Cartridges, kits, and methods for enhanced detection and quantification of analytes

• US 9,718,058 B2
• Filed: 10/27/2016
• Issued: 08/01/2017
• Est. Priority Date: 07/17/2015
• Status: Active Grant

• Current Assignee: Cue Health Inc.
• Original Assignee: Cue, Inc. (Cue Health Inc.)
• Inventors: Nelson, Paul, Khattak, Ayub, Sever, Clinton, Cooper, Ryan, Congdon, Thomas, Demartino, Justin, Shapiro, Raphael, Duncan, Mark
• Primary Examiner(s): Turk, Neil N
• Application Number:
  US15/336,487
• Publication Number:
  US 20170045507A1
• Time in Patent Office: 278 Days
• Field of Search: None
• CPC Class Codes: A61B 10/0045 Devices for taking samples of body liquids devices for taking blood samples A61B5/15
• CPC Class Codes: A61B 10/02 Instruments for taking cell samples or for biopsy A61B10/0038 and A61B10/0045 take precedence; needle locating or guiding means A61B17/3403; samplers for enzymology or microbiology C12M1/26; sampling or preparing biological specimens G01N33/48
• CPC Class Codes: A61B 5/157 Devices characterised by integrated means for measuring characteristics of blood
• CPC Class Codes: B01L 2200/025 Align devices or objects to ensure defined positions relative to each other
• CPC Class Codes: B01L 2200/027 for microfluidic devices
• 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 2200/10 Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
• CPC Class Codes: B01L 2200/14 Process control and prevention of errors
• 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 2300/044 pierceable, e.g. films, membranes
• CPC Class Codes: B01L 2300/047 Additional chamber, reservoir
• 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 2300/0663 Whole sensors
• CPC Class Codes: B01L 2300/0672 Integrated piercing tool
• CPC Class Codes: B01L 2300/069 Absorbents; Gels to retain a fluid
• CPC Class Codes: B01L 2300/0809 rectangular shaped
• CPC Class Codes: B01L 2300/0816 : Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• 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 2300/1805 : Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks
• CPC Class Codes: B01L 2300/1827 : using resistive heater
• CPC Class Codes: B01L 2400/0406 : capillary forces
• CPC Class Codes: B01L 2400/0481 : squeezing of channels or chambers
• CPC Class Codes: B01L 2400/0677 : phase change valves; Meltable, freezing, dissolvable plugs; Destructible barriers
• CPC Class Codes: B01L 3/5023 : with a sample being transported to, and subsequently stored in an absorbent for analysis
• 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 3/502738 : 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 3/523 : with means for closing or opening
• CPC Class Codes: B01L 3/527 : for a plurality of reagents
• CPC Class Codes: B65D 83/005 : the piston or movable bottom being pulled upwards to dispense the contents
• CPC Class Codes: B65D 83/04 : for dispensing annular, disc-shaped, or spherical or like small articles, e.g. tablets or pills
• CPC Class Codes: B65D 83/0817 : the articles being automatically urged towards the dispensing aperture, e.g. spring-loaded B65D83/0823 takes precedence
• CPC Class Codes: B65D 83/0858 : the articles being automatically urged towards the dispensing aperture, e.g. spring-loaded B65D83/0864 takes precedence
• CPC Class Codes: C12Q 1/6825 : Nucleic acid detection involving sensors
• 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 33/54366 : Apparatus specially adapted for solid-phase testing
• 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 35/10 : Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices G01N35/0099 takes precedence

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 for detecting at least one of a presence, absence, or quantity of one or more analytes, the sample analysis cartridge comprising:

a housing;

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

a reservoir configured to hold a fluid, the reservoir disposed within the housing adjacent to the input tunnel and configured to receive the sample from the sample collection device;

a shuttle disposed in the input tunnel between the reservoir and the aperture in a first position, the shuttle comprising a body having a first end and a second end and a compartment therebetween, the shuttle configured to house a reagent ball comprising reagents within the compartment, the shuttle configured to seal the reservoir from the input tunnel at the first end in the first position, the shuttle comprising an opening at the second end configured to receive the sample collected by the sample collection device, the shuttle configured to move within the input tunnel when subjected to a force greater than a threshold force to a second position such that the reagent ball and the sample move into the reservoir and the reservoir maintains the fluid therein during movement from the first position to the second position; and

a sensor positioned within the housing to be exposed to the fluid mixed with the reagent ball and the sample from the reservoir, the sensor configured to generate a signal indicative of at least one of the presence, absence, or quantity of the one or more analytes within the sample.

2. The sample analysis cartridge of claim 1, wherein the shuttle is configured to wipe excess sample from a tip of the sample collection device inserted in the opening at the second end so that, at most, a predetermined volume of the sample is mixed in the fluid within the reservoir.

3. The sample analysis cartridge of claim 1, wherein the shuttle is configured to receive the sample compressed from the sample collection device in the input tunnel through the opening at the second end.

4. The sample analysis cartridge of claim 1, wherein the shuttle comprises a first sealing member at the first end to facilitate sealing the reservoir from the input tunnel in the first position, and

wherein the reservoir is sealed during movement from the first position to the second position via the sample collection device partially inserted within the opening at the second end of the shuttle and a second sealing member at the second end.

5. The sample analysis cartridge of claim 1, further comprising one or more locking members disposed within the input tunnel and configured to irreversibly lock the sample collection device within the input tunnel in the second position.

