WO1997012681A1 - Dispositif pour collecter, recuperer et distribuer des echantillons de salive - Google Patents

Dispositif pour collecter, recuperer et distribuer des echantillons de salive Download PDF

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Publication number
WO1997012681A1
WO1997012681A1 PCT/US1996/016075 US9616075W WO9712681A1 WO 1997012681 A1 WO1997012681 A1 WO 1997012681A1 US 9616075 W US9616075 W US 9616075W WO 9712681 A1 WO9712681 A1 WO 9712681A1
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WO
WIPO (PCT)
Prior art keywords
sample
improvement
closure
container
fluid
Prior art date
Application number
PCT/US1996/016075
Other languages
English (en)
Inventor
Henry B. Schur
Jack L. Aronowitz
Nicholas G. Levandoski
Joel R. Mitchen
Original Assignee
Analyte Diagnostics, Inc.
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 Analyte Diagnostics, Inc. filed Critical Analyte Diagnostics, Inc.
Priority to AU73946/96A priority Critical patent/AU7394696A/en
Publication of WO1997012681A1 publication Critical patent/WO1997012681A1/fr
Priority to PCT/US1997/012880 priority patent/WO1998014276A1/fr
Priority to AU39623/97A priority patent/AU3962397A/en

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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
    • B01L3/508—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above
    • B01L3/5082—Test tubes per se
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B10/00—Other methods or instruments for diagnosis, e.g. instruments for taking a cell sample, for biopsy, for vaccination diagnosis; Sex determination; Ovulation-period determination; Throat striking implements
    • A61B10/0045—Devices for taking samples of body liquids
    • A61B10/0051—Devices for taking samples of body liquids for taking saliva or sputum samples
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B10/00—Other methods or instruments for diagnosis, e.g. instruments for taking a cell sample, for biopsy, for vaccination diagnosis; Sex determination; Ovulation-period determination; Throat striking implements
    • A61B2010/0009—Testing for drug or alcohol abuse

Definitions

  • This invention is directed to a device for the collection, recovery and dispensing of a fluid sample, including biological fluid, such as saliva. More specifically, the instant invention is directed to a simple, yet effective device for collecting, recovery and dispensing of a fluid sample for on-the-spot testing and, optionally, for sample transport and/or archival retention. In one of the preferred embodiments of this invention, chemicals and/or a test strip is integrated within the sample collection device. DESCRIPTION OF THE PRIOR ART
  • the analysis and testing of fluid samples for detection of constituents thereof generally involves initially obtaining a representative sample, and the tran ⁇ port of the sample to a laboratory for constituent analysis.
  • the sample is collected via some expedient and transferred to an intermediate for storage and/or contact with one or more analytical reagents.
  • a representative sample is initially obtained and placed in a suitable container and the container either sealed for later testing, or transported to a remote laboratory for testing.
  • the vessel containing the sample must be both conservative of the sample and preferably adapted for later dispensing thereof to avoid any contamination of the sample and of the testing environment.
  • the sample is typically collected by invasive procedure ⁇ (e.g. finger stick or venous puncture of sample donor for a blood sample) , or as a biological waste (e.g. urine or stool specimen), depending upon the analyte of interest, and the physical condition of sample donor.
  • invasive procedure e.g. finger stick or venous puncture of sample donor for a blood sample
  • biological waste e.g. urine or stool specimen
  • the traditional methods for the invasive collection of biological fluid samples e.g. drawing blood
  • the securing of a sample such as by drawing blood, necessarily involves the consent of the subject, and is limited in terms of the size of the sample that can be obtained.
  • the sample obtained In the case of a breathalyzer type test, the sample obtained, by its very nature, is limited in the type of analyte that can be present therein, and i ⁇ otherwise difficult to preserve and/or store.
  • a vital, biological fluid such as saliva, i ⁇ relatively easily obtained, ⁇ table, conveniently stored and contains a number of analytes of interest to both the clinician and to law enforcement.
  • the sample can be readily obtained by swabbing the buccal epithelial tissues in the donor's mouth, or through the use of a saliva collection device which i ⁇ placed in the donor's mouth for a definitive period of time to allow for the adsorption of ⁇ aliva thereon.
  • T e collection of ⁇ aliva in the latter fashion, is preferred in that it protects the individual collecting the sample from exposure thereto, and otherwise provides a relatively sterile medium in which to transfer the sample for storage, or to subject the sample to analysis.
  • a number of patent references are discussed hereinafter as repre ⁇ entative of the state of the art.
  • the device described in the '502 patent (as illustrated in Figures 7 and 8) comprises an absorbent material in the nature of a wick, which is placed in the saliva donor's mouth, allowed to remain therein until e ⁇ entially saturated, and, thereafter, is removed.
  • the absorbent wick is associated with a capillary tube, which surrounds the absorbent material and provides it with a degree of physical integrity.
  • an indicator is also provided within the device, which confirm ⁇ the presence of saliva and other con ⁇ tituents therein. The device de ⁇ cribed in the '502 patent is purportedly useful for HIV testing and for drugs of abuse (to the extent present in the saliva) .
  • Alternative embodiments of the saliva collection device of the '502 patent comprise a cotton swab which is used to collect and transfer a saliva ⁇ ample from the mouth of the donor to a test ⁇ ite (absorbent sheet or layer) , which contains an indicator that can interact with the saliva and/or constituents contained therein.
  • a test ⁇ ite asbsorbent sheet or layer
  • the embodiments described in the '502 patent do not provide an effective means for both isolating and dispensing the sample and, thereafter, conveniently preserving the unused portion of the sample for later use and/or testing.
  • the u ⁇ e of a cotton swab is inherently incompatible with the collection and analysis of proteinacious analytes, or protein bound analytes, in that such materials adsorb (retain, interact, etc.) the protein and thereby prevent its later release for detection and analy ⁇ is.
  • plastics col 11, lines 13-21
  • saliva saliva for constituent analysis has and continues to be the ⁇ ource of considerable interest and investigation because of the presence of numerous analytes in saliva and it? accessibility as a ten specimen.
  • Un ortunately, the deficiencies in the techniques and devices for it ⁇ collection has up to now po ⁇ tponed it ⁇ wide ⁇ pread acceptance a ⁇ the biological ⁇ ample of choice.
