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WO2018126119A1 - Dispositif de capture et de traitement d'aérosol - Google Patents

Dispositif de capture et de traitement d'aérosol Download PDF

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Publication number
WO2018126119A1
WO2018126119A1 PCT/US2017/068929 US2017068929W WO2018126119A1 WO 2018126119 A1 WO2018126119 A1 WO 2018126119A1 US 2017068929 W US2017068929 W US 2017068929W WO 2018126119 A1 WO2018126119 A1 WO 2018126119A1
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WO
WIPO (PCT)
Prior art keywords
sample chamber
collection device
sample
protrusions
aerosolized
Prior art date
Application number
PCT/US2017/068929
Other languages
English (en)
Inventor
Luke P. Lee
Original Assignee
Lee Luke P
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Lee Luke P filed Critical Lee Luke P
Publication of WO2018126119A1 publication Critical patent/WO2018126119A1/fr

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Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00—Sampling; Preparing specimens for investigation
    • G01N1/02—Devices for withdrawing samples
    • G01N1/22—Devices for withdrawing samples in the gaseous state
    • G01N1/2202—Devices for withdrawing samples in the gaseous state involving separation of sample components during sampling
    • G01N1/2208—Devices for withdrawing samples in the gaseous state involving separation of sample components during sampling with impactors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
    • A61B5/0071—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence by measuring fluorescence emission
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/08—Measuring devices for evaluating the respiratory organs
    • A61B5/082—Evaluation by breath analysis, e.g. determination of the chemical composition of exhaled breath
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/08—Measuring devices for evaluating the respiratory organs
    • A61B5/097—Devices for facilitating collection of breath or for directing breath into or through measuring devices
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue
    • A61B5/14507—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue specially adapted for measuring characteristics of body fluids other than blood
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00—Sampling; Preparing specimens for investigation
    • G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
    • G01N1/40—Concentrating samples
    • G01N1/405—Concentrating samples by adsorption or absorption
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/483—Physical analysis of biological material
    • G01N33/497—Physical analysis of biological material of gaseous biological material, e.g. breath
    • G01N33/4975—Physical analysis of biological material of gaseous biological material, e.g. breath other than oxygen, carbon dioxide or alcohol, e.g. organic vapours
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00—Sampling; Preparing specimens for investigation
    • G01N1/02—Devices for withdrawing samples
    • G01N1/22—Devices for withdrawing samples in the gaseous state
    • G01N1/2202—Devices for withdrawing samples in the gaseous state involving separation of sample components during sampling
    • G01N2001/222—Other features
    • G01N2001/2223—Other features aerosol sampling devices
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00—Sampling; Preparing specimens for investigation
    • G01N1/02—Devices for withdrawing samples
    • G01N1/22—Devices for withdrawing samples in the gaseous state
    • G01N2001/2244—Exhaled gas, e.g. alcohol detecting

Definitions

  • NA nucleic acids
  • DNA deoxyribonucleic acid
  • RNA ribonucleic acid
  • miRNA micro RNA
  • exosome-microRNA exosome-microRNA
  • FIG. 1 is schematic diagram depicting an aerosolized collection, amplification, and analysis system according to certain aspects of the present disclosure.
  • FIG. 2 is an isometric diagram depicting an aerosolized sample collection device according to certain aspects of the present disclosure.
  • FIG. 3 is a partial cutaway isometric diagram depicting an aerosolized sample collection device according to certain aspects of the present disclosure.
  • FIG. 4 is a front view depicting an aerosolized sample collection device according to certain aspects of the present disclosure.
  • FIG. 5 is a side view depicting an aerosolized sample collection device according to certain aspects of the present disclosure.
  • FIG. 6 is a cutaway side view taken along line B:B of FIG. 2 depicting an aerosolized sample collection device according to certain aspects of the present disclosure.
  • FIG. 7 is a cutaway front view taken along line A:A of FIG. 2 depicting an aerosolized sample collection device according to certain aspects of the present disclosure.
  • FIG. 8 is a schematic side view depicting a protrusion array with upper and lower protrusions extending across most of the thickness of an aerosolized sample collection device according to certain aspects of the present disclosure.
  • FIG. 9 is a schematic side view depicting a protrusion array with protrusions extending fully across the thickness of an aerosolized sample collection device according to certain aspects of the present disclosure.
  • FIG. 10 is a schematic side view depicting a protrusion array with rounded, lower protrusions extending across most of the thickness of an aerosolized sample collection device according to certain aspects of the present disclosure.
  • FIG. 11 is a schematic side view depicting a protrusion array with pyramidal upper and lower protrusions extending across most of the thickness of an aerosolized sample collection device according to certain aspects of the present disclosure.
  • FIG. 12 is a cutaway top view taken along line C:C of FIG. 2 depicting an aerosolized sample collection device according to certain aspects of the present disclosure.
  • FIG. 13 is a top view depicting a lower protrusion according to certain aspects of the present disclosure.
  • FIG. 14 is a cutaway side view depicting the top portion of a lower protrusion according to certain aspects of the present disclosure.
  • FIG. 15 is a schematic side view depicting an analysis system for detecting radiation emitted from an aerosolized sample collection device prepared with multiple primers according to certain aspects of the present disclosure.
  • FIG. 16 is a flowchart depicting a process for collecting, amplifying, and analyzing a sample using an aerosolized sample collection device according to certain aspects of the present disclosure.
  • FIG. 17 is a schematic diagram depicting use of an aerosolized collection device according to certain aspects of the present disclosure.
  • FIG. 18 is a schematic diagram depicting an aerosolized collection device according to certain aspects of the present disclosure.
  • FIG. 19 is a schematic diagram depicting a process of collecting and amplifying NA samples using an aerosolized collection device according to certain aspects of the present disclosure.
  • FIG. 20 is a schematic diagram depicting processing of NA samples using an aerosolized collection device and processing device according to certain aspects of the present disclosure.
  • FIG. 21 is a set of diagrams depicting fluid flow through a cavity of an aerosolized collection device having domes of various heights according to certain aspects of the present disclosure.
  • FIG. 22 is a set of charts depicting normalized particle concentration in the cavity of FIG. 22 at various inlet fluid flow velocities, depicting normalized particle concentration (C p ) as a function of time (seconds) for various dome heights according to certain aspects of the present disclosure.
  • FIG. 23 is a set of charts depicting residence time statistics in the cavity of
  • FIG. 22 depicting residence time statistics as functions of inlet fluid flow velocities for various dome heights according to certain aspects of the present disclosure.
  • FIG. 24 is an axonometric diagram depicting flow through a long side of an array of cavities in an aerosolized collection device according to certain aspects of the present disclosure.
  • FIG. 25 is a top-view flow diagram depicting flow through the array of cavities of FIG. 24 according to certain aspects of the present disclosure.
  • FIG. 26 is a flow diagram depicting the fluid flow through the array of cavities of FIG. 24 taken along a plane just beyond the height of the dome according to certain aspects of the present disclosure.
