MICRODEVICES AND BIOSENSOR CARTRIDGES FOR BIOLOGICAL OR CHEMICAL ANALYSIS AND SYSTEMS AND METHODS FOR THE SAME

• US 20160318017A1
• Filed: 07/08/2016
• Published: 11/03/2016
• 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
• Granted Patent: US 9,937,497 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• 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. (canceled)

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

a flow cell having inlet and outlet ports and a flow channel that extends between the inlet and outlet ports, the flow cell including a substrate layer and a flow cover mounted over the substrate layer with the flow channel therebetween, the substrate layer having a substrate field in fluid communication with the flow channel, the substrate field including nucleic acids therealong for conducting a nucleic acid sequencing protocol;

an activity detector secured to the flow cell to form a unitary structure, the activity detector including an array of pixels, the substrate layer having a thickness that extends between the flow channel and the activity detector, the pixels configured to detect light emissions that propagate through the substrate layer and are indicative of desired reactions along the substrate field; and

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.

3. The biosensor cartridge of claim 2, wherein the substrate field includes a plurality of separate reaction sites having corresponding nucleic acids.

4. The biosensor cartridge of claim 3, wherein the reaction sites include recesses disposed along the substrate layer that open to the flow channel.

5. The biosensor cartridge of claim 3, wherein the reaction sites are arranged in a designated array, the corresponding nucleic acids being immobilized to surfaces of the corresponding reaction sites, the corresponding nucleic acids being sequencing primers.

6. The biosensor cartridge of claim 2, 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 and automatically associates detection signals provided by the pixels, the detection signals being representative of the light emissions detected by the corresponding pixels from the select reaction sites.

7. The biosensor cartridge of claim 2, 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.

8. The biosensor cartridge of claim 2, 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 automatically modify values of the light emissions derived from the detection signals by weighting the values.

9. 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.

10. The biosensor cartridge of claim 9, wherein the activity detector comprises a microcircuit arrangement that communicatively couples the pixels to the electrical contacts, the microcircuit arrangement comprising kernels that are each associated with designated pixels, each kernel processing the detected activity from the designated pixels.

11. The biosensor cartridge of claim 9, 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.

12. The biosensor cartridge of claim 11, wherein the inlet and outlet ports are spaced apart from each other and have an engagement area extending therebetween along the first side surface, the engagement area being sized and shaped to engage a thermal element of the bioassay system.

13. The biosensor cartridge of claim 9, wherein the inlet and outlet ports project away from the flow channel in a common direction.

14. The biosensor cartridge of claim 9, wherein the first and second side surfaces face in substantially opposite directions.

15. The biosensor cartridge of claim 9, wherein the substrate field includes a plurality of reaction chambers, the reaction chambers having apertures that open onto the flow channel such that the reaction chambers are in fluid communication with the flow channel.

16. The biosensor cartridge of claim 9, wherein the pixels comprise photodetectors configured to detect light signals generated along the substrate field.

17. A method of sequencing comprising:

providing a biosensor cartridge having a flow cell including a substrate field in fluid communication with a flow channel of the flow cell, the substrate field including a plurality of nucleic acid template strands located therealong, the biosensor cartridge also including an activity detector coupled to the flow cell and including an array of pixels, the pixels configured to detect light emissions from the substrate field that are indicative of desired reactions, the biosensor cartridge also having an exterior side surface that includes a plurality of electrical contacts thereon that are communicatively coupled to the pixels;

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.

18. The method of claim 17, further comprising fluidically coupling the 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.

19. The method of claim 17, 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.

20. The method of claim 17, wherein the biosensor cartridge is a self-contained, disposable unit.

21. The method of claim 17, 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.