6. The sample analysis cartridge of claim 1, wherein the compartment is a reagent ball compartment and the shuttle further comprises a sample compartment configured to house, at most, a predetermined volume of the sample,

wherein the sample compartment and the reagent ball compartment are positioned in the input tunnel to not be exposed to the fluid within the reservoir in the first position, and

wherein the movement of the shuttle causes the sample compartment and the reagent ball compartment to be exposed to the fluid within the reservoir in the second position.

7. The sample analysis cartridge of claim 6, wherein the shuttle comprises a compartment divider that divides the sample compartment from the reagent ball compartment.

8. The sample analysis cartridge of claim 7, wherein the compartment divider comprises a slot configured to promote mixing when disposed within the reservoir in the second position.

9. The sample analysis cartridge of claim 1, wherein the reagent ball comprising the reagents comprises one or more of a plurality of solid particles, a plurality of affinity molecules, or a plurality of signaling agents.

10. The sample analysis cartridge of claim 1, wherein the sensor comprises a working electrode and the reagent ball comprising the reagents comprises a plurality of magnetic particles configured to be magnetically held over the working electrode of the sensor.

11. The sample analysis cartridge of claim 10, wherein the working electrode is masked with a plurality of striations configured to promote homogenous distribution of the plurality of magnetic particles localized over the working electrode and to promote resistance to movement of the plurality of magnetic particles off of the working electrode.

12. The sample analysis cartridge of claim 10, wherein at least one magnetic particle of the plurality of magnetic particles is configured to be indirectly bound to a signaling agent.

13. The sample analysis cartridge of claim 1, wherein the sensor comprises a target working electrode, further comprising a positive control working electrode comprising affinity molecules pre-bound to the positive control working electrode, the positive control working electrode configured to generate a control signal based on a reaction between signaling agents directly or indirectly bound to the affinity molecules and a substrate,

wherein the target working electrode is configured to generate the signal indicative of at least one of the presence, absence, or quantity of the one or more analytes within the sample, and

wherein a test is determined to be reliable if the control signal indicates a quantity of the reaction within a predetermined range.

14. The sample analysis cartridge of claim 1, further comprising an analysis channel disposed within the housing, wherein at least a portion of the sensor is disposed in the analysis channel and the fluid mixed with the reagent ball and the sample travels to at least the portion of the sensor via the analysis channel.

15. The sample analysis cartridge of claim 14, further comprising a substrate reservoir disposed within the housing and configured to hold a substrate solution, 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.

16. The sample analysis cartridge of claim 15, further comprising a wash reservoir disposed within the housing and configured to hold a wash solution, the wash reservoir comprising an outlet configured to permit the wash solution to travel therethrough and into the analysis channel to at least the portion of the sensor.

17. The sample analysis cartridge of claim 1, further comprising a sealing material and a seal piercer, the sealing material configured to fluidicly seal the fluid within the reservoir and the seal piercer configured to pierce the sealing material during insertion of the sample collection device into the input tunnel.

18. The sample analysis cartridge of claim 1, further comprising a contact switch positioned in the input tunnel to be activated during insertion of the sample collection device in the input tunnel.

19. The sample analysis cartridge of claim 1, wherein the one or more analytes within the sample comprise one or more nucleic acids, and

wherein the reservoir is configured to permit amplification of the one or more nucleic acids within the sample.

20. The sample analysis cartridge of claim 1, further comprising a piezoelectric transducer disposed within the housing and configured to emit energy into the reservoir to mix the fluid, the reagent ball, and the sample.

21. The sample analysis cartridge of claim 20, wherein the piezoelectric transducer forms at least part of a wall of the reservoir.

22. The sample analysis cartridge of claim 21, further comprising a temperature sensor configured to sense temperature indicative of temperature of the fluid in the reservoir,

wherein the piezoelectric transducer is configured to emit energy in a modified manner based on the sensed temperature.

23. The sample analysis cartridge of claim 1, further comprising one or more heaters disposed within the housing,

wherein the reservoir comprises an outlet having a phase-changeable material therein to occlude an entire cross-section of the outlet, and

wherein at least one of the one or more heaters is configured to heat the phase-changeable material such that the phase-changeable material does not occlude the entire cross-section of the outlet.

24. The sample analysis cartridge of claim 23, further comprising a fluidic isolator comprising phase-changeable material,

wherein at least one of the one or more heaters is configured to heat phase-changeable material of the fluidic isolator after unsealing the reservoir outlet such that phase-changeable material of the fluidic isolator flows into an analysis channel to fluidicly isolate the reservoir from a substrate reservoir.

25. The sample analysis cartridge of claim 1, further comprising a collet disposed in the input tunnel and coupled to the shuttle in the first position, the collet configured to decouple from the shuttle during insertion of the sample collection device in the input tunnel,

wherein the shuttle is configured to move within the input tunnel from the first position to the second position while the collet remains in place in the input tunnel.

26. The sample analysis cartridge of claim 1, wherein the sample analysis cartridge is sized to be at least partially disposed within, and electrically coupled to, a reader configured to receive and process the signal indicative of at least one of the presence, absence, or quantity of the one or more analytes within the sample.

27. The sample analysis cartridge of claim 1, wherein the reservoir is substantially symmetric and is formed of walls, wherein each of the walls of the reservoir meet at an angle greater than 60°

to facilitate fluid emptying through an outlet of the reservoir.