  • FIG. 27 is a flow diagram depicting the fluid flow through the array of cavities of FIG. 24 taken along a plane intersecting the dome according to certain aspects of the present disclosure.
  • FIG. 28 is a flow diagram depicting the fluid flow through the array of cavities of FIG. 24 taken along a plane intersecting the dome and intersecting more of the dome than the plane of FIG. 27 according to certain aspects of the present disclosure.
  • FIG. 29 is a flow diagram depicting the fluid flow through the array of cavities of FIG. 24 taken along a plane just beyond the height of the dome according to certain aspects of the present disclosure.
  • FIG. 30 is a flow diagram depicting the fluid flow through the array of cavities of FIG. 24 taken along a plane intersecting the dome according to certain aspects of the present disclosure.
  • FIG. 31 is a flow diagram depicting the fluid flow through the array of cavities of FIG. 24 taken along a plane intersecting the dome and intersecting more of the dome than the plane of FIG. 30 according to certain aspects of the present disclosure.
  • FIG. 32 is an axonometric diagram depicting flow through a long side of an array of cavities in an aerosolized collection device according to certain aspects of the present disclosure.
  • FIG. 33 is a top-view flow diagram depicting flow through the array of cavities of FIG. 32 according to certain aspects of the present disclosure.
  • FIG. 34 is a flow diagram depicting the fluid flow through the array of cavities of FIG. 32 taken along a plane just beyond the height of the dome according to certain aspects of the present disclosure.
  • FIG. 35 is a flow diagram depicting the fluid flow through the array of cavities of FIG. 32 taken along a plane intersecting the dome according to certain aspects of the present disclosure.
  • FIG. 36 is a flow diagram depicting the fluid flow through the array of cavities of FIG. 32 taken along a plane intersecting the dome and intersecting more of the dome than the plane of FIG. 35 according to certain aspects of the present disclosure.
  • FIG. 37 is a flow diagram depicting the fluid flow through the array of cavities of FIG. 32 taken along a plane just beyond the height of the dome according to certain aspects of the present disclosure.
  • FIG. 38 is a flow diagram depicting the fluid flow through the array of cavities of FIG. 32 taken along a plane intersecting the dome according to certain aspects of the present disclosure.
  • FIG. 39 is a flow diagram depicting the fluid flow through the array of cavities of FIG. 32 taken along a plane intersecting the dome and intersecting more of the dome than the plane of FIG. 38 according to certain aspects of the present disclosure.
  • FIG. 40 is a set of illustrations depicting central fluid flow through a cylindrical chamber of an aerosolized collection device according to certain aspects of the present disclosure.
  • FIG. 41 is a set of illustrations depicting cross fluid flow through a cylindrical chamber of an aerosolized collection device according to certain aspects of the present disclosure.
  • FIG. 42 is a set of illustrations depicting offset fluid flow through a cylindrical chamber of an aerosolized collection device according to certain aspects of the present disclosure.
  • FIG. 43 is a set of illustrations depicting central fluid flow through a spherical chamber of an aerosolized collection device according to certain aspects of the present disclosure.
  • FIG. 44 is a set of illustrations depicting cross fluid flow through a spherical chamber of an aerosolized collection device according to certain aspects of the present disclosure.
  • FIG. 45 is a set of illustrations depicting offset fluid flow through a spherical chamber of an aerosolized collection device according to certain aspects of the present disclosure.
  • FIG. 46 is an axonometric flow diagram depicting fluid flow through a series of closely offset spherical chambers of an aerosolized collection device according to certain aspects of the present disclosure.
  • FIG. 47 is a cross-sectional flow diagram depicting fluid flow through the series of closely offset spherical chambers of FIG. 46 according to certain aspects of the present disclosure.
  • FIG. 48 is an axonometric flow diagram depicting fluid flow through a series of offset spherical chambers of an aerosolized collection device according to certain aspects of the present disclosure.
  • FIG. 49 is a cross-sectional flow diagram depicting fluid flow through the series of offset spherical chambers of FIG. 48 according to certain aspects of the present disclosure.
  • FIG. 50 is an axonometric flow diagram depicting fluid flow through a series of parallel-offset spherical chambers of an aerosolized collection device according to certain aspects of the present disclosure.
  • FIG. 51 is a cross-sectional flow diagram depicting fluid flow through the series of parallel-offset spherical chambers of FIG. 50 according to certain aspects of the present disclosure.
  • FIG. 52 is a schematic view and close-up view of a serialized array of chambers of an aerosolized collection device according to certain aspects of the present disclosure.
  • FIG. 53 is a schematic view and close-up view of an interconnected array of chambers of an aerosolized collection device according to certain aspects of the present disclosure.
  • FIG. 54 is an axonometric diagram depicting a clamshell-style aerosolized collection device according to certain aspects of the present disclosure.
  • FIG. 55 is a top view depicting the bottom body of the clamshell aerosolized collection device of FIG. 54 according to certain aspects of the present disclosure.
  • FIG. 56 is a see-through, side view depicting the clamshell aerosolized collection device of FIG. 54 according to certain aspects of the present disclosure.
  • FIG. 57 is a cross-sectional side view of an aerosolized collection device according to certain aspects of the present disclosure.
  • Certain aspects and features of the present disclosure relate to a device for collecting, amplifying, and analyzing an aerosolized sample containing genetic material, such as DNA, RNA, miRNA, or exosome-microRNA.
  • the device can contain an array of internal protrusions designed to capture genetic material from an aerosolized sample passing through an internal sample chamber of the device.
  • the internal protrusions are designed and arranged to provide a large surface area within the device.
  • PCR polymerase chain reaction
  • the device can be prepared to include any desired primers and/or other materials, or such materials can be added after sample collection.
  • the collection device can include equipment for performing thermal cycling without a separate thermal cycler. After undergoing amplification, the entire device can be placed in an instrument for analysis, such as through measurement of fluorescence.
  • the device including the internal protrusions, can be made from or include a plasmonic layer protected by a coating (e.g., S1O2 or A1 2 0 3 ), which can help avoid fluorescent quenching during analysis.
  • the entire device can provide a quick, accurate, easy, efficient, and disposable solution for analyzing genetic material in an aerosolized sample.
  • the device enables new, non-invasive methods for detecting NA biomarkers, for rapid and accurate identifications of pathogens, or for other molecular diagnostics of diseases or research uses.
  • the device is able to capture aerosol samples (e.g., collected from a patient's exhaled breath condensate), amplify any NAs present in the sample using PCR amplification, and optionally detect one or more DNA analyte(s) of interest, such as using fluorescent probes.
  • Exhaled breadth condensate (EBC) can include water vapor, water- soluble substances (e.g., around 99%), and insoluble substances (e.g., around 1%). Insoluble substances entrained in the EBC can accumulate in the collection device.
  • the device can be hand-held in size, or any other suitable size.
