Cartridges, kits, and methods for amplification and detection of analytes

• US 10,272,434 B2
• Filed: 04/04/2018
• Issued: 04/30/2019
• Est. Priority Date: 03/11/2013
• Status: Active Grant

• Current Assignee: Cue Health Inc.
• Original Assignee: Cue Health Inc.
• Inventors: Khattak, Ayub, Sever, Clinton, Nelson, Paul, Cooper, Ryan, Congdon, Thomas, DeMartino, Justin, Shapiro, Raphael, Duncan, Mark
• Primary Examiner(s): White, Dennis
• Application Number:
  US15/945,646
• Publication Number:
  US 20180229231A1
• Time in Patent Office: 391 Days
• CPC Class Codes: B01F 31/86 with vibration of the receptacle or part of it
• CPC Class Codes: B01L 2200/025 Align devices or objects to ensure defined positions relative to each other
• CPC Class Codes: B01L 2200/026 Fluid interfacing between devices or objects, e.g. connectors, inlet details
• CPC Class Codes: B01L 2200/027 for microfluidic devices
• CPC Class Codes: B01L 2200/028 Modular arrangements
• CPC Class Codes: B01L 2200/0668 Trapping microscopic beads
• CPC Class Codes: B01L 2200/0684 Venting, avoiding backpressure, avoid gas bubbles
• CPC Class Codes: B01L 2200/0689 Sealing
• CPC Class Codes: B01L 2200/087 Ergonomic aspects
• 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 2300/023 Sending and receiving of information, e.g. using bluetooth
• CPC Class Codes: B01L 2300/025 Displaying results or values with integrated means
• CPC Class Codes: B01L 2300/04 Closures and closing means
• CPC Class Codes: B01L 2300/044 pierceable, e.g. films, membranes
• CPC Class Codes: B01L 2300/06 Auxiliary integrated devices, integrated components
• CPC Class Codes: B01L 2300/0627 Sensor or part of a sensor is integrated
• CPC Class Codes: B01L 2300/0645 Electrodes
• CPC Class Codes: B01L 2300/0681 Filter
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0838 : Capillaries
• CPC Class Codes: B01L 2300/0864 : comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
• CPC Class Codes: B01L 2300/0867 : Multiple inlets and one sample wells, e.g. mixing, dilution
• CPC Class Codes: B01L 2300/087 : Multiple sequential chambers
• CPC Class Codes: B01L 2300/12 : Specific details about materials
• CPC Class Codes: B01L 2300/161 : Control and use of surface tension forces, e.g. hydrophobic, hydrophilic
• CPC Class Codes: B01L 2300/1827 : using resistive heater
• CPC Class Codes: B01L 2400/0406 : capillary forces
• CPC Class Codes: B01L 2400/0439 : ultrasonic vibrations, vibrating piezo elements
• CPC Class Codes: B01L 2400/0487 : fluid pressure, pneumatics
• CPC Class Codes: B01L 2400/0677 : phase change valves; Meltable, freezing, dissolvable plugs; Destructible barriers
• CPC Class Codes: B01L 2400/0683 : mechanically breaking a wall or membrane within a channel or chamber
• CPC Class Codes: B01L 3/5027 : by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip B01L3/5023 takes precedence; micromixers B01F33/30; microreactors for synthesis B01J19/0093; microcapillary devices in general B81B1/00
• CPC Class Codes: B01L 3/502715 : characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• CPC Class Codes: B01L 3/502723 : characterised by venting arrangements
• CPC Class Codes: B01L 3/502738 : characterised by integrated valves microvalves F16K99/0001
• CPC Class Codes: B01L 3/5029 : using swabs
• CPC Class Codes: B01L 3/508 : rigid containers not provided for above
• 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: B05D 2518/00 : Other type of polymers
• CPC Class Codes: B05D 3/002 : Pretreatement
• CPC Class Codes: C12Q 1/6825 : Nucleic acid detection involving sensors
• CPC Class Codes: F16K 2099/0084 : Chemistry or biology, e.g. "lab-on-a-chip" technology
• CPC Class Codes: F16K 99/0032 : using phase transition or influencing viscosity
• CPC Class Codes: F16K 99/0036 : operated by temperature variations
• CPC Class Codes: G01N 1/02 : Devices for withdrawing samples sampling of foundation soil E02D1/04; collecting or conveying radioactive samples G01T7/00, e.g. G01T7/02, G01T7/08
• CPC Class Codes: G01N 2001/027 : field kits / quick test kits
• CPC Class Codes: G01N 2001/028 : Sampling from a surface, swabbing, vaporising
• CPC Class Codes: G01N 2035/00277 : Special precautions to avoid contamination (e.g. enclosures, glove- boxes, sealed sample carriers, disposal of contaminated material)
• CPC Class Codes: G01N 2035/00554 : using ultrasound
• CPC Class Codes: G01N 21/78 : producing a change of colour
• CPC Class Codes: G01N 2458/30 : Electrochemically active labels
• CPC Class Codes: G01N 27/28 : Electrolytic cell components
• CPC Class Codes: G01N 27/3271 : Amperometric enzyme electrodes for analytes in body fluids, e.g. glucose in blood amperometry per se G01N27/49; aspects concerning the enzyme reagent C12Q1/001
• CPC Class Codes: G01N 27/3272 : Test elements therefor, i.e. disposable laminated substrates with electrodes, reagent and channels optical biosensors G01N33/52
• CPC Class Codes: G01N 27/3273 : Devices therefor, e.g. test element readers, circuitry details not specific to biochemical electrodes G01N33/4875
• CPC Class Codes: G01N 33/54306 : Solid-phase reaction mechanisms
• CPC Class Codes: G01N 33/54326 : Magnetic particles
• CPC Class Codes: G01N 33/54333 : Modification of conditions of immunological binding reaction, e.g. use of more than one type of particle, use of chemical agents to improve binding, choice of incubation time or application of magnetic field during binding reaction
• CPC Class Codes: G01N 33/54366 : Apparatus specially adapted for solid-phase testing
• CPC Class Codes: G01N 33/54373 : involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings
• CPC Class Codes: G01N 33/581 : with enzyme label (including co-enzymes, co-factors, enzyme inhibitors or substrates)
• CPC Class Codes: G01N 35/00029 : provided with flat sample substrates, e.g. slides G01N35/028 takes precedence
• CPC Class Codes: G01N 35/0098 : involving analyte bound to insoluble magnetic carrier, e.g. using magnetic separation magnetic particles used in immunoassays G01N33/54326; magnetic separation in general B03C
• CPC Class Codes: G01N 35/1095 : for supplying the samples to flow-through analysers for a specific analyser see relevant groups, e.g. under G01N15/00, G01N21/00, G01N27/00, G01N30/00, H01J49/00
• CPC Class Codes: H04M 1/72409 : by interfacing with external accessories hands-free H04M1/60
• CPC Class Codes: H04M 1/72412 : using two-way short-range wireless interfaces
• CPC Class Codes: Y10T 137/1797 : Heat destructible or fusible

