Systems and methods for detection and quantification of analytes

• US 9,086,417 B2
• Filed: 01/16/2015
• Issued: 07/21/2015
• 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): Sines, Brian J
• Application Number:
  US14/599,365
• Publication Number:
  US 20150133337A1
• Time in Patent Office: 186 Days
• Field of Search: 436/43, 436/63, 436/149, 422/502, 422/554, 422/68.1, 422/82.01
• US Class Current: 1/1
• 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 method for identifying a presence and/or quantity of a target analyte within a sample in a cartridge, the method comprising:

initiating a mixing protocol to form a mixture within a reservoir of the cartridge, wherein the mixture comprises a plurality of magnetic particles each bound directly or indirectly to a respective one of a plurality of agents comprising oxidizing enzymes and/or the target analyte present in the sample;

facilitating movement of the mixture from the reservoir into an analysis channel of the cartridge, wherein the magnetic particles and the agents and/or the target analyte bound thereto localize on a portion of the analysis channel within a magnetic field, forming a localized sample;

facilitating movement of a plurality of substrates into the analysis channel, wherein the oxidizing enzymes of the agents within the localized sample oxidize the substrates;

receiving a signal from an electrochemical sensor, wherein at least a portion of the signal results from the oxidation of the substrates; and

analyzing the signal to identify the presence and/or quantity of the target analyte in the sample.

2. The method of claim 1, wherein the method is performed by an analyte reader coupled to the cartridge.

3. The method of claim 2, further comprising detecting identification information associated with the cartridge coupled to the analyte reader;

and identifying a protocol appropriate for the cartridge based at least in part on the identification information.

4. The method of claim 2, wherein the sample is introduced into the reservoir by insertion of a sample collection device into the reservoir of the cartridge, and wherein the method further comprises detecting insertion of the sample collection device into the reservoir.

5. The method of claim 4, wherein the mixing protocol is initiated upon detecting the insertion of the sample collection device.

6. The method of claim 1, wherein initiating the mixing protocol comprises stimulating a piezoelectric component in or near the reservoir.

7. The method of claim 1, wherein the agents comprise at least one of detector agents and competitive binding agents, wherein said competitive binding agents each comprise a target analyte and a signaling agent.

8. The method of claim 7, wherein:

if the detector agents are provided, the mixture more specifically comprises;

a plurality of sandwich complexes each formed of the target analyte bound both to an affinity molecule on a surface of one of the magnetic particles and to one of the detector agents, and/or

if the competitive binding agents are provided, the mixture more specifically comprises;

a plurality of molecule complexes each formed of one of the competitive binding agents bound to a affinity molecule on a surface of one of the magnetic particles.

9. The method of claim 1, wherein facilitating movement of the mixture from the reservoir comprises stimulating a heating element thermally coupled to a valve in an outlet of the reservoir such that the valve undergoes a phase change and the mixture flows from the reservoir into the analysis channel.

10. The method of claim 1, wherein facilitating movement of the plurality of substrates comprises stimulating a heating element thermally coupled to a valve in an outlet of a substrate-holding reservoir within the cartridge such that the valve undergoes a phase change and the substrates flows from the substrate-holding reservoir into the analysis channel.

11. The method of claim 1, further comprising stimulating a heating element thermally coupled to a valve in an outlet of a wash-holding reservoir within the cartridge such that the valve undergoes a phase change and a wash solution flows from the wash-holding reservoir into the analysis channel, wherein the wash solution removes, from the localized sample, agents unbound to magnetic particles.

12. The method of claim 7, wherein:

if the detector agents are present, a quantity of electrons released from the electrochemical sensor is proportional to a quantity of target analyte present within the localized sample, and/or

if the competitive binding agents are present, a quantity of electrons released from the electrochemical sensor is inversely proportional to a quantity of target analyte present within the localized sample.

13. The method of claim 1, wherein analyzing the signal received from the electrochemical sensor comprises detecting a first signal at a recording electrode of the electrochemical sensor;

detecting a second signal comprising noise at a reference electrode of the electrochemical sensor; and

calculating a resultant signal by applying an algorithm to remove the second signal from the first signal.

14. The method of claim 1, further comprising transmitting signals to a mobile computing device, wherein the signals identify the presence and/or quantity of the target analyte in the sample.

15. The method of claim 1, wherein the magnetic particles comprise at least one or both of:

a plurality of larger magnetic particles each having a first affinity molecule on its surface configured to bind to a first target analyte, or a plurality of smaller magnetic particles each having a second affinity molecule on its surface configured to bind to a second target analyte.

16. The method of claim 15, wherein localizing on the portion of the analysis channel comprises localizing over a plurality of magnetic fields within the portion of the analysis channel, thereby forming a plurality of localized samples, wherein the magnetic particles localize over the magnetic fields based on size and strength such that the larger magnetic particles localize over a smaller upstream magnetic field and a first electrochemical sensor, and the smaller magnetic particles localize over a larger downstream magnetic field and a second electrochemical sensor.

17. The method of claim 16, wherein analyzing the signal comprises processing and analyzing a signal from the first electrochemical sensor to identify a presence and/or quantity of the first target analyte;

and processing and analyzing a signal from the second electrochemical sensor to identify a presence and/or quantity of the second target analyte.

18. The method of claim 11, wherein an absorbent material at a downstream-most end of the analysis channel absorbs waste liquids.

19. The method of claim 1, wherein the magnetic field is generated by at least one of a permanent magnet and an electromagnet.

20. The method of claim 19, wherein the magnetic field comprises a plurality of magnetic fields generated by magnets of varying size or varying distance from the analysis channel.