  • the device can be made from materials suitable for exposure to the thermal cycling and temperatures used for PCR amplification. For example, the device can be made using materials suitable for withstanding temperatures between at or below approximately 50° C or potentially at or below approximately 4° C, as well as at or above approximately 96° C or potentially as at or above approximately 98° C.
  • the sample collection device disclosed herein can be used to collect genetic material from an aerosol sample.
  • aerosol samples can include exhaled breath or an atmosphere in an environment (e.g., a hospital room).
  • the device can be used to collect genetic material from any fluid sample, such as a gas-borne or liquid-borne sample.
  • the sample collection device includes a sample chamber having an inlet and an outlet.
  • the aerosolized sample e.g., exhaled breath
  • the sample may be pressurized through positive pressure (e.g., force of a user exhaling into the inlet) or negative pressure (e.g., a vacuum source coupled to the outlet).
  • the inlet and outlet are located on opposite sides of the collection device, but they can be located in any suitable location, including on the same side of the collection device.
  • the sample chamber - and thus the collection device itself - can be dimensioned to have a length (e.g., between the inlet and outlet) that is longer than its width.
  • the sample chamber can include one or more internal walls to facilitate the aerosol sample passing through as much of the sample chamber as possible before exiting through the outlet.
  • the sample collection device can include an array of protrusions within the sample chamber.
  • the protrusions can be positioned to define a tortuous path through the sample chamber.
  • the protrusions can take any suitable form and can be designed to increase the collection device's surface area exposed to an aerosolized sample passing through the collection device.
  • the protrusions include upper and lower protrusions extending from the top and bottom of the sample chamber, respectively, but not completely spanning the height of the sample chamber.
  • the protrusions include protrusions that extend completely between the top and bottom of the sample chamber.
  • the protrusions are circular in shape, however they may take any suitable shape, including square, rectangular, triangular, cylindrical, spherical, cubical, pyramidal, conical, or any other suitable shape.
  • the protrusions can have widths on the micrometer or millimeter scale. In some cases, the distance between adjacent protrusions can be on the micrometer to millimeter scale.
  • the height of the protrusions can depend on the height of the sample chamber, but may be on the millimeter to centimeter scale. In some cases, any or all dimensions of the protrusions (e.g., height) and/or the protrusion array (e.g., distance between protrusions) can remain constant throughout the sample chamber. In other cases, the dimensions of the protrusions and/or the protrusion array can vary across one or more dimensions of the sample chamber.
  • protrusions extend in a direction perpendicular to the direction of travel of the aerosolized sample through the sample chamber.
  • protrusions can extend between the top and bottom of the sample chamber in a direction parallel to the height of the sample chamber.
  • protrusions can extend in other directions, such as laterally between sides of the sample chamber, or at acute or oblique angles to the walls (e.g., top, bottom, or sides) of the sample chamber.
  • a protrusion array can be a web of interconnecting protrusions.
  • protrusion can mean an element that extends from a wall of the sample chamber, such as a side wall, a top wall, or a bottom wall. In some cases, a protrusion can extend from another protrusion. In some cases, a protrusion can include a discrete item placed in the sample chamber and adhered to or otherwise affixed to a wall of the sample chamber.
  • a protrusion array can include a fixed, repeating pattern of protrusions.
  • a protrusion array can include adjacent, offset rows of spaced-apart protrusions.
  • a protrusion array can include a random or pseudo-random pattern.
  • the protrusion array can be engineered to establish a standing wave pattern within the sample chamber when an aerosol sample is pressurized through the sample chamber (e.g., by a user blowing). The standing wave pattern can facilitate sample collection in some cases.
  • the protrusion array can be engineered to disrupt any standing wave patterns within the sample chamber when an aerosol sample is pressurized through the sample chamber (e.g., by a user blowing). Disruption of standing wave patterns can facilitate sample collection in some cases.
  • the complexity, density, and/or arrangement of the protrusion array within the sample chamber can dictate the pressure resistance that must be overcome to successfully pass an aerosol sample through the collection device (e.g., by a user blowing through it).
  • Collection devices can be sold and/or labeled according to this pressure resistance that is to be overcome.
  • an appropriate collection device can be selected. For example, a patient without strong breath support may be given a collection device with a low pressure resistance, which may require multiple sample collection attempts, whereas a patient with strong breath support may be given a collection device with a higher pressure resistance, which may require fewer sample collection attempts.
  • a collection device used with a vacuum source can be selected to have a pressure resistance that appropriately matches the vacuum source.
  • the protrusions of the device can be made of or can include a layer of a material suitable for reflecting, amplifying, resonating, or otherwise improving the radiation emitted within the sample chamber (e.g., by DNA probes) that is desired to be measured in an analysis step.
  • the plasmonic layer is integrated for rapid and accurate photonic PCR, which allows LED light pulses to control for effective heat- transfer and PCR thermal cycle. For example, it is often desirable for light to be measured during an analysis step (e.g., fluorescent analysis), and thus the protrusions and walls can be made of materials designed to inhibit fluorescent quenching.
  • the protrusions of the device, as well as any walls of the device, can be made of or can include a layer of plasmonic material.
  • the plasmonic material can be selected from any suitable plasmonic material, including gold, aluminum, or other such plasmonic materials.
  • the plasmonic material can be gold nanoparticles. Plasmonic materials can improve photothermal heating, enabling fast and efficient polymerized chain reactions for NA amplification.
  • the protrusions of the device, as well as any walls of the device can be further covered in a protective layer.
  • the protective layer can be located over the plasmonic material.
  • the protective layer can be made of any suitable material, such as Silicon Dioxide (S1O2) or Aluminum Oxide (A1 2 0 3 ).
  • S1O2 Silicon Dioxide
  • A1 2 0 3 Aluminum Oxide
  • the protective layer can help inhibit fluorescence quenching.
  • the protective layer can be directly exposed to the aerosol sample when the aerosol sample is pressurized through the collection device.
  • the collection device can include a window suitable for allowing radiation to pass from the sample chamber to the analysis machine.
  • the window can be an optically transparent window.
  • the window can be transparent to the specific form of radiation being measured without necessarily being optically transparent.
  • the window can be placed on any of the walls of the device and on more than one wall of the device.
  • the window can occupy up to 100% of a wall of the device (e.g., one wall of the device can be made from an optically transparent material), or can occupy less than 100% of a wall of the device (e.g., the window is surrounded by a bezel of the material of the wall).
  • different primers specific for different DNA sequences can be immobilized within separate regions of the sample chamber.
  • Such a multiplexed collection device can undergo normal collection and amplification procedures and then undergo a multiplex analysis procedure, wherein the analysis machine is capable of detecting and/or measuring the presence of different DNA sequences based on measurements taken of the separate regions of the sample chamber.
  • the separate regions need not be fluidly isolated from one another.
  • Primers can be immobilized in the separate regions during manufacturing, immediately prior to sample collection, or prior to amplification.