  • thi ⁇ the principal object of thi ⁇ invention to provide a ⁇ imple, yet effective device for the collection, recovery and dispensing of fluids, including vital, biological fluid sample ⁇ , ⁇ uch as saliva, which is both conservative of the sample and yet provides ease of access thereto for on-site testing and analysis.
  • Additional objects of this invention include test kits and methods for on-site sample collection and testing of vital biological fluids, specifically test kits and methods for detection of infectious disease (HIV, HB ⁇ AG, etc.), drug ⁇ of abuse (cocaine, a phetamine ⁇ , barbiturates, etc.) and therapeutic drugs (theophilin, digoxin, phenobarbital, etc. ) .
  • infectious disease HIV, HB ⁇ AG, etc.
  • drug ⁇ of abuse cocaine, a phetamine ⁇ , barbiturates, etc.
  • therapeutic drugs theophilin, digoxin, phenobarbital, etc.
  • a simple yet effective device for the collection, recovery, dispensing, testing and/or storage for fluid samples, such as saliva which includes a sample recovery container (12) having an open end (12o) and a closed end (12c); a closure (14) having mean ⁇ (13) for engagement and ⁇ ealing of the open end (12o) of the sample recovery container (12); and, a sample (e.g. ⁇ aliva) absorbent element (16) affixed to the inner surface (e.g. internal webbing) of the clo ⁇ ure (14) and extending therefrom into the sample recovery container (12).
  • a sample recovery container (12) having an open end (12o) and a closed end (12c
  • a closure (14) having mean ⁇ (13) for engagement and ⁇ ealing of the open end (12o) of the sample recovery container (12)
  • a sample (e.g. ⁇ aliva) absorbent element (16) affixed to the inner surface (e.g. internal webbing) of the clo ⁇ ure (14) and extending therefrom into the sample recovery container (12
  • the sample recovery container (12) is a tubular member having an open end (12o) and closed end (12c); the closure (14) i ⁇ adapted to engage and ⁇ eal the open end (12o) of the ⁇ ample recovery container; and, a ⁇ ample ab ⁇ orbent element (16) i ⁇ a bibulou ⁇ member comprising a polymer foam of sufficient size and void volume to absorb a fluid sample which is recoverable therefrom in sufficient quantity to permit analysis and te ⁇ ting thereof without elaborate sample preparation or laboratory equipment and utilizing available methods and techniques.
  • the closure (14) include ⁇ a vent or channel (11) in the closed end (14c) thereof which permits acces ⁇ to a fluid within the tubular member 12.
  • This vent or channel (11) in the closure (14) is essentially restrictive of fluid transfer under ambient conditions, thus requiring that a negative or positive pressure be exerted upon the fluid within the tubular member to effect the passage thereof through the vent or channel (11) in the closure.
  • the closure (14) is of composite construction, and is composed of an essentially open cylinder having an internal screw thread for engagement with a complimentary thread on the tubular container, and a closed end (14c) defined by a snap-in disk or accessory 15 also having at least one hole or channel (11) therein.
  • This snap-in element (15) can take the form of a bottle dropper or have other functional attributes which are discu ⁇ ed herein.
  • the ⁇ ample ab ⁇ orbent element (16) be matched to the physical and chemical propertie ⁇ of both the fluid sample and the analytes contained therein, in that it must be both capable of ab ⁇ orption and relea ⁇ e of the sample and constituents of interest to allow for analysi ⁇ thereof without any substantial interaction or adsorption thereof.
  • the sample absorbent element (16) is an open cell polymer foam (prepared from a HYPOL brand urethane pre-poly er, available from W.R.
  • Thi ⁇ foam (and other comparable materials), can be formulated, as desired, to have the requisite density and other physical properties consistent with the inherent characteristics of the absorbed fluid, and the contemplated method of sample recovery and analysi ⁇ .
  • the physical size and shape of the absorbent foam element (16) roughly parallels the shape of the chamber defined by the housing, and yet has a comparatively small profile (generally 50 to 60% of volume of the collection tube).
  • the sample recovery component of the collection device comprises a tubular element (12) composed of a resilient elastomeric material and is preferably provided on the closed end (12c) thereof with functional tip (20) that includes a reservoir (19) which can collect the saliva if and when it is expressed from the sample ab ⁇ orbent element.
  • the closed end (20c) of the functional tip (20) can be opened and thereafter resealed.
  • This functional tip (20) is optionally provided with one or more indices (not shown), or graduation marks, corresponding to fluid volume, (analgous to a pipette), and, thus, can be used to dispen ⁇ e a metered amount of fluid ( ⁇ aliva) by simply squeezing the housing.
  • either the clo ⁇ ure (14) and/or the functional tip (20) of the tubular element can be further modified to provide a fitting (18) for coupling or phy ⁇ ically engaging (mating with) a fixture (21) which includes an analyte sensitive element (80).
  • each of the closure (14) and/or the functional tip (20) of the sample recovery container of the collection device, and a fixture (21) for an analyte sensitive element can each be modified to engage the other so as to create leak proof union of the two and thereby provide a fluid pathway from the tubular element to a fluid receiving component of the fixture for the analyte sen ⁇ itive element.
  • recovery of the fluid sample from the fluid absorbent element (16) e.g. squeezing the foam
  • it can be directly applied from the reservoir within the sample recovery tube onto the test element without any loss or inadvertent contact with the clinician.
  • the balance is conserved for re-testing or simply retained within the secure environment of the collection device, thus insuring against its cross-contamination and/or infection of unsuspecting individuals.
  • the volume of saliva that is collected by the fluid absorbent element (16) is a function of both the size of the absorbent element (16) and, of course, the time the element is in contact with the donor.
  • a typical saliva collector of this invention has a fluid ab ⁇ orbent element (16) of sufficient ⁇ ize and fluid capacity to absorb and thereafter release (express) a sufficient volume of saliva (from about 100 to 200 microliters) for performance of at least one screening a ⁇ ay and at lea ⁇ t one conformation assay (should that be required).
  • the volume of sample contemplated for use in the solid phase immunoassays of interest will generally require at least 50, and preferably, 100 microliters.
  • the test kit of this invention includes at least one analyte sensitive element and at least one sample collection device of this invention along with instructions for the performance of an analysis of the collected fluid sample.
  • one or more additional reagents can accompany the analyte ⁇ ensitive element.
