Devices and methods for molecular diagnostic testing

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.

What is claimed is: 
     
         1 . A single-use molecular diagnostic test device, comprising:
 a housing including a sample input port;   a sample preparation module within the housing, the sample preparation module defining a receiving volume in fluid communication with the sample input port, the receiving volume configured to receive a biological sample, the sample preparation module configured to react the biological sample with a lysis reagent to produce an input sample;   a sample lid coupled to the housing, the sample lid configured to move from a first position to a second position, the sample input port being accessible when the sample lid is in the first position, the sample input port being sealed closed when the sample lid is in the second position, the sample lid configured to irreversibly engage a portion of the housing when the sample lid is moved to the second position to lock the sample lid in the second position;   an amplification module within the housing, the amplification module configured to receive the input sample from the sample preparation module, the amplification module defining a reaction volume and including a heater, the amplification module configured to amplify a target nucleic acid within the input sample to produce an amplified output containing a target amplicon; and   a detection module within the housing, the detection module defining a detection channel and a detection surface within the detection channel, the detection channel configured to receive the amplified output from the amplification module and react the target amplicon within the amplified output with a detection reagent to produce a signal from the detection surface that indicates a presence of the target amplicon.   
     
     
         2 . The single-use molecular diagnostic test device of  claim 1 , wherein the signal is a non-fluorescent signal. 
     
     
         3 . The single-use molecular diagnostic test device of  claim 2 , wherein:
 the housing defines a detection window;   the signal is a visible signal; and   the visible signal is viewable via the detection window of the housing.   
     
     
         4 . The single-use molecular diagnostic test device of  claim 3 , wherein the detection surface includes a capture probe associated with the target amplicon. 
     
     
         5 . The single-use molecular diagnostic test device of  claim 3 , wherein the detection surface includes an absorbent member formulated to receive the amplified output produced by the amplification module, the visible signal being produced from the absorbent member. 
     
     
         6 . The single-use molecular diagnostic test device of  claim 3 , further comprising:
 a solid positive control that is nonpathogenic to humans and is mixed with the biological sample.   
     
     
         7 . The single-use molecular diagnostic test device of  claim 6 , wherein the solid positive control is within the receiving volume, the solid positive control being rehydrated and mixed with the input sample when the input sample is conveyed from the receiving volume toward the amplification module. 
     
     
         8 . The single-use molecular diagnostic test device of  claim 3 , wherein the amplification module is configured to heat the input sample through a plurality of thermal cycles to amplify the target nucleic acid. 
     
     
         9 . The single-use molecular diagnostic test device of  claim 3 , 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. 
     
     
         10 . The single-use molecular diagnostic test device of  claim 3 , wherein:
 the housing defines a status indicator, the status indicator configured to produce a status signal associated with a status of the single-use molecular diagnostic test device.   
     
     
         11 . The single-use molecular diagnostic test device of  claim 10 , wherein the status includes at least one of whether a tab has been removed from the housing, whether a diagnostic test is in process, whether an error state is present, and whether the diagnostic test is completed. 
     
     
         12 . The single-use molecular diagnostic test device of  claim 3 , wherein the sample preparation module includes an indicator to allow verification that a volume of the biological sample has been received within the receiving volume. 
     
     
         13 . A single-use molecular diagnostic test device, comprising:
 a housing including a sample input port;   a sample preparation module within the housing, the sample preparation module defining a receiving volume in fluid communication with the sample input port, the receiving volume configured to receive a biological sample, the sample preparation module including an indicator to allow verification that a volume of the biological sample has been received within the receiving volume;   a sample lid coupled to the housing, the sample lid configured to move from a first position to a second position, the sample input port being accessible when the sample lid is in the first position, the sample input port being sealed closed when the sample lid is in the second position, the sample lid configured to irreversibly engage a portion of the housing when the sample lid is moved to the second position to lock the sample lid in the second position;   an amplification module within the housing, the amplification module configured to receive the biological sample from the sample preparation module, the amplification module defining a reaction volume and including a heater, the amplification module configured to amplify a target nucleic acid within the biological sample to produce an amplified output containing a target amplicon; and   a detection module within the housing, the detection module defining a detection channel and a detection surface within the detection channel, the detection channel configured to receive the amplified output from the amplification module and react the target amplicon within the amplified output with a detection reagent to produce a signal from the detection surface that indicates a presence of the target amplicon.   
     
     
         14 . The single-use molecular diagnostic test device of  claim 13 , wherein the signal is a non-fluorescent signal produced without an excitation light source within the housing. 
     
     
         15 . The single-use molecular diagnostic test device of  claim 14 , wherein:
 the housing defines a detection window;   the signal is a visible signal; and   the visible signal is viewable via the detection window of the housing.   
     
     
         16 . The single-use molecular diagnostic test device of  claim 15 , wherein the visible signal remains visible via the detection window for at least about 30 minutes after first being produced. 
     
     
         17 . The single-use molecular diagnostic test device of  claim 15 , wherein the detection surface includes a capture probe associated with the target amplicon. 
     
     
         18 . The single-use molecular diagnostic test device of  claim 15 , wherein the detection surface includes an absorbent member formulated to receive the amplified output produced by the amplification module, the visible signal being produced from the absorbent member. 
     
     
         19 . The single-use molecular diagnostic test device of  claim 13 , wherein the amplification module is configured to heat the biological sample through a plurality of thermal cycles to amplify the target nucleic acid. 
     
     
         20 . The single-use molecular diagnostic test device of  claim 13 , wherein:
 the housing defines a status indicator, the status indicator configured to produce a status signal associated with a status of the single-use molecular diagnostic test device.   
     
     
         21 . A system for detecting the presence of a target nucleic acid, comprising:
 a single-use molecular diagnostic test device including a housing, a sample lid coupled to the housing, a sample preparation module, an amplification module and a detection module, the sample preparation module, the amplification module, and the detection module each being within the housing,
 the housing including a sample input port; 
 the sample lid coupled to the housing, the sample lid configured to move from a first position to a second position, the sample input port being accessible when the sample lid is in the first position, the sample input port being sealed closed when the sample lid is in the second position, the sample lid configured to irreversibly engage a portion of the housing when the sample lid is moved to the second position to lock the sample lid in the second position; 
 the sample preparation module defining a receiving volume in fluid communication with the sample input port, the receiving volume configured to receive a biological sample, the sample preparation module configured to react the biological sample with a lysis reagent to produce an input sample; 
 the amplification module configured to receive the input sample from the sample preparation module, the amplification module defining a reaction volume and including a heater, the amplification module configured to amplify the target nucleic acid within the input sample to produce an amplified output containing a target amplicon; and 
 the detection module defining a detection channel and a detection surface within the detection channel, the detection channel configured to receive the amplified output from the amplification module and react the target amplicon within the amplified output with a detection reagent to produce a signal from the detection surface that indicates a presence of the target amplicon; and 
   a power supply unit configured to supply power to the single-use molecular diagnostic test device, the power supply unit configured to be removably coupled to the single-use molecular diagnostic test device.