  • a sample can be collected by having a patient blow into the inlet of the collection device, either directly or through a mouthpiece (e.g., a disposable and/or removable mouthpiece). DNA in the sample can be absorbed into the internal surfaces in the sample chamber and excess aerosol can exit through the outlet.
  • the sample collection process can be performed once or repeated multiple times.
  • the inlet and outlet can be sealed or otherwise covered after sample collection. In some cases, the inlet and outlet can be sealed prior to sample collection, such as to maintain sterility.
  • PCR reagents can be added to the interior of the device (e.g., prior to sealing the inlet and/or outlet or through another opening).
  • PCR reagents can be added to the sample chamber prior to sample collection, such as during manufacture or immediately prior to sample collection.
  • the entire collection device can be treated according to standard PCR protocols to amplify the DNA collected in the sample chamber.
  • the collection device can be manually processed or can be placed in an automated PCR machine (e.g., a thermal cycler). In some cases, the collection device can be placed into a custom-fit PCR machine or a custom-fit adaptor for a standard PCR machine.
  • the collection device can be also used to amplify and detect genetic material derived from organisms found in an aerosolized sample with the use of a lysing agent to lyse the cellular membranes of those organisms.
  • the lysing agent can be added to the aerosolized sample prior to collection or can be introduced directly to the sample chamber, such as during manufacture, immediately prior to sample collection, during sample collection (e.g., via the same inlet or a separate inlet), or after sample collection.
  • the collection device 102 can be placed in a PCR machine 110 (e.g., a thermal cycler).
  • PCR reagents can be added to the sample chamber after sample collection if PCR reagents were not previously placed into the sample chamber.
  • the entire collection device 102 can be heated and cooled as necessary to perform standard PCR amplification of the genetic material collected within, without needing to remove the sample from the sample chamber.
  • the collection device 102 can be placed in or adjacent to an analysis machine 112 (e.g., a fluorescence reader).
  • the analysis machine 112 can detect radiation 114, such as visible light. Radiation 114 (e.g., visible or non-visible light), can be emitted from DNA probes and collected by sensors of the analysis machine 112.
  • FIG. 2 is an isometric diagram depicting an aerosolized sample collection device 200 according to certain aspects of the present disclosure.
  • the sample collection device 200 can be collection device 102 of FIG. 1.
  • the collection device 200 includes a main body 216 having an inlet 218 and an outlet.
  • the main body 216 can comprise any suitable number of walls and can take any number of suitable shapes. In some cases, the main body 216 is rectangular in shape, having a top wall, a bottom wall, and side walls.
  • the walls can be made of or can include a plasmonic material.
  • the walls can be made of plastic with an internal layer of plasmonic material.
  • a layer of protective material can cover the inner surfaces of the plasmonic material.
  • the collection device 200 includes a window 220 that allows radiation to pass between the inside of the collection device 200 and outside the collection device 200.
  • a sample chamber inside the collection device 200 includes an array of protrusions 222.
  • the array of protrusions 222 can increase the surface area exposed to aerosolized samples being passed into the inlet 218, through the sample chamber, and out the outlet of the collection device 200.
  • the collection device 200 can take any suitable shape or form and be any suitable size. However, in some cases, the collection device 200 can take a form and/or shape that approximately resembles a deck of playing cards, allowing the collection device 200 to be easily handled and manipulated by a user.
  • FIG. 3 is a partial cutaway isometric diagram depicting an aerosolized sample collection device 300 according to certain aspects of the present disclosure.
  • the sample collection device 300 can be similar to the sample collection device 200 of FIG. 2.
  • the main body 316 of the sample collection device 300 is shown in partial cutaway, depicting an array of protrusions 322 within a sample chamber 328 of the sample collection device 300.
  • the array of protrusions 322 can take the form of a repeating pattern of protrusions 322 or may be random.
  • the array of protrusions 322 can include protrusions extending from the top and/or the bottom of the sample chamber 328. In some cases, interior walls (not shown) can divert an aerosolized sample being pressurized through the sample chamber 328 so that the aerosolized sample contacts more surfaces within the sample chamber 328.
  • FIG. 6 is a cutaway side view taken along line B:B of FIG. 2 depicting an aerosolized sample collection device 600 according to certain aspects of the present disclosure.
  • the sample collection device 600 can be the same as collection device 200 of FIG. 2.
  • the main body 616 is seen surrounding a sample chamber 626.
  • An opening 636 is formed in a top wall of the main body 616, into which a window 620 can be secured.
  • the sample chamber 626 includes an array of protrusions 622, which can include lower protrusions 632 and upper protrusions 634.
  • Lower protrusions 632 can extend upwards from the bottom wall of the main body 616, whereas upper protrusions 634 can extend downwards from the top wall of the main body 616.
  • the lower protrusions 632 can extend upwards from the bottom wall of the main body 616 by a height 638, but remain spaced apart from the top wall of the main body 616 by a gap 642.
  • the upper protrusions 634 can extend downwards from the top wall of the main body 616 by a height 640, but remain spaced apart from the bottom wall of the main body 616 by a gap 644.
  • the heights 638, 640 can extend at least approximately 50%, 55%, 60%, 65%, 70%, 75% 80%, 85%, 90% or 95% of the height within the sample chamber 626.
  • the main body 616 consists of a plasmonic material 628, such as gold or aluminum.
  • the main body 616 can by layered and can include a base outer material in addition to the plasmonic material 628.
  • the plasmonic material 628 can be coated by a protective layer 630.
  • the protective layer 630 can be made of any suitable material, such as, but not limited to, S1O2 or A1 2 0 3 .
  • FIG. 7 is a cutaway front view taken along line A:A of FIG. 2 depicting an aerosolized sample collection device 700 according to certain aspects of the present disclosure.
  • the sample collection device 700 can be the collection device 200 of FIG. 2.
  • the main body 716 is seen surrounding a sample chamber 726.
  • An opening 736 exists in a top wall of the main body 716, into which a window 720 can be secured.
  • the outlet 724 can be seen beyond the array of protrusions 722.
  • the sample chamber 726 can include an array of protrusions 722, which can include lower protrusions 732 and upper protrusions 734.
  • Lower protrusions 732 can extend upwards from the bottom wall of the main body 716, whereas upper protrusions 734 can extend downwards from the top wall of the main body 716.
  • the lower protrusions 732 can extend upwards from the bottom wall of the main body 716 by a height 738, but remain spaced apart from the top wall of the main body 716 by a gap 742.
  • the upper protrusions 734 can extend downwards from the top wall of the main body 716 by a height 740, but remain spaced apart from the bottom wall of the main body 716 by a gap 744.
  • the heights 738, 740 can extend at least approximately 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90% or 95% of the height within the sample chamber 726.
  • FIG. 9 is a schematic side view depicting a protrusion array 922 with protrusions 933 extending fully across the thickness of an aerosolized sample collection device 900 according to certain aspects of the present disclosure.
  • the protrusion array 922 can be used in a sample collection device 900 such as collection device 102 of FIG. 1.