  • the preferred test kit of this invention includes a physically discrete fixture (e.g. having an analyte sensitive element) which is uniquely designed to be aligned and/or to couple with the foregoing sample device and thereby provide a direct and convenient means for transfer of the fluid contents from the collection device so as to permit its analysis.
  • test kit can simply include an analyte sensitive element and/or interactive chemicals within a housing that is common to the sample absorbent element, wherein each are maintained isolated from the other until the appropriate time for transfer of the sample to the analyte sen ⁇ itive element.
  • Fig 1. is a perspective view of a preferred embodiment of a sample collection device of this invention
  • Fig. 2 is an exploded view of the sample collection device of Fig. 1, which includes a sample recovery or collection tube and closure of composite construction;
  • Fig. 3A depicts an enlarged view of the composite closure of Fig. 2a, wherein the closed end of the clo ⁇ ure comprises a disk insert having an orifice which defines a fluid pathway through the insert;
  • Fig. 3B depicts an enlarged top view of the open end (threaded member) of the composite closure of Fig. 3A.
  • Fig. 4A depicts an alternative insert for the composite closure of Fig. 2A, wherein the insert is configured for dispensing an aliquot of ⁇ ample from the collection device subsequent to its recovery thereof;
  • Fig. 4B depicts an alternative insert for the compo ⁇ ite closure of Fig. 2A, wherein the insert includes a fitting that is configured for docking with a fixture which can include an analyte sensitive element;
  • Fig. 5 depicts a sample collection device wherein the clo ⁇ ed end of the tubular component include ⁇ a ⁇ kirt;
  • Fig. 6A depict ⁇ a sample collection device wherein the clo ⁇ ed end of the tubular component include ⁇ pipette tip;
  • Fig. 6B depict ⁇ a sample collection device wherein the closed end of the tubular component includes a tapped dispensing tip having an internal pressure activated valve;
  • Fig. 6C depicts a sample collection device wherein the closed end of the tubular component includes a reagent tip and an accessory cuvette for uses in conjunction with the collection device;
  • Fig. 7A depicts an alternative embodiment of the sample collection device of Fig. 5, wherein the collection tube (12) i ⁇ modified on the closed end thereof to accept an in ⁇ ert of the type illustrated in Fig. 4A;
  • Fig. 7B depicts an exploded view, in part, of the sample collection device of Fig. 7A;
  • Fig. 8A depicts an alternative embodiment of the sample collection device of Fig. 5, wherein the collection tube is modified on the closed end thereof to accept an insert of the illustrated in Fig. 4B;
  • Fig. 8B depicts an exploded view, in part. >->f the sample collection device of Fig. 8 ⁇ :
  • Fig. c depicts ⁇ _- sam u collection device of Fig. 8A in docking relationship with a syringe;
  • Fig. 10 depicts the sample collection device of Fig. 5 in docking relationship with a Vacutainpr-like syringe;
  • Fig. 11 depicts the sample collection device of Fig. 5 in cooperative relationship with a te ⁇ t icon
  • Fig. 12 depicts an alternative embodiment of the sample collection device of Fig. 1 wherein the sidewall of the tubular component includes a reagent coating specific for interaction with one or more constituents of the sample;
  • Fig. 13 depicts the sample collection device of Fig. 1 in a "test kit;" and Fig. 14 depicts the test kit of Fig. 13 in a
  • the design and operation of the various components of the sample collection device all cooperate to collect a fluid sample in sufficient volume a ⁇ to be representative of the environment from which it has been obtained, and thereafter permit recovery of an aliquot of such fluid for constituent analysis.
  • the device of this invention incorporates these multiple functions into a single, yet simple design. More specifically, the basic structure of the device (110) is illustrated in Fig.
  • sample recovery tube 112 generally include ⁇ four (4) functional components, specifically a collection (sample recovery) tube (112), a closure (114) for the collection tube (112), a sample absorbent foam element (116) for collection (adsorption) of the liquid sample, (e.g. a biological fluids sample such a ⁇ ⁇ aliva) and a means (111) for accessing the sample recovery chamber within the device (110) so as to permit dispensing of an aliquot of the sample without removal of the closure (114).
  • sample recovery tube (112 specifically a collection (sample recovery) tube (112), a closure (114) for the collection tube (112), a sample absorbent foam element (116) for collection (adsorption) of the liquid sample, (e.g. a biological fluids sample such a ⁇ ⁇ aliva) and a means (111) for accessing the sample recovery chamber within the device (110) so as to permit dispensing of an aliquot of the sample without removal of the closure (114).
  • the sample absorbent foam element (216) is integrated into the closure (214) and the closure (214) is of composite construction.
  • the composite nature of the closure is further illustrated in Figs. 3A and 3B. More ⁇ pecifically, the closure (314) includes a closed end (314c) and open end (314o) which are structural and functionally unique.
  • the open end (314o) of the closure (314) i ⁇ characterized as an es ⁇ entially cylindrical element having means (313) for engaging and sealing the collection tube.
  • each of the collection tube (212,312) and the closure (214,314) is provided with a complementary thread (209).
  • the closed end (214c,314c) of the closure (214,314) is provided with a recess, or equivalent detente, (217,317) for acceptance of a disk-like insert (215,315).
  • the insert (215,315) i ⁇ complementary with the rece ⁇ (217,317) in the clo ⁇ ed end (214c, 314c) of the closure (214,314) so a ⁇ to form a locking seal between the insert and the rece ⁇ /detente.
  • FIG. 4A Alternative embodiment ⁇ of this closure insert of Figs. 2 and 3 are depicted in Fig ⁇ . 4A and 4B. More specifically, the closure insert depicted in Fig. 4A can take the form of a dropper bottle tip (415), and thu ⁇ permit the di ⁇ pensing of an aliquot of a recovered sample from the reservoir of the collection device onto an analyte sensitive element, or into a cuvette, for constituent analysis of the sample.
  • a closure insert design which includes a fitting (418) adapted for docking with a fixture (432) for an analyte sensitive element that is capable of manifesting the presence of the analyte of interest, if present in the sample.
  • the closure insert (115) is designed to provide a le ⁇ s than air tight seal, or have a hole/channel (111) therein to permit the vapor and/or gas (e.g. air) that is trapped within the sample recovery tube (112) to be expelled at the time of expres ⁇ ing the ⁇ ample from the ⁇ ample absorbent medium into the sample recovery tube (112).
