Devices and methods for molecular diagnostic testing

• US 10,279,346 B2
• Filed: 09/28/2018
• Issued: 05/07/2019
• Est. Priority Date: 12/31/2014
• Status: Active Grant

• Current Assignee: Visby Medical, Inc.
• Original Assignee: Click Diagnostics, 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:
  US16/145,826
• Publication Number:
  US 20190030532A1
• Time in Patent Office: 221 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. A method of detecting a target nucleic acid molecule using a molecular diagnostic test device, comprising:

conveying a biological sample from a sample input volume defined by a sample input module towards an amplification module to rehydrate and mix a solid control organism within the sample input volume with the biological sample to form an input solution, the solid control organism being nonpathogenic to humans, the sample input module and the amplification module each coupled within a housing of the molecular diagnostic test device, the amplification module defining a reaction volume and including a heater;

heating the input solution within at least a portion of the reaction volume via the heater to amplify a control nucleic acid within the control organism and the target nucleic acid molecule within the biological sample thereby producing an output solution containing a target amplicon and a control amplicon; and

reacting within a detection module within the housing each of A) the output solution and B) a reagent to produce a first signal indicating a presence of the target amplicon and a second signal indicating a presence of the control amplicon.

2. The method of claim 1, wherein the detection module includes a first detection surface and a second detection surface, the method further comprising:

conveying the output solution into the detection module such that the first detection surface interacts with the target amplicon and the second detection surface interacts with the control amplicon, the first signal being produced from the first detection surface, the second signal being produced from the second detection surface.

3. The method of claim 1, wherein the solid control organism is a bead retained with a fluidic path of the sample input module.

4. The method of claim 2, wherein the reacting includes:

producing a first flow of the output solution across the first detection surface and the second detection surface; and

producing a second flow of the reagent across the first detection surface and the second detection surface.

5. The method of claim 4, wherein the producing the first flow and the second flow is performed by a fluid pump disposed within the housing of the molecular diagnostic test device.

6. The method of claim 1, wherein the detection module includes an absorbent member formulated to receive the output solution produced by the amplification module, including the target amplicon and the control amplicon.

7. The method of claim 1, further comprising:

emitting, from a status light of the molecular diagnostic test device, a light signal associated with a status of the molecular diagnostic test device, the light signal visible via a status opening defined by the housing of the molecular diagnostic test device.

8. The method of claim 4, wherein:

the amplification module includes a flow member that defines the reaction volume, the reaction volume being a serpentine flow channel; and

the heating includes;

heating a first heating portion of the heater to produce a first temperature zone within a first portion of the serpentine flow channel;

heating a second heating portion of the heater to produce a second temperature zone with a second portion of the serpentine flow channel; and

producing a flow of the input solution within the serpentine flow channel to thermally cycle the input solution between the first temperature zone and the second temperature zone.

9. The method of claim 1, wherein the reagent is formulated such that the first signal is a non-fluorescent visible signal produced without an excitation light source within the housing of the molecular diagnostic test device.

10. A method of detecting a target nucleic acid molecule using a molecular diagnostic test device, comprising:

conveying a biological sample into a sample preparation module within the molecular diagnostic test device; and

actuating the molecular diagnostic test device to cause the molecular diagnostic test device to;

convey the biological sample from a sample input volume defined by the sample preparation module towards an amplification module such that a solid control organism within the sample input volume is mixed with the biological sample to form an input solution, the solid control organism being nonpathogenic to humans, the amplification module defining a reaction volume and including a heater;

heat the input solution within the reaction volume via the heater through at least 30 thermal cycles to amplify a control nucleic acid within the control organism and the target nucleic acid molecule within the biological sample thereby producing an output solution containing a target amplicon and a control amplicon; and

react within a detection module within the molecular diagnostic test device each of A) the output solution and B) a reagent to produce a first signal indicating a presence of the target amplicon and a second signal indicating a presence of the control amplicon.

11. The method of claim 10, further comprising:

reading a result associated with at least one of the first signal or the second signal; and

discarding, after the reading, the molecular diagnostic test device.

12. The method of claim 11, wherein the reading includes viewing, through a detection window defined by a housing of the molecular diagnostic test device, the first signal and the second signal.

13. The method of claim 10, wherein:

the actuating the molecular diagnostic test device includes manipulating an actuator coupled to a housing of the molecular diagnostic test device, a switch of a control module within the housing being actuated in response to movement of the actuator, the control module providing power from a power source to the heater when the switch is actuated.

14. The method of claim 10, wherein a volume of the output solution produced by the amplification module is at least about 75 μ

l.

15. The method of claim 10, wherein the solid control organism is a bead retained with a fluidic path of the sample preparation module.

16. The method of claim 10, wherein the actuating the molecular diagnostic test device causes a status light of the molecular diagnostic test device to emit a light signal associated with a status of the molecular diagnostic test device.