  • the protrusions 933 can extend between the top and bottom walls of the sample chamber of the sample collection device 900.
  • Protrusions 933 can have any suitable shape, such as cylindrical, rectangular, or other.
  • FIG. 10 is a schematic side view depicting a protrusion array 1022 with rounded, lower protrusions 1032 extending across most of the thickness of an aerosolized sample collection device 1000 according to certain aspects of the present disclosure.
  • the protrusion array 1022 can be used in a sample collection device 1000 such as collection device 102 of FIG. 1.
  • the lower protrusions 1032 can extend from the bottom wall of the sample chamber of the sample collection device 1000.
  • the lower protrusions 1032 can have rounded ends.
  • Lower protrusions 1032 can take any suitable form, such as cylindrical, rectangular, or other shapes.
  • an array of protrusions, such as protrusion array 1022 may only contain protrusions extending from the wall opposite the opening or window of the collection device. For example, if the collection device includes a window on its upper wall, the array of protrusions may include only lower protrusions.
  • FIG. 11 is a schematic side view depicting a protrusion array 1122 with pyramidal upper and lower protrusions 1134, 1132 extending across most of the thickness of an aerosolized sample collection device 1100 according to certain aspects of the present disclosure.
  • the protrusion array 1122 can be used in a sample collection device 1100 such as collection device 102 of FIG. 1.
  • the protrusion array 1122 can include lower protrusions 1132 extending from the bottom wall of the sample chamber of the sample collection device 1100 and upper protrusions 1134 extending from the top wall of the sample chamber of the sample collection device 1100.
  • the lower and upper protrusions 1132, 1134 can be conical or pyramidal in shape, although they may take other shapes.
  • FIG. 12 is a cutaway top view taken along line C:C of FIG. 2 depicting an aerosolized sample collection device 1200 according to certain aspects of the present disclosure.
  • the sample collection device 1200 can be the same as collection device 200 of FIG. 2.
  • the main body 1216 is seen surrounding a sample chamber 1226.
  • An inlet 1218 and an outlet 1224 provide fluid access to the sample chamber 1226.
  • the main body 1216 consists of a plasmonic material 1228, such as, but not limited to, gold or aluminum.
  • the main body 1216 can by layered and can include a base outer material in addition to the plasmonic material 1228.
  • the plasmonic material 1228 can be coated by a protective layer 1230.
  • the protective layer 1230 can be made of any suitable material, such as, but not limited to, S1O2 or A1 2 0 3 .
  • the array of protrusions 1222 can include repeated patterns of protrusions, such as the lattice pattern depicted in FIG. 12. In some cases, other patterns can be used, or the array of protrusions 1222 can include a random or pseudo-random arrangement of protrusions.
  • the protective layer 1346 is an extension of the protective layer of the main body of a collection device. While FIG. 13 depicts a lower protrusion 1332, any protrusion, such as an upper protrusion or a protrusion extending across the thickness of the sample chamber, may be similarly constructed.
  • FIG. 14 is a cutaway side view depicting the top portion of a lower protrusion
  • the fluorescence reader 1512 detects the light emitted from the primers. Because regions 1550, 1552, 1554 are spatially isolated from one another (e.g., longitudinally offset along the length of the collection device 1502), each can fluoresce first, second, and third light 1556, 1558, 1560, respectively.
  • the fluorescence reader 1512 is thus able to distinctly identify the first light 1556 attributable to the region 1550 associated with Primer A, the second light 1558 attributable to the region 1552 associated with Primer B, and the third light 1560 attributable to the region 1554 associated with Primer C.
  • the fluorescence reader 1512 can include suitable sensors for distinguishing the presence and/or amount of light across its longitudinal length and thus is able to individually distinguish first light 1556, second light 1558, and third light 1560.
  • opaque (e.g., optically opaque) blockers can be used to limit the amount of light 1556 emitted from region 1550 from spilling into the portion of the fluorescence reader 1512 aligned with region 1552.
  • FIG. 16 is a flowchart depicting a process 1600 for collecting, amplifying, and analyzing a sample using an aerosolized sample collection device according to certain aspects of the present disclosure.
  • the collection device is prepared. Preparing the collection device can include removing seals from the inlet and outlet of the collection device. In some cases, preparing the collection device can include putting materials, such as DNA primers, PCA reagents, lysing materials, or other materials, into the collection device.
  • the aerosol sample is collected.
  • the aerosol sample can be collected by pressurizing an aerosol sample through the collection device, for example by exhaling into the collection device. In some cases, the aerosol sample can be collected by using negative pressure to draw an aerosol sample through the collection device.
  • the inlet and the outlet can be sealed.
  • the sample in the collection device is analyzed.
  • the sample can be analyzed by placing the collection device in an analysis machine, such as a machine including fluorescence sensors (e.g., optical sensors).
  • the collection device can be placed directly into the analysis machine.
  • the light can be emitted through an opening in the collection device, such as through a window.
  • the collection device can include a removable covering over the opening.
  • the removable covering can be removed to expose the sample chamber to the analysis machine.
  • FIG. 18 is a schematic diagram 1800 depicting an aerosolized collection device 1802 according to certain aspects of the present disclosure.
  • the aerosolized collection device 1802 can include an inlet 1804 and an outlet 1806 fluidly coupled within the collection device 1802 to allow passage of fluid through a cavity array 1808.
  • the cavity array 1808 can include multiple cavities 1810 having an internal surface area in fluid communication with the inlet 1804 and outlet 1806.
  • the internal surfaces of the cavities 1810 can be coated with or otherwise include surface particles designed to capture NA samples.
  • internal surfaces of the cavities 1810 can be coated with gold nanoparticles (AuNP). Coating the internal surfaces of the cavities 1810 can include depositing gold nanoparticles on the internal surfaces.
  • AuNP gold nanoparticles
  • a cavity array 1808 can include 72 cavities 1810, although any suitable number of cavities 1810 can be used.
  • Cavities 1810 can have various shapes and be fluidly coupled to the inlet 1804 and outlet 1806 in various configurations. In some cases, the cavities 1810 can be spherical in shape and connected together via passageways. In an example, as shown in cutout 1816, a cavity 1810 can include a generally spherical shape with an internal dome-shaped surface 1818. The dome-shaped surface can be generally shaped as a sphere segment or a spherical cap.
  • a pair of passageways 1820 can fluidly couple the cavity 1810 in a plane offset from the center of the cavity 1810. Cutout 1818 depicts front, side, and top views of the cavity 1810.
  • FIG. 19 is a schematic diagram depicting a process 1900 of collecting and amplifying NA samples using an aerosolized collection device according to certain aspects of the present disclosure.
  • NA samples 1904 can become captured in a cavity 1902 of the collection device in a capture phase.
  • thermal energy can be provided to the cavity 1902, such as through light 1906 emitted by a light source (e.g., one or more LEDs).
  • Thermal energy providing in the heating phase can denature NA samples 1904.