  • gas e.g. air
  • the term "fluid" a ⁇ used in conjunction with the term ⁇ "hole” and "channel,” is inclusive of both liquids and gase ⁇ .
  • the ⁇ ize, ⁇ hape and location of a hole/channel (111) in the cap allows for both the compression of the collection tube (112) during the recovery of the sample and it ⁇ return to original ⁇ hape.
  • the sample ab ⁇ orbent foam (116) remains firmly affixed to the internal structure of the closure (114).
  • the device (110) of thi ⁇ invention can be used in a variety of environments and thu ⁇ its ⁇ pecific construction will be dictated accordingly. More specifically, where thi ⁇ device (110) i ⁇ to be used to collect a fluid sample containing a hazardous waste comprising a highly acidic ⁇ ub ⁇ tance of organic ⁇ ub ⁇ tance, the material ⁇ selection for the components of the collection device (110) u ⁇ t be re ⁇ i ⁇ tant to degradation by the sample.
  • the materials selection for the collection tube and the sample absorbent element (116) must be suitable to this task - inactive relative to proteins and constituents (collectively "analytes" of the sample.
  • the sample absorbent element (116) cannot be ingested or subject to breakdown from the enzymes contained in the saliva or otherwise include any substance that can be leached from the element (116) during IA
  • sample absorbent element (116) used in the collection of the saliva are thus critical to both the efficacy of the device, specifically the ability to absorb and thereafter release the biological fluid to allow for the analysis of the constituents contained therein.
  • the sample absorbent element (116) for a saliva collection device (110) of this invention is an inert (e.g. cross ⁇ linked) plastic which is prepared from a pre-polymer which i ⁇ processed to produce an open cell foam having characteristics consistent with the foregoing sample collection and analysis requirements.
  • the absorbent foam element (116) i ⁇ formed of a water catalyzed polyurethane pre ⁇ polymer, of the type available from Hamp ⁇ hire Chemical Corporation, a ⁇ ub ⁇ idiary of W.R. Grace, under the HYPOL trademark.
  • HYPOL brand polyurethane pre-polymer ⁇ can be synthesized in accordance with the materials and procedures described in US Patent 3,903,232 (which is herein incorporated by referenece in its entirety).
  • the processing conditions and composition of the foam are geared to provide a very high adsorption den ⁇ ity (open cell foam) and sufficient tensile strength to withstand the rigors of sample collection and thereafter the recovery thereof by the compression of the foam so as to express the sample into the sample recovery tube where it can be contacted with an analyte sensitive element or dispensed onto a test strip analysis.
  • this material must also be chemically inert (relative to the sample) and devoid of any unreactive and/or labile materials which can be ingested during the process of sample collection.
  • this foam composition can be prepared from a hydrophilic cross linked polyurethane foam by interaction of an isocyanate terminated polyethylene polyol with large amounts of an aqueous reactant. The resultant foams produced thereby can be molded to size and/or compressed. These foams are characterized as a low den ⁇ ity polyurethane foam (one to about three pounds per cubic foot) which is readily compressible to about one- i teenth to about one twentieth its original ⁇ ize.
  • foams can be synthe ⁇ ized by initially capping (terminating) a polyoxyethylene polyol with an isocyanate.
  • this proces ⁇ involves reacting a polyoxyethylene polyol with a polyisocyanate in a non-o idizing atmosphere (nitrogen) , at atmospheric pressure within a temperature range from about 0°C to about 120°C for a period of time of about twenty (20) hours, depending upon the temperature and the degree of agitation of the interactive constituent ⁇ .
  • the polyi ⁇ ocyanates used for capping the polyoxyethylene polyol include polyisothiocyanate ⁇ , polyi ⁇ ocyanate ⁇ which are PAPPI I(polyaryl polyi ⁇ ocyanate as defined in US Patent No.
  • tolylene dii ⁇ ocyanate triphenylmethane - 4, 4 ' ,4", trii ⁇ ocyanate, benzene-1 , 3 , 5-trii ⁇ ocyanate, hexamethylene diisocyanate, xylene diisocyanate, chlorophenylene diisocyanate, diphenylmethane-4, '-diioscyanate, naphthalene-1 , 5-diisocy anate, xylene-alpha, alpha-diisothiocyanate 3 ,3 'dimethyl- 4, 4 '-biphenylene diio ⁇ ocyanate, 4, 4 '-methylenebi ⁇ (Phenyl- isocyanate), 4, '-sulfonylibi ⁇ (phenylisocyanate) , 4, J- methylene diorthotolylisocyanate, ethylene diisocyanate, ethylene diisothiocyanate
  • organic isothiocyanates or isocyanates may be used as de- sired.
  • aromatic diisocyanates and polyisocyanates or mixtures thereof which are especially suitable are those which are readily commercially available, have a high degree of reactivity and a relatively low co ⁇ t.
  • Capping of the polyoxyethylene polyol may be accomplished using stoichiometric amounts of reactants. Desirably, however, an excess of isocyanate is used to ensure complete capping of the polyol.
  • the ratio of isocyanate groups to the hydroxyl groups used for capping is between about 1 to about 4 isocyanate to hydroxyl, and preferably about 2 to 5 about 3 isocyanate to hydroxyl molar ratio.
  • the active components may be formulated in one of the following by way of example.
  • the isocyanate capped polyoxyethylene polyol reaction pro- duct must have an average isocyanate functionality greater than 2 and up to about 6 or more depending upon the compo ⁇ sition of the polyol and capping agent components.
  • the aqueous reactant may contain a dissolved or disper ⁇ ed iso ⁇ cyanate-reactive cros ⁇ -linking agent having an effective greater than two.
  • the reactive cro ⁇ linking agent i ⁇ reacted with the capped polyoxyethylene polyol when admixed during and after the foaming process has been initiated.
  • a polyisocyanate cross-linking agent having an isocyanate functionality greater than two may be incor ⁇ porated therein, either preformed or formed in ⁇ itu, and the re ⁇ ultant mixture may then be reacted with the aqueou ⁇ reactant, optionally containing a di ⁇ olved or dispersed reactive isocyanate-reactive cross-linking agent, leading to a cros ⁇ -linked, infinite network hydrophilic polyur ⁇ ethane foa .
  • the sample absorbent element is formed by simple and well-known fabrication methods.
