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

• US 9,724,691 B2
• Filed: 10/27/2016
• Issued: 08/08/2017
• Est. Priority Date: 07/17/2015
• Status: Active Grant

• Current Assignee: Cue Health Inc.
• Original Assignee: Cue, Inc. (Cue Health Inc.)
• Inventors: Nelson, Paul, Cooper, Ryan, Congdon, Thomas, Demartino, Justin, Shapiro, Raphael, Duncan, Mark, Khattak, Ayub, Sever, Clinton
• Primary Examiner(s): HIXSON, CHRISTOPHER
• Application Number:
  US15/336,715
• Publication Number:
  US 20170043342A1
• Time in Patent Office: 285 Days
• 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 microfluidic cartridge comprising:

a reservoir configured to hold a fluid, the reservoir further configured to receive a sample from a sample collection device, the reservoir comprising an outlet having a phase-changeable material therein to occlude an entire cross-section of the outlet; and

a circuit board comprising;

a sensor configured to generate a signal indicative of at least one of a presence, absence, or quantity of one or more analytes within the sample;

circuitry configured to be activated by insertion of the sample collection device;

a temperature sensor positioned on the circuit board to sense temperature indicative of temperature of the fluid in the reservoir; and

one or more heaters, 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.

2. The microfluidic cartridge of claim 1, wherein the circuit board further comprises one or more spring contacts coupled to a piezoelectric transducer.

3. The microfluidic cartridge of claim 2, wherein the piezoelectric transducer is configured to emit energy into the reservoir to mix the fluid, the sample, and reagents.

4. The microfluidic cartridge of claim 3, wherein the piezoelectric transducer forms at least a part of a wall of the reservoir.

6. The microfluidic cartridge of claim 3, wherein the piezoelectric transducer is configured to emit energy in a modified manner based on the sensed temperature.

7. The microfluidic cartridge of claim 1, wherein the circuit board forms a wall of an analysis channel such that the sensor is positioned in the analysis channel, and

wherein the analysis channel is configured to receive the fluid and the sample from the reservoir.

8. The microfluidic 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.

9. The microfluidic cartridge of claim 8, further comprising a negative control working electrode comprising a self-assembled monolayer, the negative control working electrode configured to generate a negative control signal based on a reaction between the substrate and any signaling agents localized at the negative working electrode.

10. The microfluidic cartridge of claim 9, wherein the negative control signal is indicative of reliability of the test.

11. The microfluidic cartridge of claim 1, wherein the circuitry comprises a contact switch configured to send a signal indicative of insertion of the sample collection device within the microfluidic cartridge.

12. The microfluidic cartridge of claim 9, wherein the sensor further comprises a reference electrode and a counter electrode.

13. The microfluidic cartridge of claim 8, wherein the target working electrode is masked with a plurality of striations configured to promote homogenous distribution of a plurality of magnetic particles localized over the target working electrode and to promote resistance to movement of the plurality of magnetic particles off of the target working electrode.

14. The microfluidic cartridge of claim 8, wherein the target working electrode comprises affinity molecules pre-bound to the working electrode.

15. The microfluidic 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.

16. The microfluidic cartridge of claim 1, wherein the circuit board further comprises 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.

17. The microfluidic cartridge of claim 1, wherein at least one of the one or more heaters is configured to be heated by a resistor in the circuit board that is not electrically coupled to the at least one heater.

18. The microfluidic cartridge of claim 1, wherein the microfluidic cartridge is sized to be at least partially disposed within, and electrically coupled via a plurality of leads on the circuit board 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.

5. A microfluidic cartridge comprising:

a reservoir configured to hold a fluid, the reservoir further configured to receive a sample from a sample collection device;

a piezoelectric transducer configured to emit energy into the reservoir to mix the fluid, the sample, and reagents, wherein the piezoelectric transducer is adhered to the reservoir to form at least a part of a wall of the reservoir using an annulus of adhesive applied on a top surface of the piezoelectric transducer to permit fluidic sealing between the piezoelectric transducer and the reservoir while permitting the piezoelectric transducer to vibrate; and

a circuit board comprising;

one or more spring contacts coupled to the piezoelectric transducer;

a sensor configured to generate a signal indicative of at least one of a presence, absence, or quantity of one or more analytes within the sample;

circuitry configured to be activated by insertion of the sample collection device; and

a temperature sensor positioned on the circuit board to sense temperature indicative of temperature of the fluid in the reservoir.

19. A circuit board for a microfluidic cartridge configured to receive a sample from a sample collection device, the circuit board comprising:

a sensor configured to generate a signal indicative of at least one of a presence, absence, or quantity of one or more analytes within the sample;

circuitry configured to be activated by insertion of the sample collection device;

a temperature sensor positioned on the circuit board to sense temperature indicative of temperature of fluid in a reservoir; and

one or more heaters configured to heat phase-changeable material to open one or more valves.

20. The circuit board of claim 19, wherein the circuit board comprises one or more spring contacts coupled to a piezoelectric transducer.

21. The circuit board of claim 19, wherein the circuit board forms a wall of an analysis channel such that the sensor is positioned in the analysis channel.

22. The circuit board of claim 19, 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.

23. The circuit board of claim 22, further comprising a negative control working electrode comprising a self-assembled monolayer, the negative control working electrode configured to generate a negative control signal based on a reaction between the substrate and any signaling agents localized at the negative working electrode, and

wherein the negative control signal is indicative of reliability of the test.

24. The circuit board of claim 19, wherein the circuitry comprises a contact switch configured to send a signal indicative of insertion of the sample collection device within the microfluidic cartridge.

26. The circuit board of claim 22, wherein the target working electrode comprises a self-assembled monolayer or affinity molecules pre-bound to the target working electrode or both.

27. The circuit board of claim 19, 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 an outlet of a sample preparation reservoir such that phase-changeable material of the fluidic isolator flows into an analysis channel to fluidicly isolate the sample preparation reservoir from a substrate reservoir.

28. The circuit board of claim 19, wherein at least one of the one or more heaters is configured to be heated by a resistor in the circuit board that is not electrically coupled to the at least one heater.

25. A circuit board for a microfluidic cartridge configured to receive a sample from a sample collection device, the circuit board comprising:

a sensor configured to generate a signal indicative of at least one of a presence, absence, or quantity of one or more analytes within the sample, the sensor comprising a target working electrode masked with a plurality of striations configured to promote homogenous distribution of a plurality of magnetic particles localized over the target working electrode and to promote resistance to movement of the plurality of magnetic particles off of the target working electrode.

29. The circuit board of claim 25, 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.

30. The circuit board of claim 25, further comprising a negative control working electrode comprising a self-assembled monolayer, the negative control working electrode configured to generate a negative control signal based on a reaction between the substrate and any signaling agents localized at the negative working electrode, and

wherein the negative control signal is indicative of reliability of the test.