  • a cooling phase application of thermal energy can cease (e.g., by turning off the light source), allowing the NA samples 1904 in the cavity 1902 to undergo annealing and elongation (e.g., extension).
  • Heating and cooling phases can be repeated as necessary to achieve a desired amount of NA sample replication. In some cases, additional heating phases can be achieved by powering the light source under different duty cycles to provide desired amounts of thermal energy.
  • FIG. 20 is a schematic diagram 2000 depicting processing of NA samples using an aerosolized collection device 2002 and processing device 2004 according to certain aspects of the present disclosure.
  • the processing device 2004 can be a standalone device or a device couplable to a computing device 2006.
  • processing device 2004 can be a mobile processing device capable of coupling to a smartphone, tablet, or portable computer.
  • processing device 2004 can obtain power from and exchange data with the computing device 2006.
  • the processing device 2004 can contain necessary electronics, sensors, and outputs to perform one or more processing steps associated with the aerosolized collection device 2002.
  • the processing device 2004 can perform one or both of PCR and data collection (e.g., NA probe detection).
  • Processing device 2004 can include a light source or other thermal source for providing thermal energy to the collection device 2002.
  • Processing device 2004 can include one or more sensors for measuring or inferring a temperature of the collection device 2002 to provide control of PCR steps.
  • Processing device 2004 can include light sources suitable for fluorescing NA probes and/or sensors suitable for detecting NA probe fluorescence, such as light sensors or cameras.
  • the processing device 2004 can make use of sensors or energy sources of the computing device 2006.
  • a processing device 2004 can include apertures, mirrors, lenses, and/or light pipes to allow a camera or an energy source of the computing device 2006 to interact with the collection device 2002.
  • the set of diagrams 2100 depict velocity streamlines and particle tracings (e.g., after 0.25 seconds) within a cross section of the cavity 2102 at a centerline of the cavity 2102 for various dome 2104 (e.g., hump) heights ranging from 0 mm to 0.3 mm when an inlet fluid flow velocity is 2 m/s and at a cavity diameter of approximately 1 mm. It has been determined that dome 2104 heights of approximately 0.20 mm or 0.25 mm perform well, with high concentrations of capture particles. Other values of velocity, cavity 2102 size, and dome 2104 height can be used. As seen in the set of diagrams 2100, velocity profile and streamline are altered by a dome 2104.
  • dome 2104 e.g., hump
  • FIG. 23 is a set of charts 2300 depicting residence time statistics in the cavity
  • FIG. 24 is an axonometric diagram depicting flow 2402 through a long side of an array of cavities 2404 in an aerosolized collection device 2400 according to certain aspects of the present disclosure.
  • the array of cavities 2404 is depicted in cross section, showing domes 2406.
  • FIG. 25 is a top-view flow diagram depicting flow through the array of cavities 2404 of FIG. 24 according to certain aspects of the present disclosure. As seen in FIG. 25, high rates of fluid flow are seen over domes 2402 and passing between adjacent cavities. To facilitate interpreting the fluid flow diagram of FIGs. 25-38, regions of high flow rate are depicted by dark flow lines overlaid with dark arrows.
  • FIG. 26 is a flow diagram depicting the fluid flow through the array of cavities
  • FIG. 24 taken along a plane just beyond the height of the dome 2402 according to certain aspects of the present disclosure.
  • FIG. 28 is a flow diagram depicting the fluid flow through the array of cavities
  • FIG. 2404 of FIG. 24 taken along a plane intersecting the dome 2402 and intersecting more of the dome 2402 than the plane of FIG. 27 according to certain aspects of the present disclosure.
  • FIG. 29 is a flow diagram depicting the fluid flow through the array of cavities
  • FIG. 24 taken along a plane just beyond the height of the dome 2402 according to certain aspects of the present disclosure.
  • FIG. 30 is a flow diagram depicting the fluid flow through the array of cavities
  • FIG. 24 taken along a plane intersecting the dome 2402 according to certain aspects of the present disclosure.
  • FIG. 31 is a flow diagram depicting the fluid flow through the array of cavities
  • FIG. 32 is an axonometric diagram depicting flow 3202 through a long side of an array of cavities 3204 in an aerosolized collection device 3200 according to certain aspects of the present disclosure.
  • the array of cavities 3204 is depicted in cross section, showing domes 3206.
  • FIG. 33 is a top-view flow diagram depicting flow through the array of cavities 3204 of FIG. 32 according to certain aspects of the present disclosure. As seen in FIG. 33, high rates of fluid flow are seen over domes 3202 and passing between adjacent cavities. To facilitate interpreting the fluid flow diagram, regions of high flow rate are depicted by dark flow lines overlaid with dark arrows.
  • FIG. 35 is a flow diagram depicting the fluid flow through the array of cavities
  • regions of high flow rate are depicted by dark flow lines overlaid with dark arrows.
  • FIG. 36 is a flow diagram depicting the fluid flow through the array of cavities
  • FIG. 37 is a flow diagram depicting the fluid flow through the array of cavities
  • FIG. 38 is a flow diagram depicting the fluid flow through the array of cavities
  • FIG. 39 is a flow diagram depicting the fluid flow through the array of cavities
  • FIG. 40 is a set of illustrations 4000 depicting central fluid flow through a cylindrical chamber 4002 of an aerosolized collection device according to certain aspects of the present disclosure.
  • the cylindrical chamber 4002 can include an inlet passageway 4004 and an outlet passageway 4006 located at opposite faces of the cylindrical chamber 4002.
  • the inlet passageway 4004 and outlet passageway 4006 can both be aligned collinear with a center axis of the cylindrical chamber 4002.
  • the cylindrical chamber 4002 can have a diameter 4008.
  • the inlet passageway 4004 and outlet passageway 4006 can each have a diameter 4010, although they may have different diameters.
  • a single cylindrical chamber 4002 can include more than one inlet passageways 4004 and/or more than one outlet passageways 4006.
  • Central flow can include fluid flowing in the cylindrical chamber 4000 in a direction substantially parallel and/or collinear to the center axis of the cylindrical chamber 4000.
  • the set of illustrations 4000 further depict fluid flow patterns through the cylindrical chamber 4002 at various fluid flow velocities (Vin). More mixing and recirculation within the cylindrical chamber 4002 is seen at fluid flow velocities around 1 or 2 m/s.
  • FIG. 41 is a set of illustrations 4100 depicting cross fluid flow through a cylindrical chamber 4102 of an aerosolized collection device according to certain aspects of the present disclosure.
  • the cylindrical chamber 4102 can include an inlet passageway 4104 and an outlet passageway 4106 located at opposite faces of the cylindrical chamber 4102.
  • the inlet passageway 4104 and outlet passageway 4106 can be non-collinear with one another and non-collinear with a center axis of the cylindrical chamber 4102.
  • the inlet passageway 4104 and outlet passageway 4106 can be lie along imaginary lines located opposite the center axis of the cylindrical chamber 4102 from one another.
