Devices and methods for molecular diagnostic testing

• US 10,525,469 B2
• Filed: 04/05/2019
• Issued: 01/07/2020
• Est. Priority Date: 12/31/2014
• Status: Active Grant

• Current Assignee: Visby Medical, Inc.
• Original Assignee: Visby Medical, Inc.
• Inventors: Andreyev, Boris, Moravick, Keith E., Ciopyk, Brian, Briones, Victor, Loney, Gregory, De La Zerda, Adam, Ching, Jesus, Chu, Steven, Swenson, David, Huang, Helen, Kelly, Colin
• Primary Examiner(s): Hurst, Jonathan M
• Application Number:
  US16/376,383
• Publication Number:
  US 20190232283A1
• Time in Patent Office: 277 Days
• CPC Class Codes: B01L 2200/025 Align devices or objects to ensure defined positions relative to each other
• CPC Class Codes: B01L 2200/028 Modular arrangements
• CPC Class Codes: B01L 2200/0647 Handling flowable solids, e.g. microscopic beads, cells, particles
• 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 2300/0627 Sensor or part of a sensor is integrated
• CPC Class Codes: B01L 2300/0654 Lenses; Optical fibres
• CPC Class Codes: B01L 2300/0672 Integrated piercing tool
• CPC Class Codes: B01L 2300/0681 Filter
• CPC Class Codes: B01L 2300/0867 Multiple inlets and one sample wells, e.g. mixing, dilution
• CPC Class Codes: B01L 2300/0883 Serpentine channels
• CPC Class Codes: B01L 2300/18 Means for temperature control
• CPC Class Codes: B01L 2300/1822 using Peltier elements
• CPC Class Codes: B01L 2300/1844 using fans
• CPC Class Codes: B01L 2400/0457 passive flow or gravitation
• CPC Class Codes: B01L 2400/0478 pistons
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 2400/0605 check valves
• CPC Class Codes: B01L 2400/0611 duck bill valves
• CPC Class Codes: B01L 2400/0644 : rotary valves
• 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 3/5029 : using swabs
• CPC Class Codes: B01L 3/527 : for a plurality of reagents
• 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: B01L 7/525 : with physical movement of samples between temperature zones

Abstract

A hand-held molecular diagnostic test device includes a housing, an amplification (or PCR) module, and a detection module. The amplification module is configured to receive an input sample, and defines a reaction volume. The amplification module includes a heater such that the amplification module can perform a polymerase chain reaction (PCR) on the input sample. The detection module is configured to receive an output from the amplification module and a reagent formulated to produce a signal that indicates a presence of a target amplicon within the input sample. The amplification module and the detection module are integrated within the housing.

Claims

1. An apparatus, comprising:

a housing;

a sample input module enclosed by the housing, the sample input module defining a sample input volume that receives an input sample;

a solid positive control within the sample input module, the solid positive control being nonpathogenic to humans and being rehydrated and mixed with the input sample when the input sample is conveyed from the sample input volume;

an amplification module coupled within the housing and configured to receive the input sample, the amplification module defining a reaction volume and including a heater, the amplification module configured to amplify a control nucleic acid within the positive control to produce a control amplicon along with amplification of a target nucleic acid within the input sample to produce a target amplicon;

a reagent stored within the housing, the reagent formulated to produce a first signal indicating a presence of the target amplicon and a second signal indicating a presence of the control amplicon; and

a detection module that receives an output produced by the amplification module including the target amplicon and the control amplicon, the detection module coupled within the housing and including a first detection surface and a second detection surface, the first detection surface configured to interact with the target amplicon such that when the detection module contains the reagent the first signal is produced from the first detection surface, the second detection surface configured to interact with the control amplicon such that when the detection module contains the reagent the second signal is produced from the second detection surface.

2. The apparatus of claim 1, wherein:

The first detection surface includes a first capture probe associated with the target amplicon; and

the second detection surface includes a second capture probe associated with the control amplicon.

3. The apparatus of claim 2, wherein the second detection surface includes the first capture probe and the second capture probe.

4. The apparatus of claim 1, wherein the solid positive control is a bead retained with a fluidic path of the sample input module.

5. The apparatus of claim 4, wherein the solid positive control is a gram negative organism.

6. The apparatus of claim 5, wherein the solid positive control includes any one of A. fischeri or N.suhflava.

7. The apparatus of claim 1, wherein the reagent is stored within a sealed container within the housing, the reagent being any one of a horseradish peroxidase enzyme with a streptavidin linker or a substrate formulated to produce the first signal when the substrate is contacted with the horseradish peroxidase enzyme with the streptavidin linker.

8. The apparatus of claim 7, wherein:

the first signal is a first visible signal produced from the first detection surface;

the second signal is a second visible signal produced from the second detection surface; and

the detection module is positioned within the housing such that the first visible signal and the second visible signal are viewable via a detection window of the housing.

