WO2022098878A1 - Méthode, dispositif et kit de collecte et de traitement d'un échantillon biologique - Google Patents

Méthode, dispositif et kit de collecte et de traitement d'un échantillon biologique Download PDF

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Publication number
WO2022098878A1
WO2022098878A1 PCT/US2021/058070 US2021058070W WO2022098878A1 WO 2022098878 A1 WO2022098878 A1 WO 2022098878A1 US 2021058070 W US2021058070 W US 2021058070W WO 2022098878 A1 WO2022098878 A1 WO 2022098878A1
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WO
WIPO (PCT)
Prior art keywords
container
barrier
sample
opening
hollow interior
Prior art date
Application number
PCT/US2021/058070
Other languages
English (en)
Inventor
Aftab Alam
Original Assignee
Aftab Alam
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 Aftab Alam filed Critical Aftab Alam
Publication of WO2022098878A1 publication Critical patent/WO2022098878A1/fr

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Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/16—Reagents, handling or storing thereof
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/04—Closures and closing means
    • B01L2300/041—Connecting closures to device or container
    • B01L2300/042—Caps; Plugs
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0832—Geometry, shape and general structure cylindrical, tube shaped
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/12—Specific details about materials
    • B01L2300/126—Paper
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/06—Valves, specific forms thereof
    • B01L2400/0633—Valves, specific forms thereof with moving parts
    • B01L2400/0644—Valves, specific forms thereof with moving parts rotary valves
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/90—Enzymes; Proenzymes
    • G01N2333/914—Hydrolases (3)
    • G01N2333/948—Hydrolases (3) acting on peptide bonds (3.4)
    • G01N2333/95—Proteinases, i.e. endopeptidases (3.4.21-3.4.99)
    • G01N2333/964—Proteinases, i.e. endopeptidases (3.4.21-3.4.99) derived from animal tissue
    • G01N2333/96425—Proteinases, i.e. endopeptidases (3.4.21-3.4.99) derived from animal tissue from mammals
    • G01N2333/96427—Proteinases, i.e. endopeptidases (3.4.21-3.4.99) derived from animal tissue from mammals in general
    • G01N2333/9643—Proteinases, i.e. endopeptidases (3.4.21-3.4.99) derived from animal tissue from mammals in general with EC number
    • G01N2333/96433—Serine endopeptidases (3.4.21)
    • G01N2333/96441—Serine endopeptidases (3.4.21) with definite EC number

