises a tapering portion, an intermediate portion, and a downstream portion,

wherein the tapering portion connects the imaging portion with the intermediate portion, and

wherein the width of the tapering portion reduces in size from the imaging portion of the flow channel to the intermediate portion.

23. The fluidic device holder of claim 19, wherein the surface of the flow channel comprises a transparent material.

24. A method for orienting a sample area with respect to mutually perpendicular X, Y, and Z-axes, the method comprising:

providing an alignment assembly comprising a movable locator arm having an engagement end, the locator arm being movable between retracted and biased positions;

positioning a fluidic device on a base surface that faces in a direction along the Z-axis and between a plurality of reference surfaces that face in respective directions along an XY-plane, the device having a sample area;

moving the locator arm to the biased position, the locator arm pressing the device against the reference surfaces such that the device is held in a fixed position.

25. An optical assembly comprising:

a base plate having a support side and a component-receiving space along the support side, the component-receiving space being at least partially defined by a reference surface;

an optical component having an optical surface that is configured to reflect light or transmit light therethrough; and

a mounting device including a component retainer and a biasing element that is operatively coupled to the retainer, the retainer holding the optical component so that a space portion of the optical surface faces the reference surface and a path portion of the optical surface extends beyond the support side into an optical path, the biasing element providing an alignment force that holds the optical surface against the reference surface.

26. The optical assembly of claim 25, wherein the component-receiving space is a first component-receiving space and the optical assembly comprises a second component-receiving space, the mounting device and the optical component constituting a first optical device located in the first component-receiving space, the optical assembly further comprising a second optical device located in the second component-receiving space.

27. The optical assembly of claim 26, wherein the first optical device comprises an excitation light module, said excitation light module comprising:

a module frame;

first and second semiconductor light sources (SLSs) secured to the module frame and having fixed positions with respect to each other, the first and second SLSs configured to provide different excitation optical signals; and

an optical component secured to the module frame and having a fixed position and predetermined orientation with respect to the first and second SLSs, the optical component permitting the optical signals from the first SLS to transmit therethrough and reflecting the optical signals from the second SLS, the reflected and transmitted optical signals being directed along a common path out of the module frame.

28. An optical imaging system comprising:

an object holder to hold and move an object;

a detector to detect optical signals from the object at a detector surface;

an optical train configured to direct the optical signals onto the detector surface, the optical train having an object plane proximate to the object holder and an image plane proximate to the detector surface, the optical train including a mirror that is rotatable between an imaging position and a focusing position; and

an image analysis module configured to analyze a test image detected at the detector surface when the mirror is in the focusing position, the test image having an optimal degree-of-focus at a focused location in the test image, the focused location in the test image being indicative of a position of the object with respect to the object plane, wherein the object holder is configured to move the object toward the object plane based on the focused location.

29. An optical imaging system comprising:

an object holder to hold and move an object;

a detector to detect optical signals from the object at a detector surface;

an optical train having a plurality of optical components configured to direct the optical signals onto the detector surface, the optical train having an object plane proximate to the object holder and an image plane proximate to the detector surface, wherein the detector or one of the optical components constitutes a movable optical device that is movable between an imaging position and a focusing position;

an actuator operatively coupled the movable optical device, the actuator configured to move the movable optical device between the imaging and focusing positions;

an image analysis module configured to analyze a test image detected at the detector surface when the movable optical device is in the focusing position, the test image having an optimal degree-of-focus at a focused location in the test image, the focused location in the test image being indicative of a position of the object with respect to the object plane, wherein the object holder is configured to move the object toward the object plane based on the focused location.