Microdevices and biosensor cartridges for biological or chemical analysis and systems and methods for the same

• US 9,937,497 B2
• Filed: 07/08/2016
• Issued: 04/10/2018
• Est. Priority Date: 10/27/2010
• Status: Active Grant

• Current Assignee: Illumina Incorporated
• Original Assignee: Illumina Incorporated
• Inventors: Eltoukhy, Helmy A., Khurana, Tarun, Javanmardi, Behnam, Sabounchi, Poorya, Aghababazadeh, Majid
• Primary Examiner(s): Sines, Brian J
• Application Number:
  US15/205,275
• Publication Number:
  US 20160318017A1
• Time in Patent Office: 641 Days
• Field of Search: 422 50, 422 681, 422 81, 422502, 422503, 422504, 422509, 422554, 436 43, 436 63, 436174, 436180, 436177, 436178
• CPC Class Codes: B01L 2200/025 Align devices or objects to ensure defined positions relative to each other
• CPC Class Codes: B01L 2200/04 Exchange or ejection of cartridges, containers or reservoirs
• CPC Class Codes: B01L 2200/082 Handling hazardous material
• CPC Class Codes: B01L 2200/10 Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
• CPC Class Codes: B01L 2200/16 Reagents, handling or storing thereof
• CPC Class Codes: B01L 2300/022 Transponder chips
• CPC Class Codes: B01L 2300/023 Sending and receiving of information, e.g. using bluetooth
• CPC Class Codes: B01L 2300/048 enabling gas exchange, e.g. vents
• CPC Class Codes: B01L 2300/0627 Sensor or part of a sensor is integrated
• CPC Class Codes: B01L 2300/0636 Integrated biosensor, microarrays
• CPC Class Codes: B01L 2300/0645 Electrodes
• CPC Class Codes: B01L 2300/0654 Lenses; Optical fibres
• CPC Class Codes: B01L 2300/0819 Microarrays; Biochips
• CPC Class Codes: B01L 2300/0877 Flow chambers
• CPC Class Codes: B01L 2300/161 Control and use of surface tension forces, e.g. hydrophobic, hydrophilic
• CPC Class Codes: B01L 2300/165 Specific details about hydrophobic, oleophobic surfaces
• CPC Class Codes: B01L 2400/0457 passive flow or gravitation
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 2400/0622 distribution valves, valves having multiple inlets and/or outlets, e.g. metering valves, multi-way valves
• CPC Class Codes: B01L 3/502715 characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• CPC Class Codes: B01L 3/5085 : for multiple samples, e.g. microtitration plates
• 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: C12Q 1/6869 : Methods for sequencing
• CPC Class Codes: C12Q 1/6874 : involving nucleic acid arrays, e.g. sequencing by hybridisation

Abstract

A flow cell including inlet and outlet ports in fluid communication with each other through a flow channel that extends therebetween. The flow channel includes a diffuser region and a field region that is located downstream from the diffuser region. The field region of the flow channel directs fluid along reaction sites where desired reactions occur. The fluid flows through the diffuser region in a first flow direction and through the field region in a second flow direction. The first and second flow directions being substantially perpendicular.

Claims

1. A biosensor cartridge configured to removably engage a bioassay system, the biosensor cartridge comprising:

a flow cell including inlet and outlet ports and a flow channel that extends therebetween, the flow cell also including a substrate field in fluid communication with the flow channel, the substrate field having a plurality of reaction sites distributed along a length and a width of the substrate field, the flow channel forming a common space that extends over the substrate field along the length and the width such that the plurality of reaction sites are exposed to the common space;

an activity detector coupled to the flow cell and including an array of pixels, the pixels configured to detect activity along the substrate field that is indicative of desired reactions;

first and second side surfaces, the first side surface including the inlet and outlet ports, the second side surface comprising electrical contacts that are communicatively coupled to the activity detector.

2. The biosensor cartridge of claim 1, wherein the first side surface is shaped to engage a mating side of the bioassay system to facilitate maintaining an electrical connection between the electrical contacts of the second side surface and corresponding mating contacts of the bioassay system.

3. The biosensor cartridge of claim 2, wherein the flow cell includes a cover wall and wherein the inlet and outlet ports are spaced apart from each other and have a planar engagement area of the cover wall extending therebetween along the first side surface, the engagement area being sized and shaped to engage a thermal element of the bioassay system, the cover wall comprising a thermally-conductive material and having a uniform thickness for the engagement area.

4. The biosensor cartridge of claim 1, wherein the inlet and outlet ports project away from the flow channel in a common direction.