  • foams can be formed for fluid sample absorbent element of this invention from the foregoing HYPOL like pre-polymer ⁇ , utilizing technique ⁇ analogou ⁇ to those described in US Patent 4,944,947 (to Newman), which is incorporated by reference in its entirety.
  • Newman patent describe ⁇ fabrication of a dental appliance from a HYPOL foam pre-poly er (HYPOL FHP- 2002), which i ⁇ simply added to an aqueou ⁇ medium at an elevated temperature (110°F,38°C) , and thereafter stirred vigorously until frothy.
  • the closure (314) is initially affixed to the mold (not shown) and the ⁇ ample absorbent element (316) formed by injection of the foam into a mold through the top of the clo ⁇ ure (314). As the foam expands, it fills the mold and flows into the closure.
  • sample recovery tube (112,212) of the collection device (110,210) of this invention can have a simple round bottom configuration, depending upon it ⁇ intended uses, a flexible (and resilient) sidewall construction and versatility for configuration with other functional components of the device.
  • the sample recovery tube (112) can be prepared from a relatively rigid material, (e.g. thermoset plastic).
  • the sample recovery tube (112) has an open end (112o) and a closed end/or sealed end (112c).
  • the open end (112o) is of sufficient diameter to accommodate the in ⁇ ertion and removal of the sample absorbent element (116), and is further provided with external threads, or an equivalent expedient, for sealing engagement by a screw cap or comparable closure (114).
  • the sample collection device (510) illustrated in Fig. 5 comprises a skirted tube (512).
  • the closed/sealed end of the sample recovery tube (512) of the collection device (510) of this invention can include various means for accessing the fluid from within the tube, and for resealing the closed end of the sample recovery tube after an aliquot of the sample has been obtained.
  • the sample recovery tube (612) i ⁇ provided on the clo ⁇ ed end (612c) thereof with a di ⁇ pen ⁇ ing tip (620) that can be opened and resealed.
  • the tip can be re-sealed by simply heating the tip until it melts, or with an appro- priate closure designed for that purpose.
  • the inclusion of an internal pressure activated valve (621) of the type shown in Fig. 6B eliminates the need for re-sealing of the dispensing tip (620). More specifically, upon exertion of pres ⁇ ure on the content ⁇ of the ⁇ ample recovery tube (612) the valve (621) i ⁇ forced to open and thereby permits the flow of fluid from within the sample recovery tube. In the absence of such pressure, the dispensing tip (620) remains sealed and the contents of the tube ⁇ ecure.
  • Fig. 6C depicts yet another alternative embodiment of the sample recovery tube (612) wherein a distinct chamber (622) i ⁇ formed in the clo ⁇ ed end of the ⁇ ample recovery tube.
  • the closed end (612c) of the sample recovery tube (612) can be modified as illustrated in Fig. 6C to incorporate a plurality of septa (623,624) to define one or more chambers (622) at or near the terminus (620) of closed end (612c) of the tube (612).
  • a typical chamber can contain a liquid material (624) (e.g., chemistry ⁇ y ⁇ tem) specific for interaction with a constituent of the sample incident to the analysis thereof; and/or to supplement the volume or dilute the sample.
  • This latter embodiment of the invention further contemplates the u ⁇ es of an additional accessory in the nature of a cuvette (625) which, in the embodiment of the invention depicted in Fig. 6C, includes a piercing member (e.g. needle) (626) to puncture the septa (623,624) of the chamber(s) (622) in the di ⁇ pensing tip (620) and thereby cause the sample and the contents of the chamber (624) to commingle and flow into the cuvette (625) where they are combined.
  • the sample recovery tube (612) can be squeezed to assist the flow of fluid through dispen ⁇ ing tip into the cuvette (625).
  • the cuvette (625) u ⁇ ed in this embodiment of the invention can comprise a rigid device which includes an optical window (626), or be composed of re ⁇ ilient material that i ⁇ compliant with a read station of a monitoring instrument (not shown).
  • the sample recovery tube (112) of the collection device (110) of the type depicted in Fig. 1 i ⁇ preferably of a flexible side ⁇ wall construction, and transparent to allow for ob ⁇ ervation of the ⁇ ample within the sample recovery tube (112).
  • the tube is sealed with the closure (114).
  • the ⁇ ides of the ⁇ ample recovery tube are ⁇ queezed ⁇ o as to co pres ⁇ the sample absorbent element therein and thereby express the sample from the sample absorbent element into a re ⁇ ervoir (112r) provided at the closed end (112c) of the sample recovery tube (112).
  • the sample recovery tube (712,812) can comprise a composite characterized by an elongate barrel having an open end (712o,814o) and a closed end (712c,814c).
  • the open end (714o,814o) of the tube i ⁇ essentially the same as the tube of unitary structure depicted in Fig. 1 (e.g.
  • the composite sample recovery tube (712,812) of the collection device (710,810) of this invention can have a solid member as snap-in insert (770,870) in the closed end (712c,812c) thereof , which can be replaced with a functional accessory, as appropriate. More specificaly, the closed end (712c,812c) of the sample recovery tube (712,812) illustrated in Fig.
  • a recess or detente (717,817) formed within the barrel of the tube at the terminus of the tube.
  • This recess/detente (717,817) is designed to receive a snap-in insert (715,815) which can include a functional accessory (e.g. dispensing tip) of the type depicted in Fig. 7A and B or, alternatively, the snap-in insert can include a fitting (718,818) designed for docking with a fixture and/or a syringe such as is depicted in Fig. 4B and Fig. 9 respectively.
  • the choice of insert can tailor the utility of the sample collection device (710,810) to the particular needs and environment contemplated for its use.
  • the sample collection device (910) of this invention is provided with a closure (914) of compo ⁇ ite construction, which includes a fitting (918) adapted for docking with a syringe (950).
  • a fitting (918) adapted for docking with a syringe (950).
  • the contents of the syringe can be injected into the sample recovery tube (912) or, alternatively, the sample is acces ⁇ ed from the ⁇ ample recovery tube (912) through the closure, by the syringe.
  • this fitting can be designed for docking with any one of a number of complimentary devices and/or acces ⁇ ories which permit access to the sample without removal of the closure (914) or piercing of the sample collection device.
  • the sample can be accessed from within the sample recovery tube by piercing the tube with a hypodermic needle/syringe setup. More specifically, the syringe used in the embodiments of this invention, once equipped with a hypodermic needle can easily puncture the tube and/or be inserted through the hole/channel in the closure to withdraw fluid from within the sample recovery tube.
