Systems and Methods for Multiple Analyte Detection

Abstract

Systems and methods for multiple analyte detection include a system for distribution of a biological sample that includes a substrate, wherein the substrate includes a plurality of sample chambers, a sample introduction channel for each sample chamber, and a venting channel for each sample chamber. The system may further include a preloaded reagent contained in each sample chamber and configured for nucleic acid analysis of a biological sample that enters the substrate and a sealing instrument configured to be placed in contact with the substrate to seal each sample chamber so as to substantially prevent sample contained in each sample chamber from flowing out of each sample chamber. The substrate can be constructed of detection-compatible and assay-compatible materials.

1 . A system for distribution of a biological sample, the system comprising: 
 a substrate, wherein the substrate comprises a plurality of sample chambers, a sample introduction channel for each sample chamber, and a venting channel for each sample chamber;    a preloaded reagent contained in each sample chamber and configured for nucleic acid analysis of a biological sample that enters the substrate; and    a sealing instrument configured to be placed in contact with the substrate to seal each sample chamber so as to substantially prevent sample contained in each sample chamber from flowing out of each sample chamber,    wherein the substrate is constructed of detection-compatible and assay-compatible materials.    
     
     
         2 . The system of  claim 1 , wherein the sealing instrument is configured to be placed in contact with an exterior portion of the substrate.  
     
     
         3 . The system of  claim 1 , wherein the sealing instrument is configured to be placed in at least one of pressure contact and thermal contact with the substrate.  
     
     
         4 . The system of  claim 1 , wherein the sealing instrument is configured to seal the sample introduction channels and venting channels for each sample chamber.  
     
     
         5 . The system of  claim 1 , wherein the sealing instrument is configured to be placed in contact with the substrate at least one of before a reaction process that occurs in the sample chambers and during a reaction process that occurs in the sample chambers.  
     
     
         6 . The system of  claim 5 , wherein the sealing plate is configured to be placed in contact with the substrate before a reaction process that occurs in the sample chambers to seal each sample chamber.  
     
     
         7 . The system of  claim 5 , wherein the sealing plate is configured to be placed in contact with the substrate during a reaction process that occurs in the sample chambers to seal each sample chamber.  
     
     
         8 . The system of  claim 7 , further comprising a thermal block, wherein the thermal block comprises the sealing plate.  
     
     
         9 . The system of  claim 1 , wherein the sealing instrument comprises one of a plate and a roller.  
     
     
         10 . The system of  claim 1 , wherein the substrate comprises a film layer and wherein a portion of the film layer fills the sample introduction channels and the venting channels upon contact of the sealing instrument with the substrate.  
     
     
         11 . The system of  claim 1 , wherein the sealing instrument comprises a plurality of sealing protrusions.  
     
     
         12 . The system of  claim 11 , wherein the sealing protrusions are configured to seal the sample introduction channels and venting channels for each sample chamber.  
     
     
         13 . The system of  claim 11 , further comprising an additional sealing instrument, wherein the plurality of sealing protrusions comprises a first plurality of sealing protrusions associated with the sealing instrument and a second plurality of the sealing protrusions associated with the additional sealing instrument, the first plurality and second plurality of sealing protrusions being configured to seal differing groups of sample chambers when the sealing instrument and the additional sealing instrument are respectively placed in contact with the substrate.  
     
     
         14 . The system of  claim 13 , wherein the first plurality of sealing protrusions is configured to seal the sample introduction channels for each sample chamber and the second plurality of sealing protrusions are configured to seal the venting channels for each sample chamber.  
     
     
         15 . The system of  claim 11 , wherein each sealing protrusion is configured to contact a respective sample introduction channel and venting channel for each sample chamber when the sealing instrument is placed in contact with the substrate.  
     
     
         16 . The system of  claim 11 , wherein the plurality of sealing protrusions are configured to respectively align with the plurality of sample chambers.  
     
     
         17 . The system of  claim 16 , wherein each sample chamber is configured to receive a respective sealing protrusion such that the sealing protrusions seal the sealing chambers substantially at an inner peripheral surface defining each sample chamber.  
     
     
         18 . The system of  claim 11 , wherein the sealing instrument further comprises a plurality of optical apertures configured to provide optical access to the sample chambers.  
     