6. The biosensor cartridge of claim 1, wherein the reaction sites are reaction chambers having apertures that open onto the common space of the flow channel such that the reaction chambers are in fluid communication with the flow channel, wherein the pixels are assigned to select reaction chambers such that light emissions detected by the pixels indicate that a desired reaction has occurred at the select reaction chamber, the activity detector including circuitry that receives detection signals from the pixels that are representative of the light emissions detected by the pixels from the select reaction chambers, the circuitry configured to analyze the detection signals and generate detection data based on the detection signals by processing the detection signals in a designated manner.

7. The biosensor cartridge of claim 1, wherein the pixels comprise photodetectors configured to detect light signals generated along the substrate field.

8. A method of sequencing comprising:

providing the biosensor cartridge of claim 1, the reaction sites of the substrate field including a plurality of nucleic acid template strands, the pixels configured to detect light emissions from the substrate field that are indicative of desired reactions;

positioning the biosensor cartridge in a system receptacle of a bioassay system such that the electrical contacts engage mating contacts of the bioassay system;

conducting a plurality of SBS events to grow a complementary strand by incorporating nucleotides along each template strand, wherein each of the plurality of SBS events includes detecting the light emissions from the complementary strand along the substrate field, the light emissions being detected by the pixels; and

communicating detection data to the bioassay system through the electrical contacts, the detection data being based on the light emissions detected by the pixels.

9. The method of claim 8, further comprising fluidically coupling inlet and outlet ports of the flow cell to respective conduits of the bioassay system, wherein conducting the plurality of SBS events includes iteratively flowing a fluid that includes a mixture of different types of nucleotides.

10. The method of claim 8, wherein the pixels are assigned to select reaction sites of the substrate field such that light emissions detected by the pixels indicate that a desired reaction has occurred at the select reaction site, the method further comprising analyzing detection signals from the pixels at the activity detector and generating the detection data based on the detection signals by processing the detection signals in a designated manner.

11. The method of claim 8, wherein the flow channel has a flow cross-section taken perpendicular to a flow direction of the fluid, the flow cross-section having a height that changes along the flow channel to control the flow of the fluid therein.

12. The biosensor cartridge of claim 1, wherein the substrate field includes a planar surface, the reaction sites being portions of the planar surface that are located on the planar surface in a predetermined manner, wherein the pixels are assigned to select reaction sites such that light emissions detected by the pixels indicate that a desired reaction has occurred at the select reaction site, the activity detector including circuitry that receives detection signals from the pixels that are representative of the light emissions detected by the pixels from the select reaction sites, the circuitry configured to analyze the detection signals and generate detection data based on the detection signals by processing the detection signals in a designated manner.

13. The biosensor cartridge of claim 1, wherein the biosensor cartridge is a self-contained, disposable unit having biomolecules immobilized to the reaction sites of the substrate field prior to the biosensor cartridge being used by an assay system.

14. The biosensor cartridge of claim 13, further comprising an identification component that is configured to provide, prior to the biosensor cartridge being used, information for identifying at least one of the biosensor cartridge or the biomolecules immobilized to the reaction sites.

15. The biosensor cartridge of claim 14, wherein the identification component includes at least one of a label or a transmitting device.

16. The biosensor cartridge of claim 13, further comprising circuitry configured to communicate, prior to the biosensor cartridge being used, identification information to a bioassay system, the identification information identifying at least one of the biosensor cartridge or the biomolecules immobilized to the reaction sites.

17. The biosensor cartridge of claim 16, wherein the identification information is communicated through the electrical contacts.

18. The biosensor cartridge of claim 1, wherein the flow cell and the activity detector are coupled to each other as a microdevice, the biosensor cartridge further comprising a cartridge housing that holds the microdevice, the cartridge housing having openings that expose the first and second side surfaces to an exterior of the cartridge housing.

19. The biosensor cartridge of claim 18, wherein the microdevice is floatable within a restricted space relative to the cartridge housing.

5. A biosensor cartridge configured to removably engage a bioassay system, the biosensor cartridge comprising:

a flow cell including inlet and outlet ports and a flow channel that extends therebetween, the flow cell also including a substrate field in fluid communication with the flow channel;

an activity detector coupled to the flow cell and including an array of pixels, the pixels configured to detect activity along the substrate field that is indicative of desired reactions;

first and second side surfaces, the first side surface including the inlet and outlet ports, the second side surface comprising electrical contacts that are communicatively coupled to the activity detector, wherein the first and second side surfaces face in substantially opposite directions.