  • the foam that is entrained within the webbing of the closure functions much in the same way as septa of a vial, by permitting insertion of the needle into the tube and yet effectively re-sealing the tube at the time the needle is withdrawn.
  • a Vacutainer-type syringe is placed in proximate relation to the closed end of the sample recovery tube and upon puncture of the container effects withdrawal of sample from within the sample recovery tube. More specifically, once the sample has been recovered from the sample absorbent element, it can thereafter be acces ⁇ ed from the sample recovery tube (1012) by simply puncturing the closed end (1012c) of the tube with a needle (1026) associated with a syringe (1050) and an aliquot of the sample withdrawn through the needle into a syringe.
  • the barrel (1051) of syringe (1050) is under a negative pressure thereby effecting withdrawal of the sample. A ⁇ an aliquot of the ⁇ ample is withdrawn from the sample recovery tube (1012), the tube (1012 will deform thu ⁇ permitting an uninterrupted flow of sample into the syringe (1050).
  • Alternative methods for accessing an aliquot of the sample from the sample recovery tube include the provision of a needle (1126) integral with a te ⁇ t device (1160) which houses an analyte sensitive element.
  • the needle (1126) in test device punctures the closed end (1112c) of the sample recovery tube.
  • An aliquot of the sample is thereby accessed and can be applied to the analyte sensitive element by simply squeezing the sample recovery tube (1112) so as to cause the sample to flow down the grooves (not shown) in the needle and thereby initiate an analyte manifesting reaction within the analyte sensitive element in the test device.
  • the interaction of the constituents of the sample with analyte manifesting reactants can be accomplished entirely within the sample recovery tube (1212), without removal of the clo ⁇ ure (1214) from the sample collection device (1210), by initially coating such reactants (1280) on the interior sidewall of the tube at the time of assembly and thereafter drying such reactants (1280) on the interior sidewall of the tube at the time of assembly and thereafter drying such reactants on the tube wall.
  • the constituents in the sample may be measurable due to some intrin ⁇ ic property, or alternatively, are manife ⁇ t once having been combined with another substance which is present in the collection tube (1212) and/or added to the collection tube.
  • chemical substances (1280) can be coated on the interior of the collection tube (1212) and freeze dried.
  • the chemicals Upon introduction of the sample absorbent medium into the tube and the recovery of the fluid ab ⁇ orbed thereof by ⁇ queezing the ⁇ idewall ⁇ thereof in the direction indicated by the arrows, the chemicals are reconstituted and interact with the analyte of interest in the sample to produce a discernible change therein which is indicative of the analyte of interest.
  • the chemicals can be present as an encapsulant (e.g. frangible microspheres) on the interior of the collection tube (1212). r .hu.-..
  • microspheres (1280) upon squeezing of the sidwalls of the tube incident t ⁇ _ recovery of the sample from the sample absorbent medium, these microspheres (1280) are ruptured and the chemical agent ⁇ contained therein are released and interact with one or more constituents in the sample to produce a detectable species that is indicative of the presence of the analyte in the sample.
  • the reactants are reconstituted by the sample and thereupon interact with the constituent ⁇ of the sample so as to produce a discernible change within the sample recovery tube (1212) that is indicative of the analyte of interest.
  • This discernible change within the tube (1212) can include the formation of a distinctive color, increase in the turbidity in the fluid phase of the sample, formation of bubbles, formation of a precipitate, and or/ a combination of both.
  • chemical agents can be entrained within the sample absorbent medium and not released unless and until the appropriate sequence in the analytical proces ⁇ .
  • the sample is a biological fluid such as saliva
  • the u ⁇ e of chemical reagents in the tube and/or in conjunction with the absorbent medium must be approached with caution.
  • the sample is obtained by contact (or immersion) of a ⁇ ample ab ⁇ orbent medium with a ⁇ ource of a fluid ⁇ uspected of containing an analyte of interest.
  • a representative ⁇ ample of the wa ⁇ te water i ⁇ obtained and the sample absorbent medium simply immersed within the sample.
  • the amount of the sample that need be absorbed to perform the desired analysis is determined utltimately by the analytical protocol, and it is as ⁇ umed thi ⁇ immer ⁇ ion procedure will supply more than adequate sample for the intended analysi ⁇ .
  • the device of thi ⁇ invention is to be used to collect a biological fluid sample (e.g. saliva) through contact of the sample absorbent medium with a sample donor
  • a biological fluid sample e.g. saliva
  • the contact must be of sufficient duration to allow for ad ⁇ orption of a representative sample and, preferably, be obtained under "normal” conditions (a ⁇ compared to a ⁇ aliva ⁇ ample that is through the use of flavored element - " ⁇ timulated” sample) .
  • the sample absorbent medium of the device (110) of this invention can be readily adapted to the age of the donor (infants, toddlers, adults) and otherwise have varying porosity to make it more or les ⁇ absorbent.
  • this device (110) can be used with the other traditional biological fluids, (e.g. urine, whole blood, serum, etc.) and its design may thus vary accordingly.
  • the sample is obtained by first removal of the sample collection element (116) from its secure environment within the collection tube (112), the sample collected as above de ⁇ cribed and the sample collection element (116) sealed within the collection tube. A ⁇ suming that an adequate (by volume) sample has been obtained, it can thereafter be expressed by any one of a number of techniques, depending upon the configuration of the device (110) of this invention, and once recovered, subject to con ⁇ titutent analysis.
  • the collection and recovery of a representative sample of fluid is accomplished with relative ease and security.
  • the closure obviously can be removed from the device to permit access to the sample with the sample recovery tube, and an analyte sensitive element and/or chemicals added into the sample recovery tube and allowed to interact with the recovered sample.
  • This method of analysis is generally unde ⁇ irable since it needles ⁇ ly exposes the clinician and the environment to the used sample ab ⁇ orbent element and the content ⁇ of the sample recovery tube.
  • the preferred embodiment of the device ⁇ elected will insure that once the sample has been obtained, it is retained within the secure environment of the collection tube and thereafter only supplied for analysis in a manner that prevents contamination of the ambient environment and those persons that must have access thereto for purposes of analysis.
  • the sample is generally obtained by first expressing the sample from the sample absorbent foam element into a reservoir at the closed end of the sample recovery tube, and then removing the closure from opening of the sample recovery tube of the collection device, (which also results in the sample absorbent element withdrawn from the recovery tube) .