  • a single cylindrical chamber 4102 can include more than one inlet passageways 4104 and/or more than one outlet passageways 4106.
  • Cross fluid flow can include fluid flowing into and out of a central plane that is collinear with the center axis of the cylindrical chamber 4102.
  • the set of illustrations 4100 further depict fluid flow patterns through the cylindrical chamber 4102 at various fluid flow velocities (Vin).
  • FIG. 42 is a set of illustrations 4200 depicting offset fluid flow through a cylindrical chamber 4202 of an aerosolized collection device according to certain aspects of the present disclosure.
  • the cylindrical chamber 4202 can include an inlet passageway 4204 and an outlet passageway 4206 located at opposite faces of the cylindrical chamber 4202.
  • the inlet passageway 4204 and outlet passageway 4206 can be collinear with one another and non-collinear with a center axis of the cylindrical chamber 4202.
  • the shared axis of the inlet passageway 4204 and outlet passageway 4206 can be parallel to and offset from the center axis of the cylindrical chamber 4202.
  • a single cylindrical chamber 4202 can include more than one inlet passageways 4204 and/or more than one outlet passageways 4206.
  • Offset fluid flow can include fluid flowing in a direction substantially parallel to, but offset from, the center axis of the cylindrical chamber 4202.
  • the set of illustrations 4200 further depict fluid flow patterns through the cylindrical chamber 4202 at various fluid flow velocities (Vin).
  • FIG. 43 is a set of illustrations 4300 depicting central fluid flow through a spherical chamber 4302 of an aerosolized collection device according to certain aspects of the present disclosure.
  • the spherical chamber 4302 can include an inlet passageway 4304 and an outlet passageway 4306 located at opposite ends of the spherical chamber 4302.
  • the inlet passageway 4304 and outlet passageway 4306 can both be aligned collinear with a center axis between the ends of the spherical chamber 4302.
  • the spherical chamber 4302 can have a diameter 4308.
  • the inlet passageway 4304 and outlet passageway 4306 can each have a diameter 4310, although they may have different diameters.
  • a single spherical chamber 4302 can include more than one inlet passageways 4304 and/or more than one outlet passageways 4306.
  • Central flow can include fluid flowing in the spherical chamber 4300 in a direction substantially parallel and/or collinear to the center axis of the spherical chamber 4300.
  • the set of illustrations 4300 further depict fluid flow patterns through the spherical chamber 4302 at various fluid flow velocities (V m ). More mixing and recirculation within the spherical chamber 4302 is seen at fluid flow velocities around 1 or 2 m/s.
  • FIG. 44 is a set of illustrations 4400 depicting cross fluid flow through a spherical chamber 4402 of an aerosolized collection device according to certain aspects of the present disclosure.
  • the spherical chamber 4402 can include an inlet passageway 4404 and an outlet passageway 4406 located at opposite ends of the spherical chamber 4402.
  • the inlet passageway 4404 and outlet passageway 4406 can be non-collinear with one another and non-collinear with a center axis between the ends of the spherical chamber 4402.
  • the inlet passageway 4404 and outlet passageway 4406 can be lie along imaginary lines located opposite the center axis of the spherical chamber 4402 from one another.
  • FIG. 45 is a set of illustrations 4500 depicting offset fluid flow through a spherical chamber 4502 of an aerosolized collection device according to certain aspects of the present disclosure.
  • the spherical chamber 4502 can include an inlet passageway 4504 and an outlet passageway 4506 located at opposite ends of the spherical chamber 4502.
  • the inlet passageway 4504 and outlet passageway 4506 can be collinear with one another and non- collinear with a center axis between the ends of the spherical chamber 4502.
  • the shared axis of the inlet passageway 4504 and outlet passageway 4506 can be parallel to and offset from the center axis of the spherical chamber 4502.
  • a single spherical chamber 4502 can include more than one inlet passageways 4504 and/or more than one outlet passageways 4506. Offset fluid flow can include fluid flowing in a direction substantially parallel to, but offset from, the center axis of the spherical chamber 4502.
  • FIG. 46 is an axonometric flow diagram 4600 depicting fluid flow through a series of closely offset spherical chambers 4602 of an aerosolized collection device according to certain aspects of the present disclosure.
  • the spherical chambers 4602 can be arranged serially, such that an outlet passageway of one spherical chamber 4602 is the inlet passageway of a subsequent spherical chamber 4602.
  • a collection device can include one or more collections of serial chambers fluidly coupling the inlet of the collection device with the outlet of the collection device.
  • FIG. 47 is a cross-sectional flow diagram 4700 depicting fluid flow through the series of closely offset spherical chambers 4602 of FIG. 46 according to certain aspects of the present disclosure.
  • the chambers 4602 can be arranged to produce a dimensionless residence time that is at or approximately 202.61.
  • FIG. 48 is an axonometric flow diagram 4800 depicting fluid flow through a series of offset spherical chambers 4802 of an aerosolized collection device according to certain aspects of the present disclosure.
  • the spherical chambers 4802 can be arranged serially, such that an outlet passageway of one spherical chamber 4802 is the inlet passageway of a subsequent spherical chamber 4802.
  • a collection device can include one or more collections of serial chambers fluidly coupling the inlet of the collection device with the outlet of the collection device.
  • FIG. 50 is an axonometric flow diagram depicting fluid flow through a series of parallel-offset spherical chambers 5002 of an aerosolized collection device according to certain aspects of the present disclosure.
  • the parallel-offset spherical chambers 5002 can be arranged in parallel groups, each group serially arranged with subsequent groups. Multiple (e.g., two) spherical chambers 5002 of a parallel group can share a single inlet passageway. One or more outlet passageways of a parallel group can then feed into the inlet passageway of a subsequent parallel group.
  • a collection device can include one or more collections of serial parallel groups of chambers fluidly coupling the inlet of the collection device with the outlet of the collection device.
  • FIG. 51 is a cross-sectional flow diagram 5100 depicting fluid flow through the series of parallel-offset spherical chambers 5002 of FIG. 50 according to certain aspects of the present disclosure.
  • the chambers 5002 can be arranged to produce a dimensionless residence time that is at or approximately 209.13. Comparison of FIGs. 47 and 51 show that a higher dimensionless residence time can be achieved by arranging the chambers in parallel groups.
  • FIG. 52 is a schematic view and close-up view of a serialized array of chambers 5200 of an aerosolized collection device according to certain aspects of the present disclosure.
  • the array 5200 can include one or more serial paths 5202, each path 5202 containing a set of chambers 5204 (e.g., spherical chambers) arranged in serial between the inlet and outlet of the aerosolized collection device.
  • a set of chambers 5204 e.g., spherical chambers
  • FIG. 53 is a schematic view and close-up view of an interconnected array of chambers 5300 of an aerosolized collection device according to certain aspects of the present disclosure.
  • the array 5300 can include multiple chambers 5204 arranged between the inlet and outlet of the aerosolized collection device.
