Systems and methods for detection and quantification of analytes

• US 9,052,275 B2
• Filed: 11/17/2014
• Issued: 06/09/2015
• 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): DIETERLE, JENNIFER M
• Application Number:
  US14/543,842
• Publication Number:
  US 20150068894A1
• Time in Patent Office: 204 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 sample analysis cartridge, comprising:

a housing having internal barriers defining;

a plurality of reservoirs, an analysis channel, and an input tunnel,

wherein the plurality of reservoirs comprise a first reservoir at least partially filled with a first liquid volume comprising sample preparation reagents, a second reservoir at least partially filled with a second liquid volume comprising a wash solution, and a third reservoir at least partially filled with a third liquid volume comprising a chemical substrate,

wherein each of the first, second, and third reservoirs is, at least at times, in fluid communication with the analysis channel, and

wherein the input tunnel extends from an aperture at a surface of the housing to the first reservoir; and

a circuit board coupled to the housing, the circuit board comprising an electrochemical sensor disposed within a portion of the analysis channel,

wherein the housing is configured to enclose an internal component and the circuit board, the internal component is disposed on or under the circuit board, features of the internal component and the circuit board define the analysis channel, and features of the internal component define the plurality of reservoirs.

2. The sample analysis cartridge of claim 1, further comprising a plurality of valves corresponding with the plurality of reservoirs, wherein a valve is positioned at each intersection between one of the plurality of reservoirs and the analysis channel.

3. The sample analysis cartridge of claim 2, wherein each of the plurality of valves comprises:

a phase-changeable material configured to change phases upon the application of heat, and a via positioned on the circuit board and aligned with the phase-changeable material, the via being thermally coupled to a heating element.

4. The sample analysis cartridge of claim 1, further comprising an absorbent material positioned within the housing at a downstream end of the analysis channel.

5. The sample analysis cartridge of claim 1, wherein the plurality of reservoirs are in a linear formation.

6. The sample analysis cartridge of claim 1, wherein the plurality of reservoirs are in a non-linear formation.

7. The sample analysis cartridge of claim 1, wherein the housing comprises a first cover component and a second cover component, which together enclose the internal component and the circuit board.

8. The sample analysis cartridge of claim 1, further comprising a membrane spanning a cross-sectional area between the input tunnel and the first reservoir.

9. The sample analysis cartridge of claim 1, further comprising a sonication component comprising a piezoelectric element, the sonication component aligned with the first reservoir and configured to generate a signal for detection of:

flex in the first reservoir, a change in a return sound wave, or a shift in a resonance frequency of the piezoelectric element upon entry of a sample collection device into the first reservoir.

10. The sample analysis cartridge of claim 1, wherein the sample preparation reagents comprise a plurality of magnetic particles, each magnetic particle having a surface-bound affinity molecule configured to bind to a target analyte.

11. The sample analysis cartridge of claim 10, wherein the plurality of magnetic particles comprise magnetic particles of at least two sizes, and wherein each size of the magnetic particles has a different surface-bound affinity molecule configured to bind to a different target analyte.

12. The sample analysis cartridge of claim 10, wherein the sample preparation reagents further comprise:

a plurality of detector agents; and

a plurality of agents that facilitate binding between the target analytes, the surface-bound affinity molecules, and the detector agents within the first reservoir.

13. The sample analysis cartridge of claim 12, wherein the detector agents comprise oxidizing enzymes for oxidizing the chemical substrate of the third reservoir.

14. The sample analysis cartridge of claim 10, further comprising a membrane spanning a cross-sectional area between the input tunnel and the first reservoir, wherein a plurality of competitive binding agents are dry-stored on or in the membrane, each competitive binding agent comprising a pre-bound target analyte bound to a signaling agent, and wherein the sample preparation reagents in the first reservoir further comprise a plurality of agents that facilitate binding of:

the surface-bound affinity molecules to the target analytes, and the surface-bound affinity molecules to the competitive binding agents.