Definitions

  • the present disclosure relates to collecting and processing a biological sample, and more particularly, to a method, device, and kit for collecting and processing a biological sample.
  • Biological samples are collected from donors and tested to determine whether the samples contain harmful viruses or bacteria, or whether the samples have physical characteristics that fall within a normal range for the donor type or fall outside that range. These samples may include bodily fluids such as saliva or sputum, and may contain liquid, gaseous, and solid materials.
  • Some prior sample collection containers have had an opening permitting a sample to be collected in an interior of the container.
  • these containers include a screw lid for selectively blocking the opening.
  • foreign substances are unlikely to be introduced into the interior of the container prior to opening the container for collecting the sample.
  • these containers include a paper label affixed to both the container and lid, indicating the container has not been opened when the label is intact.
  • the label tears, indicating the container has been opened prior to use and foreign substances could have been introduced into the container that could potentially invalidate subsequent tests.
  • the lid can be reattached to the container to prevent the sample from being contaminated with foreign substances before being opened to process the sample.
  • the lid When reattached to the container, the lid prevents samples from escaping from the container during subsequent handling and processing. This feature is particularly important when the sample might be infectious. Often, samples are not tested where they are collected. Rather, the samples are transported to labs in other facilities for testing. Depending upon numerous factors, the samples may be degraded or deteriorate during transport to the labs, particularly when transportation or storage occurs over extended periods.
  • the disclosure includes a device for collecting and processing a biological sample.
  • the device comprises a container having a hollow interior extending between an opening and an end wall opposite the opening.
  • the device also includes a closure selectively attachable to the container to prevent passage through the opening and a barrier mounted in the hollow interior of the container at a position spaced from the end wall to provide a retention chamber between the barrier and the end wall.
  • a sample processing reagent is provided in the retention chamber.
  • the disclosure includes a method of processing a biological sample in a container having a hollow interior extending between an opening and an end wall opposite the opening, a barrier mounted in the hollow interior of the container at a position spaced from the end wall to provide a retention chamber between the barrier and the end wall, and a sample processing reagent positioned for contacting the sample in the retention chamber.
  • the method comprises depositing a biological sample through the opening into the hollow interior of the container and allowing the biological sample to pass the barrier and contact the sample processing reagent in the retention chamber.
  • the disclosure includes a kit for collecting and processing of a biological sample.
  • the kit comprises a device including a container having a hollow interior extending between an opening and an end wall opposite the opening, a closure selectively attachable to the container to prevent passage through the opening, a barrier mounted in the hollow interior of the container at a position spaced from the end wall to provide a retention chamber between the barrier and the end wall, and a sample processing reagent provided in the retention chamber.
  • the kit includes a collection receiver having a passage extending between a narrower end sized for mounting in the opening of the container and a wider end opposite the narrower end having a width larger than the opening to facilitate depositing the biological sample in the hollow interior of the container.
  • FIG. 1 is a schematic cross-sectional elevation of a first illustrated example of a device for collecting a biological sample such as saliva!
  • FIG. 2 is a front elevation of a tool for changing barrier orientation in the device shown in FIG. 1!
  • FIG. 3a is a schematic cross-sectional elevation of the device shown in FIG. 1 after a biological sample is collected;
  • FIG. 3b is a schematic cross-sectional elevation of the device shown in FIG. 3a having its barrier pivoted by the tool shown in FIG. 2 to allow the collected biological sample to enter a chamber of the device!
  • FIG. 3c is a schematic cross-sectional elevation of the device shown in FIG. 3b having a closure attached thereto!
  • FIG. 3d is a schematic cross-sectional elevation of the device shown in FIG. 3c after a stopper has been removed from its outlet allowing the sample to drain from the outlet!
  • FIG. 4 is a schematic perspective of a second illustrated example of a device for collecting a biological sample such as saliva!
  • FIG. 5 is a schematic perspective of a receiver for selective use in combination with the device shown in FIG. 4 to facilitate collecting a biological sample!
  • FIG. 6 is a schematic perspective of a barrier of the device of FIG. 4.
  • the device 10 includes a generally cylindrical container, generally designated by 12, having a hollow interior 14 extending between an opening 16 and an end wall 18 opposite the opening.
  • a tubular nozzle or outlet 20 extends through the end wall 18, permitting fluid to be selectively withdrawn from the hollow interior 14 of the container 12.
  • the outlet 20 may have other configurations, the outlet of the illustrated device 10 has a twist-to-break stopper 22 fused to the outlet during manufacture as shown in FIG. 1.
  • the stopper 22 is frangibly attached to the outlet 20 so the stopper breaks free and separates from the outlet when twisted to allow sample to drain through the outlet.
  • the stopper and outlet may have an interlocking annular groove and ridge instead of the twist-to-break stopper.
  • the stopper and outlet are press fit.
  • the container 12 includes a conical receiver 30 adjacent the opening 16.
  • the receiver 30 provides a larger inner diameter at the opening 16 to facilitate fluid being introduced into the hollow interior 14 of the container 12 without spilling.