  • An aliquot of fluid sample can thereafter be withdrawn from the sample collection tube with a pipette, or the sample simply transferred to another vessel for analysis, by pouring the sample from the tube into the te ⁇ t vessel.
  • the sample absorbent element and the closure are re-united with the sample recovery tube and the tube sealed with the closure.
  • the flexible sidewall design of the collection tube permits the recovery of the ⁇ ample from the sample absorbent foam element by compressing the foam within the tube, where it collects in the re ⁇ ervoir in the bottom (clo ⁇ ed end) of the tube.
  • the volume of air confined within the tube i ⁇ preferably di ⁇ placed to allow for ease of compres ⁇ ion of the ⁇ ample recovery tube and the ⁇ queezing of sample absorbent foam element within the tube to be readily and most efficiently collection compres ⁇ ed.
  • the sample recovery proces ⁇ is inefficient, requires substantial pressure to squeeze the tube and express the sample, can cause potential damage to the tube and to the clo ⁇ ure and generally recover ⁇ less sample from the sample absorbent element.
  • the provision of a vent/channel in the closure dramatically improves the sample recovery proces ⁇ without compromising the sealing of the device or requiring excessive squeezing of the collection tube, thus minimizing the potentiality for damage to collection device during the sample recovery process.
  • the collection and recovery of the sample within the device of this invention i ⁇ only the beginning of the process for the determination of the presence of the analyte of interest, and, in some instances, the amount thereof.
  • an aliquot of sample is contacted with an analyte sensitive element that is specific for the manifestation of the presence of the analyte of interest.
  • the analyte ⁇ ensitve element can be one or more chemicals that are reactive with the analyte of interest, or alternatively, an elaborate chemistry system.
  • the analyte sensitive element can be contacted directly with the sample by the placement thereof into the collection tube, or an aliquot of sample withdrawn/di ⁇ pen ⁇ ed from the ⁇ ample recovery tube and reacted with the analyte ⁇ ensitive element in a test environment that is independent of the collection device of this invention.
  • an aliquot of sample can be removed from the sample recovery tube through the use of a pipette or straw.
  • the preferred sample handling routine involves the u ⁇ e of one or more of the acce ⁇ ory inserts to modify the closure or the sample recovery tube to enable dispen ⁇ ing of a recovered sample without removal of the closure and the sample absorbent element from the sample recovery tube.
  • the sample recovered with the device of thi ⁇ invention can be subjected to analysis by one or more test protocols for determination of the presence and/or amount of the constituents of interest.
  • a test kit (1300) of the type in the illustration in Fig. 13 is provided which generally includes the sample collection device (1310) and all of the accessories (e.g. unit packages of reagents) (1380) and reagent system (1360) needed to complete the desired analysis.
  • the manner in which such components are arranged and presented is often critical to proper and consistent test results, particularly when such test is to be performed by relatively unskilled personnel and at a location remote from a clinical laboratory. Accordingly, this invention includes, as illustrated in Fig.
  • test kit package (1400) which provides a series of recesses (1490) and instructions associated with the package for arranging the kit components in a "work station” format to insure proper sample and reagent utilization and consi ⁇ tent te ⁇ t re ⁇ ults.
  • Example I_ 1 Fabrication of Sample Collector -
  • a sample recovery tube is initially obtained from Precision Laboratory Plastics (Centrallia, WA) .
  • This tube ha ⁇ a flexible sidewall, i ⁇ essentially transparent, closed on one end and open on the opposite end.
  • This sample collection tube is approximately 3 inches in length and has an in ⁇ ide diameter of 0.5 inche ⁇ .
  • the open end thereof i ⁇ provided with external threads for sealing engagement with a clo ⁇ ure (screw cap) of the type depicted in Figure 3.
  • a sample absorbent element i ⁇ prepared by molding a hydrophilic polyurethane foam compound (HYPOL FHP 2002, available from W.R. Grace, Boca Raton, FL) , utilizing the tube of the collection device as a form. More specifically, a foam element is fabricated by injection of a foam compound through the open end of the closure into the collection tube, allowing the foam to expand within the tube and into the webbing of the closure. As the foam cures, it shrinks within the tube, thereby providing a space between the sample absorbent foam and the sidewall of the tube. The foam also shrinks in the long dimension thereby providing a reservoir in the end of the tube for the collection of sample. The shrinkage of the foam does not affect its attachment to the webbing of the closure, where it remains anchored. A snap-in cap (insert) is thereafter inserted into the top of the closure to complete the device .
  • HYPOL FHP 2002 available from W.R. Grace, Boca Raton, FL
  • the HYPOL foam compound selected for this application i ⁇ formulated to ⁇ hrink approximately 40%, thereby permitting the ab ⁇ orbent element to be ea ⁇ ily withdrawn and reinserted into the tube incident to the sample collection process. Since the absorbent element is integral with the closure, it does not require any further proce ⁇ ing to ⁇ ecure it. Once the foam has sufficient green strength, the cap and the foam element can be removed from the tube and inserted into the ⁇ aliva donor' ⁇ mouth and allowed to ab ⁇ orb ⁇ aliva.
  • the closure and sample ab ⁇ orbent foam i ⁇ removed from the device by simply unscrewing the closure from the collection tube.
  • the sample collection proce ⁇ can ⁇ imply involve the immer ⁇ ion of the foam into a fluid ⁇ ample or by the contact of thi ⁇ foam with a ⁇ ample donor. In the context of ⁇ aliva collection, this foam element i ⁇ placed in the donor' ⁇ mouth and allowed to remain in contact with salivary secretions for an abbreviated period of time (generally 3 to 5 minutes).
  • the salivary secretion is collected under normal conditions and that the donor's salivary glands are not stimulated by prior contact with food or other artificial means.
  • sufficient saliva at least 75 to 100 micro liters
  • the foam is removed from the donor's mouth, placed in the collection tube and the tube ⁇ eal a ⁇ before with the clo ⁇ ure.
  • the ⁇ ample can thereafter be recovered by ⁇ imply ⁇ queezing the flexible ⁇ idewall of the collection tube.
  • the physical properties of the recovered sample closely approximate those of water (saline) and thus further analysi ⁇ thereof can be accompli ⁇ hed without any additional sample preparation or treatment.