     
         19 . The system of  claim 18 , wherein the sealing protrusions are configured to pierce the substrate and enter the introduction and venting channels for each sample chamber.  
     
     
         20 . The system of  claim 11 , wherein the sealing protrusions comprise one of pins, disks, blades, and bumps.  
     
     
         21 . The system of  claim 1 , wherein the substrate further comprises a film layer and a base, and at least one venting mechanism configured to permit gas to escape the substrate.  
     
     
         22 . The system of  claim 21 , wherein the substrate further comprises a sample supply channel in fluid communication with a plurality of the sample introduction channels.  
     
     
         23 . The system of  claim 22 , wherein the sample supply channel comprises a serpentine portion.  
     
     
         24 . The system of  claim 22 , wherein the sample supply channel comprises a bifurcation.  
     
     
         25 . The system of  claim 22 , wherein the sample supply channel comprises a U-shape portion.  
     
     
         26 . The system of  claim 21 , wherein the substrate further comprises a plurality of sample supply channels, each sample supply channel being in flow communication with a differing group of sample introduction channels and corresponding sample chambers.  
     
     
         27 . The system of  claim 26 , wherein the substrate further comprises a plurality of sample inlet ports, each sample inlet port being in flow communication with a differing sample supply channel.  
     
     
         28 . The system of  claim 21 , wherein the at least one venting mechanism comprises a plurality of venting mechanisms respectively corresponding to the plurality of sample chambers.  
     
     
         29 . The system of  claim 21 , wherein the substrate further comprises a venting chamber in flow communication with each venting channel.  
     
     
         30 . The system of  claim 21 , wherein the substrate further comprises at least one overfill chamber corresponding to the at least one venting mechanism.  
     
     
         31 . The system of  claim 30 , further comprising a detector configured to detect sample in the overfill chamber.  
     
     
         32 . The system of  claim 31 , wherein the detector comprises one of an optical sensor, a refractive sensor, and a capacitance sensor.  
     
     
         33 . The system of  claim 30 , further comprising an additional venting mechanism disposed upstream of the at least one vent mechanism corresponding to the overfill chamber.  
     
     
         34 . The system of  claim 21 , wherein the substrate further comprises a venting chamber for each sample chamber, the venting chambers being in flow communication with the sample chambers via the venting channels, wherein the at least one venting mechanism comprises a plurality of venting mechanisms each corresponding to a respective venting chamber.  
     
     
         35 . The system of  claim 21 , wherein the substrate further comprises a main venting channel in flow communication with the venting channels.  
     
     
         36 . The system of  claim 35 , wherein the at least one venting mechanism comprises a porous fiber disposed in the main venting channel.  
     
     
         37 . The system of  claim 36 , wherein the fiber is a hollow fiber or a solid fiber.  
     
     
         38 . The system of  claim 21 , wherein the at least one venting mechanism comprises a gas-permeable or porous membrane.  
     
     
         39 . The system of  claim 38 , wherein the substrate further comprises a venting chamber for each sample chamber, the venting chambers being in flow communication with the sample chambers via the venting channels, each venting chamber being configured to receive a gas-permeable or porous membrane.  
     
     
         40 . The system of  claim 38 , wherein the gas-permeable or porous membrane is in contact with the film layer at a surface of the film facing away from the base.  
     
     
         41 . The system of  claim 40 , wherein the gas-permeable or porous membrane has a sheet-like or strip-like configuration.  
     
     
         42 . The system of  claim 41 , wherein the substrate further comprises a venting chamber for each sample chamber, the venting chambers being in flow communication with the sample chambers via the venting channels, and wherein the at least one gas-permeable or porous membrane corresponds to a plurality of venting chambers.  
     
     
         43 . The system of  claim 42 , wherein the at least one gas-permeable or porous membrane comprises a plurality of membranes, each membrane corresponding to differing groups of venting chambers.  
     
     
         44 . The system of  claim 40 , wherein the substrate further comprises an additional film layer, the film layers being disposed on opposing surfaces of the base.  
     
     
         45 . The system of  claim 44 , wherein the additional film layer and the base together define the sample chambers, sample introduction channels, and venting channels.  
     