  • the opening 16 has a fastener element 32, e.g., a screw thread, to selectively fasten a cap or closure, generally designated by 40, to the container 12 to prevent dust or other foreign material from entering the hollow interior 14 through the opening 16 prior to collecting a sample and to prevent the sample from unintentionally escaping the hollow interior after collection.
  • the closure 40 has a fastener element 42 corresponding to the fastener element 32 on the container 12 to selectively fasten the closure to the container.
  • a barrier or gate 50 is mounted in the hollow interior 14 at a position spaced from the end wall 18 to provide a retention chamber 52 between the barrier and end wall.
  • the barrier illustrated in FIG. 1 comprises a porous frit.
  • the illustrated frit is a disk sized to be press fit into the hollow interior 14 of the container 12.
  • the frit may be treated or impregnated with a sample processing chemical and/or a reagent.
  • reagents may be placed and stored in the chamber 52 between the barrier 50 and end wall 18.
  • a solid matrix 54 (broadly, a support), e.g., a paper disk, carrying a processing reagent is held in the chamber 52.
  • FIG. 2 shows an elongated tool 60 for moving the barrier 50.
  • the device 10 may be assembled as shown in FIG. 1 for transport to a donor.
  • the donor will remove the closure 40 from the container 12 and deposit a sample S in the container through the opening 16.
  • a donor will deposit saliva directly into the hollow interior 14 of the container 12.
  • a tool 60 will be inserted through the opening 16 to engage a margin of the barrier 50 to pivot the barrier about a diametric axis to a position as shown in FIG. 3b in which the sample S flows into the chamber 52 and contacts the matrix 54 held in the chamber.
  • FIG. 3b shows an elongated tool 60 for moving the barrier 50.
  • the tool 60 is sized to permit the closure 40 to be attached to the container 12 while the tool is in the hollow interior 14 of the container to ensure the barrier 50 is held in its pivoted or open position.
  • the device 10 may be held at a desired temperature for a period selected to permit a chemical reaction between the sample S and reactants on the matrix 54.
  • the stopper 22 is removed from the outlet 20 as shown in FIG. 3d to allow the sample to flow through the outlet for further processing.
  • the sample S may be withdrawn through the opening 16. It is envisioned that once the sample is removed, the device as shown in FIG. 3d may be disposed of in a conventional suitable manner.
  • a second illustrated example of a device for collecting and processing a biological sample is designated in its entirety by the reference number 110 in FIG. 4.
  • the device 110 includes a cylindrical container, generally designated by 112, having a hollow interior 114 extending between an opening 116 and an end wall, generally designated by 118, opposite the opening.
  • the end wall 118 of the second illustrated example does not have a flow outlet.
  • the end wall 118 has an outward facing convex face 124 and an annular rim 126 surrounding the end wall to permit the device 110 to be balanced on the rim.
  • the end wall 119 may be planar and the rim 126 may be omitted.
  • the device 100 of the second example shown in FIG. 4 are used in combination with a selectively detachable collection receiver or funnel, generally designated by 134, as shown in FIG. 5, rather than having an integrated conical receiver 30.
  • the collection receiver 134 has a narrower end 136 configured to mount on or be inserted into the opening 116 of the container 112 of the second example.
  • the receiver 134 includes a wider end 138 opposite the narrower end 136 to facilitate fluid being introduced into the hollow interior 114 of the container 112 without spilling. Once, the sample is collected, the receiver 134 may be removed from the container 112 and disposed of in a conventional manner.
  • the opening 116 has a fastener element 132, e.g., a screw thread, to selectively fasten a cap or closure, generally designated by 140, to the container 112 to prevent foreign substances from entering the hollow interior 114 through the opening 116 prior to collecting a sample and to prevent the sample from unintentionally escaping the hollow interior after collection.
  • the closure 140 has a fastener element (not shown) corresponding to the fastener element 132 on the container 112 to selectively fasten the closure to the container.
  • a barrier or gate is mounted in the hollow interior 114 at a position spaced from the end wall 118 creating a retention chamber 152 between the barrier and end wall.
  • the barrier illustrated in FIGS. 4 and 6 comprises a disk sized to be press fit into the hollow interior 114 of the container 112.
  • the barrier 156 includes a plurality of orifices 158 permitting fluid to pass through the barrier.
  • the barrier 156 need not be pivoted to allow the sample to enter the chamber 152.
  • the orifices 158 also permit a tool (not shown) to pass through and/or engage the barrier 156 to remove the barrier from the hollow interior 114 should a need arise.
  • a solid matrix 154 (e.g., a paper disk) carrying a processing reagent is held in the chamber 152.
  • the orifices 158 are sized to prevent larger solids from passing through the barrier 150 to the chamber 152 and to prevent the matrix 154 from escaping the chamber.
  • a conventional pipette (not shown) may be used to withdraw a sample from the chamber 152.
  • the container 112 may be inverted to allow the sample to drain out of the chamber 152 and through the opening 116.
  • the components of the first and second devices 10, 110 may be manufactured from suitable materials, such as appropriate polymers using conventional manufacturing processes.
  • Reagents used for processing saliva samples are as follows. An appropriate quantity of one or more agents is applied to paper disks or a frit and dried.
  • Reagent-A 2.5% Tween-20 detergent, containing 100 pM (2-carboxyethyl) phosphine hydrochloride (TCEP HC1) reducing agent and 100 pM Ethylenediaminetetraacetic acid (EDTA), buffered with 10 mM tris(hydroxymethyl)aminomethane (Tris) pH 7.5. In some cases, 100 pl of Reagent-A was loaded into the chamber (e.g., chamber 52 or 152) of the device.
  • TCEP HC1 2-carboxyethyl) phosphine hydrochloride
  • EDTA Ethylenediaminetetraacetic acid
  • Tris tris(hydroxymethyl)aminomethane
  • Reagent-B (Proteinase -K): 1 mg per dose per device was impregnated on a paper disk or a frit or prepared in dry form as reagent balls or pellets.
  • Reagent-B Proteinase-K also contains 1 mM calcium chloride in 10 mM Tris buffer pH 7.0.
  • Reagent'C 100 mM TCEP is provided on a paper disk or a frit or prepared in dry form. In some cases, 25 to 50 pl per dose per device is loaded into the chamber of the device.