9. The apparatus of claim 8, wherein the reagent is formulated such that the first visible signal is a non-fluorescent signal produced from the first detection surface without an excitation light source within the housing.

10. The apparatus of claim 1, wherein the apparatus is a molecular diagnostic test device and the housing defines a status opening, the apparatus further comprising:

a status light configured to emit a light signal associated with a status of the molecular diagnostic test device, the light signal visible via the status opening.

11. The apparatus of claim 1, wherein the amplification module includes a flow member that defines the reaction volume, the flow member constructed from at least one of a cyclic olefin copolymer or a graphite-based material and having a thickness of less than about 0.5 mm.

12. The apparatus of claim 1, wherein the reaction volume is a serpentine flow channel, and the heater is coupled to the serpentine flow channel, the apparatus further comprising:

a fluid pump within the housing, the fluid pump configured to generate, within the housing, a first force that causes a flow of the input sample within the serpentine flow channel and a second force that causes a flow of the reagent to the first detection surface.

13. An apparatus, comprising:

a housing;

a sample input module enclosed by the housing, the sample input module defining a sample input volume that receives an input sample;

a solid positive control within the sample input module, the solid positive control being nonpathogenic to humans and being rehydrated and mixed with the input sample when the input sample is conveyed from the sample input volume;

an amplification module coupled within the housing and configured to receive the input sample, the amplification module defining a reaction volume and including a heater, the amplification module configured to amplify a control nucleic acid within the positive control to produce a control amplicon along with amplification of a target nucleic acid within the input sample to produce a target amplicon;

a reagent module within the housing, the reagent module including a reagent container containing a reagent formulated to cause a first signal indicating a presence of the target amplicon and a second signal indicating a presence of the control amplicon to be produced; and

a detection module that receives an output produced by the amplification module including the target amplicon and the control amplicon, the detection module including a first detection surface and a second detection surface, the first detection surface configured to interact with the target amplicon such that when the reagent is conveyed into the detection module the first signal is produced from the first detection surface, the second detection surface configured to interact with the control amplicon such that when the reagent is conveyed into the detection module the second signal is produced from the second detection surface.

14. The apparatus of claim 13, wherein the reaction volume is a serpentine flow channel, the amplification module includes a flow member that defines the serpentine flow channel, and the heater is coupled to flow member to heat the serpentine flow channel, the apparatus further comprising:

a fluid pump within the housing, the fluid pump configured to generate a force that causes a flow of the input sample within the serpentine flow channel.

15. The apparatus of claim 14, wherein:

the force is a first force; and

the fluid pump is configured to generate a second force that causes a flow of the reagent from the reagent module into the detection module.

16. The apparatus of claim 14, further comprising:

a control module within the housing, the control module including a processor configured to regulate a power input to the fluid pump based on at least one of an encoder signal or a measured electrical signal such that the fluid pump produces a target flow rate of the input sample within the serpentine flow channel.

17. The apparatus of claim 14, wherein the heater is coupled to the flow member such that a first heating portion of the heater produces a first temperature zone within a first portion of the serpentine flow channel and a second heating portion of the heater produces a second temperature zone with a second portion of the serpentine flow channel, the first temperature zone and the second temperature zone maintained such that the flow of the input sample within the serpentine flow channel is thermally cycled.

18. The apparatus of claim 13, wherein the solid positive control is a bead retained with a fluidic path of the sample input module.

19. The apparatus of claim 18, wherein the solid positive control is a gram negative organism.

20. The apparatus of claim 19, wherein the solid positive control includes any one of A. fischeri or N.suhflava.

21. The apparatus of claim 13, wherein:

the first signal is a first visible signal produced from the first detection surface;

the second signal is a second visible signal produced from the second detection surface; and

the detection module is positioned within the housing such that the first visible signal and the second visible signal are viewable via a detection window of the housing.

22. The apparatus of claim 13, wherein the apparatus is a molecular diagnostic test device and the housing defines a status opening, the apparatus further comprising:

a status light configured to emit a light signal associated with a status of the molecular diagnostic test device, the light signal visible via the status opening; and

a control module within the housing, the control module including a processor configured to produce a variation in at least one of a duration of the light signal or a pattern of the light signal.

23. The apparatus of claim 13, wherein the housing, the amplification module, the reagent module, and the detection module are collectively configured for one and only one use and are disposable.

24. The apparatus of claim 13, wherein the apparatus is a molecular diagnostic test device that is a stand-alone molecular diagnostic test device configured to produce the first signal and the second signal without any external instrument.

25. The apparatus of claim 24, further comprising:

a power plug configured to couple the stand-alone molecular diagnostic test device to a power source; and

a sample transfer pipette configured to convey the input sample from a sample container into the sample input module.