Systems and methods for detection and quantification of analytes

• US 9,034,168 B2
• Filed: 09/05/2014
• Issued: 05/19/2015
• 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): NOGUEROLA, ALEXANDER STEPHAN
• Application Number:
  US14/479,149
• Publication Number:
  US 20150064693A1
• Time in Patent Office: 256 Days
• US Class Current: 205/775.5
• 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 reader for detecting the presence, absence, and/or a quantity of a target analyte, comprising:

a dock for physically coupling the sample analysis reader to a cartridge, the cartridge comprising a housing with analyte detection reagents and an electrochemical sensor stored therein;

a magnetic field generator configured to localize a magnetic particle if present when the cartridge is coupled to the sample analysis reader;

a circuit having a cartridge detection unit comprising electrical pins for electrically coupling the sample analysis reader to the cartridge;

a processor; and

a non-transitory computer-readable medium having instructions stored thereon, wherein the instructions, when executed by the processor, cause the processor to process electrical signals received from the electrochemical sensor of the cartridge via the circuit.

2. The sample analysis reader of claim 1, wherein the electrical signals correspond to an oxidation-reduction reaction occurring at the electrochemical sensor, the electrical signals and the oxidation-reduction reaction indicative of the presence, absence, and/or quantity of a target analyte.

3. The sample analysis reader of claim 1, wherein the dock is configured to align the sample analysis reader with the cartridge such that, when coupled, the electrochemical sensor in the cartridge is electrically coupled to the circuit of the sample analysis reader and positioned within a magnetic field created by the magnetic field generator.

4. The sample analysis reader of claim 1, wherein the dock is configured to interchangeably couple to a plurality of cartridges.

5. The sample analysis reader of claim 1, wherein the dock comprises a slot, opening, bed, port, or other docking feature disposed within or on a reader housing.

6. The sample analysis reader of claim 1, wherein the magnet field generator comprises a plurality of magnet field generators, and wherein, when the sample analysis reader is coupled to the cartridge, the plurality of magnet field generators are aligned with a plurality of electrochemical sensors spaced along an axis lying on a plane of the cartridge, each magnet field generator configured to exert a different magnetic field strength on the plane of the cartridge.

7. The sample analysis reader of claim 6, wherein the plurality of magnetic field generators comprises a plurality of permanent magnets.

8. The sample analysis reader of claim 6, wherein the plurality of magnetic field generators comprises a plurality of electromagnets.

9. The sample analysis reader of claim 1, further comprising a sonication component electrically coupled to the circuit, wherein when the sample analysis reader is coupled to the cartridge, the sonication component is aligned with a sample preparation reservoir in the cartridge.

10. The sample analysis reader of claim 9, wherein the sonication component comprises a piezoelectric component electrically coupled to the processor, the piezoelectric component positioned such that the processor is configured to receive signals from the piezoelectric component and detect:

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

11. The sample analysis reader of claim 1, wherein the instructions, when executed by the processor, further cause the processor to:

identify a proper test protocol for the cartridge coupled to the dock based at least in part on cartridge identification information received from the circuit;

stimulate a piezoelectric component to generate a test signal within a sample preparation reservoir of the cartridge, the piezoelectric component coupled to the circuit, aligned with the sample preparation reservoir, and forming a component of the cartridge or the sample analysis reader;

receive a return signal or a resonance signal from the piezoelectric component;

detect entry of a sample collection device into the sample preparation reservoir based at least in part on a change in the return signal or a shift in the resonance signal; and

initiate a sonication protocol for the piezoelectric component to mix reagents and analytes within a liquid disposed within the sample preparation reservoir, wherein mixing facilitates hybridization of at least some of the reagents with the analytes.

12. The sample analysis reader of claim 1, wherein the instructions, when executed by the processor, further cause the processor to transmit data, based at least in part on the electrical signals, to a mobile computing device or display device.

13. The sample analysis reader of claim 1, wherein the instructions, when executed by the processor, further cause the processor to transmit a signal to the circuit to deliver an electric current sequentially to a plurality of heating elements.