     
         46 . The system of  claim 21 , wherein the at least one venting mechanism comprises at least one through hole in the substrate.  
     
     
         47 . The system of  claim 46 , wherein the at least one through hole is provided in one of the base and the film layer.  
     
     
         48 . The system of  claim 47 , wherein the at least one through hole is provided in the film layer and is configured to prevent sample from passing therethrough via capillarity.  
     
     
         49 . The system of  claim 21 , wherein the at least one venting mechanism is configured to substantially prevent sample from passing through the at least one venting mechanism and out of the substrate.  
     
     
         50 . A method for distribution of a biological sample, the method comprising: 
 providing a base, wherein the base comprises a plurality of sample cavities containing a preloaded reagent therein, a sample introduction trench for each sample cavity, and a venting trench for each sample cavity, and wherein the base is constructed of detection-compatible and assay-compatible materials;    providing a film to adhere to the base to form a substrate, wherein the film and base form a plurality of sample chambers from each sample cavity, a sample introduction channel from each sample introduction trench, and a venting channel from each sample venting trench;    supplying the biological sample to the substrate;    filling the sample chambers with the biological sample via the sample introduction channels;    passing gas out of the substrate via at least one venting mechanism in the substrate; and    sealing the sample chambers to substantially prevent sample in the sample chambers from flowing out of the sample chambers.    
     
     
         51 . The method of  claim 50 , wherein the sealing the sample chambers comprises placing a sealing instrument in contact with the substrate.  
     
     
         52 . The method of  claim 50 , wherein filling the sample chambers comprises at least one of spinning the substrate to provide centrifugal force, sizing the sample introductory channels to provide capillary force, and aspirating the sample through the vent channels.  
     
     
         53 . The method of  claim 50 , wherein filling the sample chambers comprises providing positive pressure to the sample.  
     
     
         54 . The method of  claim 53 , further comprising venting gas in the sample chamber through the venting channels and the at least one venting mechanism.  
     
     
         55 . The method of  claim 54 , wherein the venting mechanism comprises at least one gas-permeable or porous membrane.  
     
     
         56 . The method of  claim 50 , further comprising substantially preventing the sample from passing through the at least one venting mechanism and out of the substrate.  
     
     
         57 . The method of  claim 56 , wherein preventing the sample from passing through the at least one venting mechanism comprises holding the sample in the venting mechanism via capillarity.  
     
     
         58 . A system for distribution of a biological sample, the system comprising: 
 means for distributing the sample to a plurality of sample chambers containing a preloaded reagent;    means for venting each of the sample chambers; and    means for sealing each of the sample chambers.    
     
     
         59 . A device for testing a biological sample, the device comprising: 
 a substrate defining a plurality of distribution portions configured to distribute biological sample throughout the substrate, the plurality of distribution portions comprising a plurality of sample chambers, a sample introduction channel for each sample chamber, and a venting channel for each sample chamber; and    a substance disposed in at least one of the distribution portions, the substance being configured to seal each sample chamber so as to substantially prevent sample disposed in each sample chamber from flowing out of each sample chamber during testing of the biological sample.    
     
     
         60 . The device of  claim 59 , wherein the substance comprises one of an adhesive, a gas, a substance configured to dissolve into a gas upon contact with the biological sample, a fluid immiscible with the biological sample, an absorbent material, and porous hydrophobic material.  
     
     
         61 . The device of  claim 59 , wherein the substance is disposed in the sample introduction and venting channels for each sample chamber.  
     
     
         62 . The device of  claim 59 , wherein the plurality of distribution portions further comprises a vent chamber in flow communication with each venting channel and wherein the substance is disposed in each vent chamber.  
     
     
         63 . The device of  claim 59 , wherein the plurality of distribution portions further comprises a main fluid supply channel in flow communication with the sample introduction channels, and wherein the substance is disposed in the main fluid supply channel.  
     
     
         64 . The device of  claim 59 , wherein the substance is configured to seal each sample chamber upon sample contacting the substance.  
     
     
         65 . The device of  claim 59 , wherein the substance is configured to seal each sample chamber in response to elevating a temperature of the substrate during testing of the biological sample.