Abstract

Devices, systems, and methods for detecting molecules of interest within a collected sample are described herein. In certain embodiments, self-contained sample analysis systems are disclosed, which include a reusable reader component, a disposable cartridge component, and a disposable sample collection component. The reader component may communicate with a remote computing device for the digital transmission of test protocols and test results. In various disclosed embodiments, the systems, components, and methods are configured to identify the presence, absence, and/or quantity of particular nucleic acids, proteins, or other analytes of interest, for example, in order to test for the presence of one or more pathogens or contaminants in a sample.

Claims

1. A sample analysis cartridge comprising:

an input tunnel that extends from an aperture, the input tunnel configured to permit insertion of a sample collection device having a distal portion adapted to be exposed to a sample comprising a target nucleic acid;

a reagent ball comprising reagents for amplification of the target nucleic acid by an amplification reaction;

a reservoir configured to hold a fluid, the reservoir further configured to receive the sample from the sample collection device and to receive the reagent ball such that the sample is mixed with an effective amount of the reagents for amplification of the target nucleic acid in the fluid of the reservoir to generate amplicons comprising signaling agents;

an analysis channel configured to receive the fluid comprising the amplicons from the reservoir; and

a sensor at least partially disposed in the analysis channel such that the amplicons indicative of at least one of a presence, absence, or quantity of the target nucleic acid in the sample localize over the sensor and the sensor senses signals indicative of at least one of the presence, absence, or quantity of the target nucleic acid in the sample based on reactions between a substrate and the signaling agents of the amplicons localized over the sensor.

2. The sample analysis cartridge of claim 1, wherein the reagent ball comprises polymerase, primers for amplification of the target nucleic acid and the signaling agent for the detection of the amplification of the target nucleic acid.

3. The sample analysis cartridge of claim 2, wherein the reagent ball further comprises one or more affinity molecules covalently or non-covalently bound to a solid particle for detection of the target nucleic acid.

4. The sample analysis cartridge of claim 1, wherein the reagent ball is disposed in the input tunnel and not exposed to the fluid in the reservoir in a pre-mixing position, and

wherein the reagent ball is configured to move into the reservoir for mixing with the fluid in the reservoir in a mixing position.

5. The sample analysis cartridge of claim 1, further comprising a shuttle defining a first compartment and a second compartment, the first and second compartments configured to be disposed within the reservoir in a mixing position.

6. The sample analysis cartridge of claim 5, wherein the shuttle is configured to move within the input tunnel such that the first and second compartments are not exposed to the fluid in the reservoir in a pre-mixing position.

7. The sample analysis cartridge of claim 5, further comprising a piezoelectric transducer configured to emit energy into the reservoir to move the fluid in the reservoir between the first and second compartments to mix the fluid, the sample, and the reagents in the reservoir.

8. The sample analysis cartridge of claim 5, wherein the first compartment comprises a reagent ball compartment configured to house the reagent ball and the second compartment comprises a sample compartment configured to receive the sample from the sample collection device.

9. The sample analysis cartridge of claim 1, further comprising a temperature sensor configured to sense temperature indicative of temperature of the fluid in the reservoir.

