Systems and methods for detection and quantification of analytes

• US 9,522,397 B2
• Filed: 11/30/2015
• Issued: 12/20/2016
• Est. Priority Date: 03/11/2013
• Status: Active Grant

• Current Assignee: Cue Health Inc.
• Original Assignee: Cue, Inc. (Cue Health Inc.)
• Inventors: Khattak, Ayub, Sever, Clinton
• Primary Examiner(s): WHITE, DENNIS MICHAEL
• Application Number:
  US14/954,817
• Publication Number:
  US 20160091518A1
• Time in Patent Office: 386 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 2200/026 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 2200/04 Exchange or ejection of cartridges, containers or reservoirs
• 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 2400/0487 : 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: 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 2035/00564 : Handling or washing solid phase elements, e.g. beads
• 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 33/5438 : Electrodes
• 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 35/08 : using a stream of discrete samples flowing along a tube system, e.g. flow injection analysis
• 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. In some embodiments, the reader component communicates 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 cartridge comprising:

an input tunnel configured to permit full or partial insertion of a sample collection device adapted to be exposed to a sample;

a sample reservoir configured to hold a fluid and configured to receive the sample from the sample collection device such that the sample and reagents mix in the fluid;

a chemical substrate reservoir configured to hold a substrate solution comprising a chemical substrate, the chemical substrate reservoir fluidicly isolated from the sample reservoir;

an analysis channel configured to receive, from the sample reservoir, the fluid comprising the sample and the reagents mixed therein, the analysis channel further configured to receive, from the chemical substrate reservoir, the substrate solution comprising the chemical substrate; and

a sensor at least partially disposed within the analysis channel, the sensor configured to be exposed to the fluid comprising the sample and the reagents mixed therein from the sample reservoir in the analysis channel such that the reagents indicative of at least one of a presence, absence, or quantity of one or more analytes within the sample localize over the sensor, the sensor further configured to be exposed to the substrate solution comprising the chemical substrate from the chemical substrate reservoir such that the sensor generates an electrical signal indicative of at least one of the presence, absence, or quantity of the one or more analytes within the sample based on reactions between the chemical substrate and the reagents localized at the sensor within the analysis channel.

2. The cartridge of claim 1, wherein the reagents comprise:

a plurality of magnetic particles having surface-bound affinity molecules;

a plurality of detector agents comprising a plurality of signaling agents selected to react with the chemical substrate; and

a plurality of agents to facilitate access to the one or more analytes and binding between the one or more analytes and the surface-bound affinity molecules and the detector agents.

3. The cartridge of claim 2, wherein the plurality of magnetic particles comprises magnetic particles of two or more sizes, and wherein each size has a different surface-bound affinity molecule for binding to a different analyte of the one or more analytes.

4. The cartridge of claim 1, wherein the fluid comprising the sample and the reagents mixed therein from the sample reservoir comprises a plurality of sandwich complexes formed of the one or more analytes bound to both a surface affinity molecule on a surface of a magnetic particle and a detector agent.

5. The cartridge of claim 4, wherein the electrical signal comprises information in a quantity proportional to a quantity of the one or more analytes present within the sample localized at the sensor.

6. The cartridge of claim 1, wherein the fluid comprising the sample and the reagents mixed therein from the sample reservoir comprises a plurality of molecule complexes each formed of a competitive binding agent bound to a surface affinity molecule on a surface of a magnetic particle.

7. The cartridge of claim 6, wherein the electrical signal comprises information in a quantity inversely proportional to a quantity of the one or more analytes present within the sample localized at the sensor.

8. The cartridge of claim 1, wherein the reagents comprise one or magnetic particles directly or indirectly bound to one or more detector agents.

9. The cartridge of claim 8, wherein the sensor is configured to sense the reaction between the chemical substrate and the one or more detector agents directly or indirectly bound to the one or more magnetic particles localized at the sensor.

10. The cartridge of claim 1, wherein the sensor comprises a working electrode, wherein the sensor is configured to generate the electrical signal based on a flow of electrons from the working electrode caused by the reactions between the chemical substrate and the reagents localized at the sensor within the analysis channel.

11. The cartridge of claim 1, further comprising a wash reservoir configured to hold a wash solution, wherein the analysis channel is configured to receive, from the wash reservoir, the wash solution.

12. The cartridge of claim 11, further comprising a first valve positioned between the sample reservoir and the analysis channel, a second valve positioned between the chemical substrate reservoir and the analysis channel, and a third valve positioned between the wash reservoir and the analysis channel.

13. The cartridge of claim 12, wherein each of the first, second, and third valves is phase-changeable upon the application of heat.

14. The cartridge of claim 13, further comprising a plurality of vias aligned with the first, second, and third valves, the plurality of vias configured to heat the first, second, and third valves.

15. The cartridge of claim 1, further comprising a valve positioned between the sample reservoir and the analysis channel.

16. The cartridge of claim 15, wherein the valve is phase-changeable upon the application of heat to permit the fluid comprising the sample and the reagents mixed therein in the sample reservoir to enter the analysis channel.

17. The cartridge of claim 1, further comprising an internal component configured to at least partially define the input tunnel, the sample reservoir, and the analysis channel.

18. The cartridge of claim 1, wherein the sensor comprises a working electrode and a reference electrode.

19. The cartridge of claim 1, further comprising one or more additional sensors at least partially disposed within the analysis channel.

20. The cartridge of claim 1, further comprising a housing configured to house the input tunnel, the sample reservoir, the analysis channel, and the sensor.

21. The cartridge of claim 1, further comprising a sonicator configured to emit energy into the sample reservoir to further mix the sample and the reagents within the fluid in the sample reservoir.

22. The cartridge of claim 1, further comprising one or more locking features that restrict axial or longitudinal movement, or both, of the sample collection device within the input tunnel.

23. The cartridge of claim 22, wherein the one or more locking features comprise at least one of:

one or more positive grooves radially placed in the input tunnel, one or more negative grooves radially placed in the input tunnel, or one or more non-radial engagement features.

24. The cartridge of claim 1, wherein the cartridge is configured to be electrically coupled to a reader.

25. The cartridge of claim 24, wherein the cartridge is configured to transmit the electrical signal indicative of at least one of the presence, absence, or quantity of the one or more analytes within the sample to the reader for processing.

26. A kit comprising:

the cartridge of claim 1; and

the sample collection device.

27. The kit of claim 26, further comprising a reader configured to be electrically coupled to the cartridge, the reader configured to receive and process the electrical signal indicative of at least one of the presence, absence, or quantity of the one or more analytes within the sample.