Systems and methods for detection and quantification of analytes

• US 10,195,606 B2
• Filed: 12/02/2016
• Issued: 02/05/2019
• Est. Priority Date: 03/11/2013
• Status: Active Grant

• Current Assignee: Cue Health Inc.
• Original Assignee: Cue Health Inc.
• Inventors: Khattak, Ayub, Sever, Clinton
• Primary Examiner(s): White, Dennis
• Application Number:
  US15/368,249
• Publication Number:
  US 20170080421A1
• Time in Patent Office: 795 Days
• 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 configured to be electrically coupled to a sample analysis cartridge, the sample analysis reader comprising:

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;

detect a presence of the sample analysis cartridge electrically coupled to the sample analysis reader;

detect identification information associated with the sample analysis cartridge;

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

detect a sample collection device inserted into the sample analysis cartridge; and

initiate a mixing protocol to mix a sample received from the sample collection device with reagents in fluid in a reservoir in the sample analysis cartridge.

2. The sample analysis reader of claim 1, wherein the processor is configured to initiate the mixing protocol by activating a piezoelectric transducer to mix the sample and the reagents in the fluid in the reservoir.

3. The sample analysis reader of claim 1, wherein the processor is configured to initiate the mixing protocol to facilitate formation of a plurality of sandwich complexes formed of a target analyte from the sample directly or indirectly bound to both a magnetic particle and a signaling agent.

4. The sample analysis reader of claim 1, wherein the processor is configured to initiate the mixing protocol to facilitate hybridization of at least some of the reagents with one or more target analytes from the sample.

5. The sample analysis reader of claim 1, wherein the processor is further configured to receive a signal from the sample analysis cartridge indicative of at least one of a presence, absence, or quantity of one or more target analytes from the sample.

6. The sample analysis reader of claim 5, wherein the processor is further configured to process the received signal and to generate a processed signal comprising information indicative of at least one of a presence, absence, or quantity of one or more target analytes from the sample,

wherein the processor is further configured to cause the processed signal to be transmitted to a mobile device.

7. The sample analysis reader of claim 1, wherein the sample analysis reader is configured to be electrically coupled to a plurality of sample analysis cartridges that are each disposable.

8. The sample analysis reader of claim 1, further comprising a magnetic field generator configured to localize magnetic particles in the mix of the sample and the reagents and the fluid from the reservoir over a sensor at least partially disposed in an analysis channel to form a localized sample over the sensor when the sample analysis cartridge is coupled to the sample analysis reader.

9. The sample analysis reader of claim 8, wherein the processor is further configured to stimulate a first heater such that a first valve within the sample analysis cartridge melts and the mix of the sample and the reagents and the fluid flows out of the reservoir into the analysis channel of the sample analysis cartridge.

10. The sample analysis reader of claim 9, wherein the processor is further configured to stimulate a second heater such that a second valve within the sample analysis cartridge melts and a wash solution flows out of a second reservoir of the sample analysis cartridge into the analysis channel,

wherein the wash solution removes, from the localized sample, the reagents that are not bound to magnetic particles.

11. The sample analysis reader of claim 10, wherein the processor is further configured to stimulate a third heater such that a third valve within the sample analysis cartridge melts and a solution of substrates flows out of a third reservoir of the sample analysis cartridge into the analysis channel,

wherein the reagents comprise signaling agents and the signaling agents within the localized sample react with the substrates to generate a signal detected by the sensor indicative of at least one of a presence, absence, or quantity of one or more target analytes from the sample.

12. The sample analysis reader of claim 1, further comprising a dock to physically couple the sample analysis reader to the sample analysis cartridge.

13. A kit comprising the sample analysis reader of claim 1 and the sample analysis cartridge.

14. The kit of claim 13, further comprising the sample collection device.

15. A non-transitory computer readable medium having instructions stored thereon, wherein the instructions, when executed by a processor of a sample analysis reader, cause the processor to:

detect a presence of a sample analysis cartridge electrically coupled to the sample analysis reader;

detect identification information associated with the sample analysis cartridge;

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

detect a sample collection device inserted into the sample analysis cartridge; and

initiate a mixing protocol to mix a sample received from the sample collection device with reagents in fluid in a reservoir in the sample analysis cartridge.

16. The non-transitory computer readable medium of claim 15, wherein the instructions, when executed by the processor, cause the processor to initiate the mixing protocol by activating a piezoelectric transducer to mix the sample and the reagents in the fluid in the reservoir.

17. The non-transitory computer readable medium of claim 15, wherein the instructions, when executed by the processor, cause the processor to initiate the mixing protocol to facilitate formation of a plurality of sandwich complexes formed of a target analyte from the sample directly or indirectly bound to both a magnetic particle and a signaling agent.

18. The non-transitory computer readable medium of claim 15, wherein the instructions, when executed by the processor, cause the processor to initiate the mixing protocol to facilitate hybridization of at least some of the reagents with one or more target analytes from the sample.

19. The non-transitory computer readable medium of claim 15, wherein the instructions, when executed by the processor, cause the processor to receive a signal from the sample analysis cartridge indicative of at least one of a presence, absence, or quantity of one or more target analytes from the sample.

20. The non-transitory computer readable medium of claim 15, wherein the instructions, when executed by the processor, cause the processor to process the received signal and to generate a processed signal comprising information indicative of at least one of a presence, absence, or quantity of one or more target analytes from the sample, and

wherein the instructions cause the processed signal to be transmitted to a mobile device.

21. The non-transitory computer readable medium of claim 15, wherein the instructions, when executed by the processor, cause the processor to stimulate a first heater such that a first valve within the sample analysis cartridge melts and the mix of the sample and the reagents and the fluid flows out of the reservoir into an analysis channel to form a localized sample over a sensor at least partially disposed within the analysis channel of the sample analysis cartridge.

22. The non-transitory computer readable medium of claim 21, wherein the instructions, when executed by the processor, cause the processor to stimulate a second heater such that a second valve within the sample analysis cartridge melts and a wash solution flows out of a second reservoir of the sample analysis cartridge into the analysis channel, and

wherein the wash solution removes, from the localized sample, the reagents that are not bound to magnetic particles.

23. The non-transitory computer readable medium of claim 22, wherein the instructions, when executed by the processor, cause the processor to stimulate a third heater such that a third valve within the sample analysis cartridge melts and a solution of substrates flows out of a third reservoir of the sample analysis cartridge into the analysis channel,

wherein the reagents comprise signaling agents and the signaling agents within the localized sample react with the substrates to generate a signal detected by the sensor indicative of at least one of a presence, absence, or quantity of one or more target analytes from the sample.