  • the array 5300 may be interconnected because some or all chambers 5204 are interconnected with neighboring chambers 5204 serially and in parallel.
  • FIG. 54 is an axonometric diagram depicting a clamshell-style aerosolized collection device 5400 according to certain aspects of the present disclosure.
  • the collection device 5400 can include features formed into a top body 5404 and a bottom body 5406 such that chambers 5402 are formed when the top body 5404 is placed against the bottom body 5406.
  • FIG. 56 is a see-through, side view depicting the clamshell aerosolized collection device 5400 of FIG. 54 according to certain aspects of the present disclosure.
  • the height of the collection device 5400 is shown as being 2 mm.
  • the diameter of each chamber 5402 is shown as being 1 mm.
  • the width of the inlet portion is shown as being 10 mm. Other sizes may be used.
  • FIG. 57 is a sectional side view of an aerosolized collection device 5700 according to certain aspects of the present disclosure.
  • the aerosolized collection device 5700 includes multiple chambers 5702 formed between a top body portion 5704 and a bottom body portion 5706.
  • the top body portion 5704 and bottom body portion 5706 can be of unibody construction or made of multiple parts.
  • the aerosolized collection device 5700 can be shaped to be mirrored across one or more axes of the aerosolized collection device 5700 such that the aerosolized collection device 5700 can be inserted into a processing device in any multiple different direction (e.g., in a first direction or in a second direction opposite the first direction).
  • Fluid dynamic simulations were performed on various styles of collection devices, such as those described herein with reference to the various figures.
  • t and ⁇ are time and its dimensionless form. ⁇ is normalized by ⁇ (V/Q; volume and volume flow rate). Cm and C ou t are the particle concentration at inlet and outlet, respectively. [0165] Under ideal conditions, all molecules may spend the same amount of time in the channel. However, the actual residence time may be varied where recirculation of flow exists. In such cases, the variance of the residence time will be greater since the molecules will spend different time in the channel. Results of at least some of these simulations are depicted with reference to FIG. 23.
  • any reference to a series of examples is to be understood as a reference to each of those examples disjunctively (e.g., "Examples 1-4" is to be understood as “Examples 1, 2, 3, or 4").
  • Example 1 is a sample collection device comprising a sample chamber including an inlet for accepting an aerosol sample and an outlet; an array of protrusions extending from one or more walls of the sample chamber; and a window located in a wall of the sample chamber for exposing the sample chamber to an exterior of the device.
  • Example 2 is the device of example 1, wherein the one or more walls of the sample chamber are made of plasmonic materials coated with a protective layer.
  • Example 3 is the device of example 2, wherein the protective layer is made of
  • Example 6 is the device of examples 1-5, further comprising PCR reagents preloaded into the sample chamber.
  • Example 7 is the device of examples 1-6, further comprising a plurality of
  • DNA primers wherein the plurality of DNA primers comprises a first primer preloaded into a first region of the sample chamber and a second primer preloaded into a second region of the sample chamber.
  • Example 8 is a method, comprising passing an aerosolized sample through a sample chamber of a collection device, wherein passing the aerosolized sample through the sample chamber includes depositing genetic material on internal surfaces of the sample chamber; placing the collection device in a polymerase chain reaction (PCR) machine; thermal cycling the collection device in the PCR machine; and measuring emitted radiation from the collection device.
  • PCR polymerase chain reaction
  • Example 9 is the method of example 8, wherein the internal surfaces of the sample chamber of the collection device include plasmonic materials coated with a protective layer.
  • Example 10 is the method of example 9, wherein the protective layer is made of Si02 or A1203.
  • Example 11 is the method of examples 8-10, wherein the sample chamber of the collection device comprises a set of upper protrusions extending from a top wall of the sample chamber and a set of lower protrusions extending from a bottom wall of the sample chamber, and wherein each protrusion of the set of upper protrusions and the set of lower protrusions has a height at least half as tall as a thickness of the sample chamber.
  • Example 12 is the method of examples 8-11, wherein passing the aerosolized sample through the sample chamber includes inducing a standing wave within the sample chamber, and wherein the internal surfaces of the sample chamber are arranged to facilitate formation of the standing wave within the sample chamber.
  • Example 13 is the method of examples 8-12, further comprising preloading the sample chamber with PCR reagents.
  • Example 14 is the method of examples 8-13, further comprising preloading the sample chamber with a plurality of DNA primers, wherein preloading the sample chamber with the DNA primers includes preloading a first primer into a first region of the sample chamber and preloading a second primer into a second region of the sample chamber.
  • Example 16 is the system of example 15, wherein the one or more walls of the sample chamber are made of plasmonic materials coated with a protective layer.
  • Example 17 is the system of example 16, wherein the protective layer is made of Si02 or A1203.
  • Example 18 is the system of examples 15-17, wherein the array of protrusions comprises a set of upper protrusions extending from a top wall of the sample chamber and a set of lower protrusions extending from a bottom wall of the sample chamber, and wherein each protrusion of the set of upper protrusions and the set of lower protrusions has a height at least half as tall as a thickness of the sample chamber.
  • Example 20 is the system of examples 15-19, wherein the collection device further comprises PCR reagents preloaded into the sample chamber.

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Abstract

L'invention concerne un dispositif de collecte, d'amplification et d'analyse d'un échantillon en aérosol contenant un matériel génétique. Des saillies internes créent une grande surface permettant de capturer un matériel génétique à partir de l'échantillon en aérosol passant à travers une chambre d'échantillon interne du dispositif. L'ensemble du dispositif peut ensuite être placé dans un thermocycleur pour procéder à une amplification de réaction en chaîne de la polymérase sans qu'il soit nécessaire de retirer l'échantillon. Des amorces et/ou d'autres matériaux peuvent être inclus dans le dispositif ou ajoutés après la collecte d'échantillons. Après l'amplification, l'ensemble du dispositif peut être analysé sans retirer le matériel génétique amplifié du dispositif, par exemple par fluorescence mesurée. Le dispositif, comprenant les saillies internes, peut être constitué de ou comprendre une couche plasmonique protégée par un revêtement de film mince (par exemple, SiO2 ou Al2O3), ce qui peut aider à éviter une extinction fluorescente pendant l'analyse. L'ensemble du dispositif peut analyser rapidement, facilement, efficacement et de manière jetable un matériel génétique dans un échantillon en aérosol.
PCT/US2017/068929 2016-12-30 2017-12-29 Dispositif de capture et de traitement d'aérosol WO2018126119A1 (fr)

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GB2595572A (en) * 2020-04-15 2021-12-01 Vosbio Inc Methods, devices and kits for preparing nucleic acid samples for storage and analysis
WO2022228967A1 (fr) * 2021-04-26 2022-11-03 Imec Vzw Dispositif de collecte et procédé de collecte de particules en suspension dans l'air expirées par un être humain
EP4265180A1 (fr) * 2022-04-20 2023-10-25 miDiagnostics NV Dispositif d'échantillonnage et d'analyse intégré

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