10. The sample analysis cartridge of claim 9, wherein the temperature sensor is disposed on a printed circuit board positioned adjacent to a piezoelectric transducer.

11. The sample analysis cartridge of claim 10, wherein the piezoelectric transducer is configured to emit energy into the reservoir to move the fluid in the reservoir to mix the fluid, the sample, and the reagents in the reservoir and to emit the energy in a modified manner based on the sensed temperature.

12. The sample analysis cartridge of claim 11, wherein the energy emitted by the piezoelectric transducer is configured to cause the amplification reaction to cure on the target nucleic acid.

13. The sample analysis cartridge of claim 1, further comprising a contact switch configured to indicate insertion of the sample collection device in the input tunnel.

14. The sample analysis cartridge of claim 1, wherein the reagent ball further comprises magnetic particles configured to be magnetically held over a target working electrode of the sensor.

15. The sample analysis cartridge of claim 1, further comprising a substrate reservoir configured to hold a substrate solution comprising the substrate, the substrate reservoir comprising an outlet configured to permit the substrate solution to travel therethrough and into the analysis channel to at least the portion of the sensor such that the substrate reacts with signaling agents localized over the sensor.

16. A sample analysis cartridge comprising:

an input tunnel that extends from an aperture, the input tunnel configured to permit insertion of a sample collection device having a distal portion adapted to be exposed to a sample comprising a target nucleic acid;

a reservoir configured to hold a fluid, the reservoir further configured to receive the sample from the sample collection device such that the sample is mixed with an effective amount of reagents for amplification of the target nucleic acid in the fluid of the reservoir to generate amplicons comprising signaling agents;

a shuttle defining a first compartment and a second compartment, the first and second compartments configured to be disposed within the reservoir in a mixing position;

an analysis channel configured to receive the fluid comprising the amplicons from the reservoir; and

a sensor at least partially disposed in the analysis channel such that the amplicons indicative of at least one of a presence, absence, or quantity of the target nucleic acid in the sample localize over the sensor and the sensor senses signals indicative of at least one of the presence, absence, or quantity of the target nucleic acid in the sample based on reactions between a substrate and the signaling agents of the amplicons localized over the sensor.

17. The sample analysis cartridge of claim 16, further comprising a reagent ball comprising the reagents for amplification of the target nucleic acid by an amplification reaction.

18. The sample analysis cartridge of claim 17, wherein the reagent ball comprises polymerase, primers for amplification of the target nucleic acid and the signaling agent for the detection of the amplification of the target nucleic acid.

19. The sample analysis cartridge of claim 18, wherein the reagent ball further comprises one or more affinity molecules covalently or non-covalently bound to a solid particle for detection of the target nucleic acid.

20. The sample analysis cartridge of claim 17, wherein the reagent ball is disposed in the input tunnel and not exposed to the fluid in the reservoir in a pre-mixing position, and

wherein the reagent ball is configured to move into the reservoir for mixing with the fluid in the reservoir in a mixing position.

21. The sample analysis cartridge of claim 16, wherein the shuttle is configured to move within the input tunnel such that the first and second compartments are not exposed to the fluid in the reservoir in a pre-mixing position.

22. The sample analysis cartridge of claim 16, further comprising a piezoelectric transducer configured to emit energy into the reservoir to move the fluid in the reservoir between the first and second compartments to mix the fluid, the sample, and the reagents in the reservoir.

23. The sample analysis cartridge of claim 16, wherein the first compartment comprises a reagent ball compartment configured to house a reagent ball comprising the reagents for amplification of the target nucleic acid by an amplification reaction and the second compartment comprises a sample compartment configured to receive the sample from the sample collection device.

24. The sample analysis cartridge of claim 16, further comprising a temperature sensor configured to sense temperature indicative of temperature of the fluid in the reservoir.

25. The sample analysis cartridge of claim 24, wherein the temperature sensor is disposed on a printed circuit board positioned adjacent to a piezoelectric transducer.

26. The sample analysis cartridge of claim 25, wherein the piezoelectric transducer is configured to emit energy into the reservoir to move the fluid in the reservoir to mix the fluid, the sample, and the reagents in the reservoir and to emit the energy in a modified manner based on the sensed temperature.

27. The sample analysis cartridge of claim 26, wherein the energy emitted by the piezoelectric transducer is configured to cause an amplification reaction to cure on the target nucleic acid.

28. The sample analysis cartridge of claim 16, further comprising a contact switch configured to indicate insertion of the sample collection device in the input tunnel.

29. The sample analysis cartridge of claim 16, further comprising a reagent ball comprising the reagents for amplification of the target nucleic acid by an amplification reaction, the reagent ball further comprising magnetic particles configured to be magnetically held over a target working electrode of the sensor.

30. The sample analysis cartridge of claim 16, further comprising a substrate reservoir configured to hold a substrate solution comprising the substrate, the substrate reservoir comprising an outlet configured to permit the substrate solution to travel therethrough and into the analysis channel to at least the portion of the sensor such that the substrate reacts with signaling agents localized over the sensor.