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

• US 9,623,409 B2
• Filed: 10/27/2016
• Issued: 04/18/2017
• 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, Nelson, Paul, Cooper, Ryan, Congdon, Thomas, Demartino, Justin, Shapiro, Raphael, Duncan, Mark
• Primary Examiner(s): WHITE, DENNIS MICHAEL
• Application Number:
  US15/336,735
• Publication Number:
  US 20170043336A1
• Time in Patent Office: 173 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;

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

a piezoelectric transducer that forms at least part of a wall of the reservoir, the piezoelectric transducer configured to emit energy into the reservoir to mix the fluid, the sample, and reagents; and

a shuttle defining a first compartment and a second compartment, the first and second compartment configured to be disposed within the reservoir in a mixing position, wherein the piezoelectric transducer is configured to emit the 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.

2. The sample analysis cartridge of claim 1, 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.

3. The sample analysis cartridge of claim 1, wherein the shuttle comprises a compartment divider configured to divide the first compartment from the second compartment.

4. The sample analysis cartridge of claim 3, wherein the energy emission and the fluid flowing around the compartment divider facilitates formation of a wave pattern.

5. The sample analysis cartridge of claim 3, wherein the compartment divider comprises a slot configured to permit the fluid, the sample, and the reagents to flow through the compartment divider via the slot during mixing.

6. The sample analysis cartridge of claim 3, wherein the compartment divider is a flange.

7. The sample analysis cartridge of claim 1, wherein the first compartment comprises a reagent ball compartment configured to house a reagent ball comprising the reagents and the second compartment comprises a sample compartment configured to receive the sample from the sample collection device.

8. The sample analysis cartridge of claim 7, wherein the reagent ball comprises polymerases, primers, and signaling agents.

9. The sample analysis cartridge of claim 1, wherein the piezoelectric transducer comprises a piezoceramic disc.

10. The sample analysis cartridge of claim 1, wherein the piezoelectric transducer is adhered to the reservoir to form at least the part of the wall 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.

11. The sample analysis cartridge of claim 1, wherein the piezoelectric transducer forms a portion of a bottom surface of the reservoir.

12. The sample analysis cartridge of claim 1, wherein the reservoir is substantially symmetric.

13. The sample analysis cartridge of claim 1, 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.

14. The sample analysis cartridge of claim 1, wherein the piezoelectric transducer is positioned off-center of a longitudinal axis of the reservoir to facilitate mixing of the fluid, the sample, and the reagents within the reservoir.

15. The sample analysis cartridge of claim 1, further comprising a printed circuit board coupled to the piezoelectric transducer via one or more spring contacts.

16. The sample analysis cartridge of claim 15, wherein the piezoelectric transducer is electrically coupled to the printed circuit board only via the one or more spring contacts.

17. The sample analysis cartridge of claim 1, wherein the piezoelectric transducer is activated responsive to a signal from a processor.

18. 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.

19. The sample analysis cartridge of claim 18, wherein the temperature sensor is disposed on a printed circuit board positioned adjacent the piezoelectric transducer.

20. The sample analysis cartridge of claim 18, wherein the piezoelectric transducer is configured to emit the energy in a modified manner based on the sensed temperature.

21. 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,

wherein the piezoelectric transducer is configured to emit the energy after actuation of the contact switch.

22. The sample analysis cartridge of claim 1, wherein the sample comprises one or more nucleic acids, and

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

23. The sample analysis cartridge of claim 22, wherein the energy emitted by the piezoelectric transducer is configured to cause an amplification reaction to cure on the one or more nucleic acids.

24. The sample analysis cartridge of claim 1, further comprising a sensor positioned to be exposed to the fluid mixed with the reagents and the sample, the 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.

25. The sample analysis cartridge of claim 24, wherein the reagents comprise a plurality of affinity molecules and a plurality of signaling agents.

26. The sample analysis cartridge of claim 24, wherein the reagents comprise a plurality of magnetic particles configured to be magnetically held over a target working electrode of the sensor.

27. The sample analysis cartridge of claim 24, further comprising an analysis channel, wherein at least a portion of the sensor is disposed in the analysis channel and the fluid mixed with the reagents and the sample travels to at least the portion of the sensor via the analysis channel.

28. The sample analysis cartridge of claim 27, further comprising a substrate reservoir configured to hold a substrate solution comprising a 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 of the reagents localized over the sensor to generate the signal.

29. The sample analysis cartridge of claim 1, wherein the piezoelectric transducer is configured to emit the energy into the reservoir to move the fluid in the reservoir in a wave pattern between the first and second compartments.