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

• US 10,406,519 B2
• Filed: 03/26/2018
• Issued: 09/10/2019
• 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:
  US15/936,165
• Publication Number:
  US 20180214871A1
• Time in Patent Office: 533 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 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.

2. The biosensor cartridge of claim 1, wherein the substrate field includes a plurality of separate reaction sites having corresponding nucleic acids.

3. The biosensor cartridge of claim 2, wherein the reaction sites include recesses disposed along the substrate layer that open to the flow channel.

4. The biosensor cartridge of claim 2, 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.

5. The biosensor cartridge of claim 1, 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.

6. The biosensor cartridge of claim 1, 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.

7. The biosensor cartridge of claim 1, 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.

8. The biosensor cartridge of claim 1, wherein the activity detector and the substrate layer are attached to each other through an intermediate layer that permits the pixels to detect the activity indicative of the desired reaction.

9. The biosensor cartridge of claim 2, wherein in the substrate layer has a fixed position relative to the activity detector such that the reaction sites have known spatial locations relative to at least one predetermined pixel.

10. The biosensor cartridge of claim 1, wherein the activity detector includes circuitry that is for at least one of amplification, digitization, storage, and processing of the detected activity.

11. The biosensor cartridge of claim 1, wherein the electrical contacts comprise contact pads to engage the corresponding mating contacts of the bioassay system.

12. The biosensor cartridge of claim 1, wherein the second side surface includes respective openings to the inlet and outlet ports, the openings to removably engage nozzles of the bioassay system to fluidicly couple the flow channel to the bioassay system.

13. The biosensor cartridge of claim 12, wherein the first side surface faces in a mating direction, the second side surface receiving the nozzles through the corresponding openings of the inlet and outlet ports when the nozzles approach the second side surface in the mating direction, wherein the electrical contacts of the first side surface are pressed against corresponding mating contacts of the bioassay system when the nozzles engage the corresponding inlet and outlet ports.

14. The biosensor cartridge of claim 1, wherein the second side surface includes an engagement area that extends along and proximate to the flow channel, the engagement area being sized and shaped to interface with a thermal element of the bioassay system.

15. The biosensor cartridge of claim 14, wherein the first side surface faces in a mating direction, the second side surface receiving the thermal element when the thermal element approaches the engagement area in the mating direction, wherein the electrical contacts of the first side surface are pressed against corresponding mating contacts of the bioassay system when the thermal element interfaces with the engagement area.

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

17. The biosensor cartridge of claim 1, wherein the flow channel includes inlet and outlet channel portions that extend from the respective openings of the inlet and outlet ports and a field channel portion that extends along the substrate field, wherein the inlet and outlet channel portions extend parallel to a port plane and the field channel portion extends parallel to a channel plane, the channel and port planes being substantially perpendicular to one another.

18. The biosensor cartridge of claim 1, further comprising an identification component to provide identification information to the bioassay system, the identification information relating to the biosensor cartridge.

19. The biosensor cartridge of claim 18, wherein the identification component comprises an RFID tag.

20. The biosensor cartridge of claim 18, wherein the identification component communicates to the bioassay system through the electrical contacts.