  • Example 1 a device such as described above may contain Reagent-A, Reagent-B, or Reagent-C or a blend or combination of Reagent-A, Reagent-B, and/or Reagent-C may be used.
  • the Reagent-A, Reagent-B, or Reagent-C provided either individually or in dry combination will be stable for storage as frozen, or at a cold temperature of 4° to 10° Celsius or at room temperature and/or at an ambient temperature of 20° to 40° Celsius for an extended period beyond one to six months and in some cases up to twelve months or longer.
  • Proteinase-K when provided as dry form, immobilized, or impregnated in a dry solid matrix or paper disk, reagent balls, pellets, or a dry support matrix is stable for extended periods, extending storage shelf life for months, or up to a year or longer at ambient temperature in some cases.
  • Reagent-B Proteinase-K
  • Reagent-B in dry form, impregnated in solid matter, a paper disk or a solid matrix, is deposited inside the chamber of a device.
  • Proteinase-K may also be provided as impregnated and/or immobilized in some form of solid absorbing materials such as a paper disk and/or a frit, a polymer porous frit, balls, or pellets.
  • Reagent-A and Reagent-C as dry form, impregnated in solid matter or a matrix, immobilized in solid matter, is deposited inside the chamber of a device.
  • Reagent-A and Reagent-C is provided as impregnated in some form of solid absorbing materials, such as a paper disk and/or a frit, or a polymer frit.
  • the barrier comprises a frit impregnated with one or more of Reagent-A, Reagent-B, or Reagent-C and the impregnated frit is positioned inside the chamber.
  • the barrier must be pivoted to mix the sample with the processing reagents in the chamber.
  • the sample When a device such as that described above with respect to FIG. 4 where the container has a barrier with apertures, the sample will migrate through the apertures past the barrier and mix with the processing reagents in the chamber, without requiring a barrier moving device or moving the barrier.
  • the processing reagent is provided on a solid matrix, such as paper disk, or as reagent pellets or balls.
  • the restrictive apertures are sized to prevent the processing reagent impregnated solid matrix, paper disks, pellets, or balls from migrating out of the chamber past the barrier.
  • the processing reagent is encapsulated in the barrier.
  • the tool is used to release the reagent, allowing the sample and reagent to mix as they pass through the barrier to the chamber.
  • the processing reagent is dried on the barrier, e.g., as a frit impregnated with processing reagent. In these cases, reagent mixes with the sample as the sample passes over the frit and into the chamber.
  • the processing Reagent-A, Reagent-B, or Reagent'C will act on the saliva sample when they make contact.
  • a short incubation period may be allowed for completion of the reaction process.
  • Transportation or transit time may be used as incubation period in some cases. Incubation is performed, either at ambient temperature or at an elevated temperature, e.g., between 30° and 60° Celsius - or at both, i.e., ambient treatment followed by elevated temperature treatment.
  • the device is placed and heated in boiling water or on heat block, at temperature around or higher than 90° Celsius for 1 to 15 minutes depending on the nature of the processing.
  • the processed sample is removed for downstream processing.
  • the closed end flow outlet will be opened by twisting the stopper to separate the stopper and the sample will be collected for further processing.
  • the stopper may also be broken by snapping it at an angle.
  • the outlet of the container may be placed inside a narrow collection tube, and the closure separated using the tube as a lever to snap the stopper an angle.
  • Processed samples may also be retrieved by reaching inside the hollow interior from the opening of the container.
  • the processed samples will be retrieved by reaching inside the hollow interior through the opening of the container.
  • the processed samples will be retrieved using a retrieval tool such as pipette tips passing through the apertures of the barrier.
  • the barrier is prepared by soaking or impregnating a frit with Reagent-A and drying. In some cases 100 pl of Reagent-A is used per frit per device.
  • a paper disk is absorbed and impregnated with Reagent-B, either air-dried or lyophilized. Both samples of Reagent-B, with and without a calcium salt, are tested.
  • Test 1 a device as described above is provided with a barrier frit containing Reagent-A, 100 pl per frit per device.
  • Test 2- a device as described above is provided with Reagent-B on paper disks in the chamber. In this test, 1 mg Proteinase-K per dose per device is used.
  • Test 3 a device as described above is provided with a barrier frit containing Reagent-A and/or Reagent-B in the chamber.
  • Test 4 a device as described above is provided with Reagent-B on paper disk in the chamber with the Proteinase-K containing calcium chloride in the reagent with buffering agent.
  • Test 5- a device as described above is provided with Reagent-C in the chamber and/or barrier. In this test, 25 to 50 pl per dose per device is used.
  • Saliva samples are collected and treated as described above in the five tests. After collection of samples, the barrier was pivoted open with the tool. In the case of the device where the barrier has apertures, the sample freely migrates through the apertures into the chamber and contacts the processing reagent provided there in solid matrix.
  • test 5 is not heated above ambient.
  • processed samples were collected for downstream processing. In some cases, 5 pl of processed samples were analyzed by RT-PCR and RT-LAMP for Covid- 19 marker amplification. In these tests, all four tests provided positive amplification. The test 5 sample was successfully analyzed for both COVID antigens and antibodies.
  • Reagent-B as described above in Example 1 was stored for twelve months at an ambient temperature of 37° to 40° Celsius.
  • the activity of Proteinase-K was measured against a control stored frozen at -20° C. After twelve months, the Proteinase-K impregnated on paper disk was found to be substantially active to perform the function of protein digestion.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Analytical Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Hematology (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Investigating Or Analysing Biological Materials (AREA)