  • sample Analysis Once the sample h ⁇ been collected and recovered in the manner de ⁇ cribed above, it can be subject to analysis and testing by contacting an aliquot thereof with one or more components of a diagnostic test kit, e.g. immunoreagent ⁇ specific for interaction with one or more constituents of the sample.
  • a diagnostic test kit e.g. immunoreagent ⁇ specific for interaction with one or more constituents of the sample.
  • additional kit components include an analyte sen ⁇ itive element (Te ⁇ t Strip) and one or more additional reagents, depending upon the as ⁇ ay format and analyte of intere ⁇ t .
  • the analyte ⁇ ensitive element comprise ⁇ an HIV specific binding protein immobilized within a membrane that is supported in a hou ⁇ ing.
  • the HIV ⁇ pecific analyte ⁇ en ⁇ itive element i ⁇ available commercially, for inve ⁇ tigational u ⁇ e, from Technical Chemical & Product ⁇ , Inc. (TCPI), Ft. Lauderdale, Florida (Rapid brand) .
  • the analyte sensitive element is fabricated from a nitrocellulose membrane (Millipore Corp. ) backbone support that is spotted with the specific antigen frag ent ⁇ (i.e. pl20, gp40) that are bound to the membrane after the membrane has been prepared to accept the antigen mixture.
  • the membrane is first pre-wet with a phosphate buffer to activate the ⁇ urface and prepare it to accept the antigen ⁇ olution.
  • the antigen mixture i ⁇ di ⁇ pensed onto the membrane (2-5 microliters) so as to form a spot of 0.5-3mm in diameter.
  • the spot is then allowed to dry either naturally or in a vacuum drying oven.
  • the antigen ⁇ potted membrane is thereafter immersed in a solution containing a wetting agent and a protein (BSA or Casein) to block the unreactive sites.
  • BSA or Casein a protein
  • the resultant HIV specific membrane is then dried as above.
  • the dried membrane is mounted in a holder which contains a molded-in well and absorbent pad for absorption of exces ⁇ ⁇ ample.
  • the mounted membrane i ⁇ fir ⁇ t pre-wet with a buffer solution which is then allowed to completely absorb into the membrane and its underlying absorbent pad.
  • the next step is the addition of a colloidal gold-protein A conjugate solution.
  • One hundred (100) microliters of this conjugate solution is added to the te ⁇ t well and allowed to absorb by the membrane.
  • the final step is the addition of a wa ⁇ h ⁇ olution whose purpose is to clarify and accentuate the positive result if present.
  • a positive result is visualized by the gold solution coupling to the antigen- antibody complex formed when a po ⁇ itive antibody sample is placed in contact with the spot of antigen on the membrane and turning it red.
  • the analyte sensitive element comprises a linear test strip having a series of zones, each specific for performance of a discrete function.
  • the analyte sensitive element is available commercially, for investigational use, from Technical Chemical ⁇ & Product ⁇ , Inc., Ft. Lauderdale, Florida (Rapid brand One-Step test format).
  • the analyte sen ⁇ itive element compri ⁇ e ⁇ a ⁇ ample pad which i ⁇ integrated with and/or in fluid communication with a test strip (nitro cellulose membrane).
  • the sample collection pad is of sufficient void volume to accommodate adequate sample to perform the contemplated assay.
  • the functional areas of the membrane include a reagent zone within which is deposted (and lyophilized) an unbound (mobile) gold labeled antibody conjugate specific for interaction with the analyte of intere ⁇ t (HBsAG).
  • the sample reconstitutes the gold labeled conjugate and thereby provides a medium for the interaction between the analyte and the conjugate, so a ⁇ to form an im unocomplex.
  • a ⁇ the ⁇ ample is absorbed by the test element, it cause ⁇ thi ⁇ immunocomplex, and any exces ⁇ (unreacted) conjugate, to pass along the fluid pathway within the test element where it comes in contact with an immobilized binding substance (e.g. antibody) specific for interacting with and which includes one or more delimited areas having an immobilized binding material specific for the interaction with a con ⁇ tituent of a biological fluid sample or a reaction product which includes a constituent of the biological fluid sample.
  • an immobilized binding substance e.g. antibody
  • the analyte sensitive medium is preferably mounted in a fixture with other accessory components to a ⁇ i ⁇ t in the distribution and flow of the biological fluid sample within the analyte sen ⁇ itive element.
  • the format of the analyte ⁇ en ⁇ itive medium ⁇ uitable for u ⁇ e in thi ⁇ invention can accommodate amounts of fluids generally in exces ⁇ of that required to perform the a ⁇ ay ⁇ o a ⁇ to permit its use in the home health care (self-testing) environments.

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Abstract

Dispositif à usages multiples permettant de prélever, collecter, récupérer et stocker des échantillons de fluides, et comprenant un tube de récupération d'échantillons (12), un milieu absorbant les fluides qui comporte un composant en matériau cellulaire (16), et un bouchon (14) qui est physiquement couplé à l'élément absorbant les fluides et conçu pour maintenir celui-ci enfermé de façon étanche à l'intérieur du tube de récupération. Le tube de récupération de ce dispositif à usages multiples comprend un élément tubulaire (12) souple, transparent de préférence, possédant une extrémité ouverte et une extrémité fermée. L'extrémité ouverte comporte un système qui entre en contact étanche avec l'extrémité ouverte d'un bouchon (14). Dans les modes de réalisation préférés, le bouchon a une structure composite et comporte, au niveau de son extrémité fermée, un évent ou canal à fluide (11) destiné à laisser entrer un liquide ou un gaz dans le tube de récupération tout en empêchant, dans les conditions ambiantes, la sortie de fluide.
PCT/US1996/016075 1995-10-02 1996-10-01 Dispositif pour collecter, recuperer et distribuer des echantillons de salive WO1997012681A1 (fr)

Priority Applications (3)

Application Number Priority Date Filing Date Title
AU73946/96A AU7394696A (en) 1995-10-02 1996-10-01 Sample collection, recovery and dispensing device for saliva
PCT/US1997/012880 WO1998014276A1 (fr) 1996-10-01 1997-07-23 Dispositif de prelevement, de distribution et de conservation d'echantillons
AU39623/97A AU3962397A (en) 1996-10-01 1997-07-23 Sample collection, dispensing and retention device

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US53751995A 1995-10-02 1995-10-02
US08/537,519 1995-10-02

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