15. The sample analysis cartridge of claim 14, wherein the signaling agent comprises an oxidizing enzyme for oxidizing the chemical substrate.

16. The sample analysis cartridge of claim 1, wherein the housing defines a self-contained unit configured to store, during and after analyte detection, all collected sample, liquids, and reagents needed to detect a target analyte.

17. A kit comprising:

the sample analysis cartridge of claim 1; and

a sample collection device sized to fit at least partially within the input tunnel.

18. The kit of claim 17, wherein the sample collection device is configured to retain a biological sample collected from blood, urine, inside a mouth, or inside a nose.

19. The kit of claim 17, wherein the input tunnel and the sample collection device have complementary locking features configured to securely lock the sample collection device in place within the input tunnel.

20. The kit of claim 17, wherein the sample collection device is sized and configured to form a liquid-tight seal with the input tunnel.

21. A sample analysis cartridge, comprising:

a housing having internal barriers defining;

a plurality of reservoirs, an analysis channel, and an input tunnel,

wherein the plurality of reservoirs comprise a first reservoir at least partially filled with a first liquid volume comprising sample preparation reagents, a second reservoir at least partially filled with a second liquid volume comprising a wash solution, and a third reservoir at least partially filled with a third liquid volume comprising a chemical substrate, wherein the sample preparation reagents comprise a plurality of magnetic particles, each magnetic particle having a surface-bound affinity molecule configured to bind to a target analyte,

wherein each of the first, second, and third reservoirs is, at least at times, in fluid communication with the analysis channel, and

wherein the input tunnel extends from an aperture at a surface of the housing to the first reservoir;

a circuit board coupled to the housing, the circuit board comprising an electrochemical sensor disposed within a portion of the analysis channel; and

a membrane configured to span a cross-sectional area between the input tunnel and the first reservoir, wherein a plurality of competitive binding agents are dry-stored on or in the membrane, each competitive binding agent comprising a pre-bound target analyte bound to a signaling agent, and wherein the sample preparation reagents in the first reservoir further comprise a plurality of agents that facilitate binding of;

the surface-bound affinity molecules to the target analytes, and the surface-bound affinity molecules to the competitive binding agents.

22. The sample analysis cartridge of claim 21, further comprising a plurality of valves corresponding with the plurality of reservoirs, wherein a valve is positioned at each intersection between one of the plurality of reservoirs and the analysis channel.

23. The sample analysis cartridge of claim 22, wherein each of the plurality of valves comprises:

a phase-changeable material configured to change phases upon the application of heat, and a via positioned on the circuit board and aligned with the phase-changeable material, the via being thermally coupled to a heating element.

24. The sample analysis cartridge of claim 21, further comprising an absorbent material positioned within the housing at a downstream end of the analysis channel.

25. The sample analysis cartridge of claim 21, wherein:

the housing comprises a first cover component and a second cover component, which together enclose an internal component and the circuit board;

the internal component is disposed on or under the circuit board;

features of the internal component and the circuit board define the analysis channel; and

features of the internal component define a plurality of reservoirs.

26. The sample analysis cartridge of claim 21, further comprising a sonication component comprising a piezoelectric element, the sonication component aligned with the first reservoir and configured to generate a signal for detection of:

flex in the first reservoir, a change in a return sound wave, or a shift in a resonance frequency of the piezoelectric element upon entry of a sample collection device into the first reservoir.

27. The sample analysis cartridge of claim 21, wherein the signaling agent comprises an oxidizing enzyme for oxidizing the chemical substrate.

28. A kit comprising:

the sample analysis cartridge of claim 21; and

a sample collection device sized to fit at least partially within the input tunnel.

29. The kit of claim 28, wherein the sample collection device is configured to retain a biological sample collected from blood, urine, inside a mouth, or inside a nose.

30. The kit of claim 28, wherein the input tunnel and the sample collection device have complementary locking features configured to securely lock the sample collection device in place within the input tunnel.