Abstract

Dispositif de collecte et de traitement d'un échantillon biologique, comprenant un récipient présentant un intérieur creux s'étendant entre une ouverture et une paroi d'extrémité opposée à l'ouverture. Le dispositif comprend une fermeture pouvant être fixée de manière sélective au récipient permettant d'empêcher un passage à travers l'ouverture et une barrière montée dans l'intérieur creux du récipient à une position espacée de la paroi d'extrémité permettant de fournir une chambre de rétention entre la barrière et la paroi d'extrémité. Un réactif de traitement d'échantillon est fourni dans la chambre de rétention. Une méthode de traitement d'un échantillon biologique dans un dispositif consiste à déposer un échantillon biologique à travers l'ouverture dans l'intérieur creux du récipient et à permettre à l'échantillon biologique de passer la barrière et de venir en contact avec le réactif de traitement d'échantillon dans la chambre de rétention. Un kit comprenant un dispositif de collecte et de traitement d'échantillon biologique et un récepteur doté d'un passage s'étendent entre des extrémités plus étroite et plus large.
PCT/US2021/058070 2020-11-06 2021-11-04 Méthode, dispositif et kit de collecte et de traitement d'un échantillon biologique WO2022098878A1 (fr)

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
US202063198721P 2020-11-06 2020-11-06
US63/198,721 2020-11-06
US202063199239P 2020-12-15 2020-12-15
US63/199,239 2020-12-15
US202063199428P 2020-12-27 2020-12-27
US63/199,428 2020-12-27

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Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US474134A (en) * 1892-05-03 John n
US4055501A (en) * 1976-01-16 1977-10-25 Sherwood Medical Industries Inc. Fluid collection device with phase partitioning means
US5738670A (en) * 1995-02-21 1998-04-14 Becton, Dickinson And Company Blood collection assembly having additive dispensing means
US6251660B1 (en) * 1997-11-25 2001-06-26 Mosaic Technologies, Inc. Devices and methods for detecting target molecules in biological samples
WO2011041703A2 (fr) * 2009-10-02 2011-04-07 Life Technologies Corporation Dispositifs et procédés de préparation d'échantillons
US20170023451A1 (en) * 2011-12-31 2017-01-26 Telomere Diagnostics, Inc. Saliva-Derived Measures of Telomere Abundance and Sample Collection Device

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US474134A (en) * 1892-05-03 John n
US4055501A (en) * 1976-01-16 1977-10-25 Sherwood Medical Industries Inc. Fluid collection device with phase partitioning means
US5738670A (en) * 1995-02-21 1998-04-14 Becton, Dickinson And Company Blood collection assembly having additive dispensing means
US6251660B1 (en) * 1997-11-25 2001-06-26 Mosaic Technologies, Inc. Devices and methods for detecting target molecules in biological samples
WO2011041703A2 (fr) * 2009-10-02 2011-04-07 Life Technologies Corporation Dispositifs et procédés de préparation d'échantillons
US20170023451A1 (en) * 2011-12-31 2017-01-26 Telomere Diagnostics, Inc. Saliva-Derived Measures of Telomere Abundance and Sample Collection Device

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