14. The sample analysis reader of claim 1, wherein the sample analysis reader is less than 30 cm in height, less than 30 cm in width, and less than 30 cm in length.

15. A molecule detection system, comprising:

the sample analysis reader of claim 1; and

the cartridge.

16. The molecule detection system of claim 15, wherein the cartridge comprises:

a cartridge housing having internal barriers defining a plurality of reservoirs, an analysis channel, and an input tunnel, and

a circuit board coupled to form a wall of the analysis channel and comprising the electrochemical sensor, wherein the electrochemical sensor is disposed within a portion of the analysis channel.

17. The molecule detection system of claim 16, further comprising a sample collection device sized to fit at least partially within the input tunnel.

18. The molecule detection system of claim 15, further comprising a sonication component electrically coupled to the circuit and aligned with a first of the plurality of reservoirs, the sonication component forming a component of the cartridge or the sample analysis reader.

19. The molecule detection system of claim 15, wherein the cartridge is configured to removably couple to the dock of the sample analysis reader.

20. A method for preparing a sample for target analyte detection, the method performed by the sample analysis reader of claim 1, the method comprising:

detecting the presence of a cartridge loaded into or onto the sample analysis reader and detecting identification information associated with the cartridge;

identifying a proper test protocol for the cartridge based at least in part on the identification information;

detecting a sample collection device inserted into a first reservoir of the cartridge; and

initiating a mixing protocol to mix a plurality of reagents, a plurality of magnetic particles, a plurality of detector agents or competitive binding agents, and a plurality of analytes from the sample within the first reservoir, wherein;

if detector agents are provided, a resulting mixture comprises;

a plurality of sandwich complexes formed of a target analyte bound to both a surface affinity molecule on a magnetic particle surface and a detector agent, and

if competitive binding agents are provided, the resulting mixture comprises;

a first plurality of molecule complexes each formed of a competitive binding agent bound to a surface affinity molecule on a magnetic particle surface, and a second plurality of molecule complexes each formed of a target analyte bound to a surface affinity molecule on a magnetic particle surface.

21. The method of claim 20, wherein the mixing protocol is performed by a sonication component.

22. The method of claim 20, further comprising:

stimulating a first heating element such that a first valve within the cartridge melts and the resulting mixture flows out of the first reservoir into an analysis channel of the cartridge, wherein the magnetic particles within the resulting mixture localize over a magnetic field within a portion of the analysis channel, forming a localized sample;

stimulating a second heating element such that a second valve within the cartridge melts and a wash solution flows out of a second reservoir of the cartridge into the analysis channel, wherein the wash solution removes, from the localized sample, detector agents or competitive binding agents that are not bound to magnetic particles;

stimulating a third heating element such that a third valve within the cartridge melts and a solution of substrates flows out of a third reservoir of the cartridge into the analysis channel,

wherein detector agents or competitive binding agents within the localized sample comprise oxidizing enzymes that oxidize the substrates, causing electrons to flow from the electrochemical sensor of the cartridge at the site of the localized sample.

23. The method of claim 22, wherein the resulting mixture, the wash solution, and the solution of substrates flow via capillary action.

24. The method of claim 22, wherein:

if detector agents are present, electrons flow in a quantity proportional to a quantity of target analyte present within the localized sample, and

if competitive binding agents are present, electrons flow in a quantity inversely proportional to a quantity of target analyte present within the localized sample.

25. A method of detecting the presence, absence, and/or quantity of a target analyte within a sample, the method comprising:

performing the method of claim 24;

detecting a first signal at a recording electrochemical sensor located in the cartridge in or near the analysis channel, wherein at least a portion of the first signal results from the oxidation of the substrate;

detecting a second signal at a reference electrochemical sensor located in the cartridge;

removing the second signal from the first signal to generate a resultant signal; and

processing and analyzing the resultant signal to identify a test result, the test result indicating the presence, absence, and/or quantity of the target analyte.

26. The method of claim 25, further comprising transmitting signals indicative of the test result to a mobile computing device.