SALIVA SAMPLE COLLECTION SYSTEM

Abstract: Saliva samples are collected for bodily constituent analysis by placing a sponge member (5) into a patient's oral cavity. The sponge member (5) is formed similarly to a pacifier nipple. Saliva is absorbed. The saliva is then expelled from the sponge member (5), either by squeezing or centrifuging. In the case of the latter, the saliva is centrifuged into a collection container (12) which, during the centrifuging, is fluid-tightly connected with a sponge holder section (7). A filter (8) may be placed between the sponge holder section (7) and the collection container (12) to clean the saliva and allow only substances with a molecular weight below a cut-off weight to pass into the container. In the former case, the sponge member (5), after saliva has been absorbed, is placed into a vial-like container (12), which has soft walls. The container (12) may be squeezed to expell the saliva which is collected at the bottom of the container (12). A nipple (18) is then severed either by cutting or twisting off a twist cap (19) to remove the saliva from the container (12).

Description: SALIVA SAMPLE COLLECTION SYSTEM Background of the Invention: Field of the Invention: The invention relates to a system for collecting and storing samples of saliva for body fluid constituent analysis. Description of the Related Art: Saliva testing has recently come to the forefront as a preferred option in body fluid constituent analysis. The collection procedure is non-invasive, and saliva has been found to be a very reliable carrier of analyte indicators. For instance, PKU tests on infants are now regularly done, drug abuse is tested in many circumstances, HIV testing may be relatively reliably performed with saliva, and levels of therapeutic drugs may be ascertained through saliva testing. A recent advance in saliva collection and test preparation is disclosed in U.S. Patent No. 5,103,836 to Goldstein et al. An absorbent pad which is impregnated with a salt of a hypertonic solution is inserted into the mouth and saliva is brushed off from the cavity walls. After having absorbed a sufficient amount of saliva, the pad is removed and stored in a vial for later testing. The test kit is suited for immunoglobulin collection and testing for immunological information in the body fluid. That prior art test provides enough saliva for only a single test, i.e. the saliva is not collected for general, multiple testing. Another saliva collector is disclosed in U.S. Patent No. 5,268,148 to Seymour. A portion of filter paper is exposed so that, when enough saliva is collected, the paper will provide an indication that the collected amount is adequate. The method and apparatus described in U.S. Patent No. 4,774,962 to Hebel et al. allows extracting saliva from the human body in that a sponge member is chewed for a certain amount of time. The method may be acceptable for adult saliva collection. Such a free sponge, however, is essentially unsuitable for infant testing due to the danger of ingestion and it is also not acceptable in view of the proposed utilization thereof in HIV and hepatitis testing. The prior art devices have in common that the collection of saliva sample is rather cumbersome, it exposes the medical worker to dangerous substances, and/or the amount of saliva thus collected is inadequate to perform various tests. Also, none of the prior art devices provide a convenient method and kit for collecting large amount of saliva for body fluid constituent analysis. Finally, saliva collection from very small infants, for instance for PKU testing, is quite difficult and virtually always accompanied by forcing the infant's mouth open during the procedure. Summary of the Invention: It is accordingly an object of the invention to provide a saliva sample collection system, which overcomes the hereinafore-mentioned disadvantages of the heretofore-known devices of this general type and which provides a self- contained collection and test kit as well as a reliable and convenient method of collecting saliva samples for general, multiple testing. The method and collection kit, in one mode and embodiment thereof, further make use of a centrifuge, which is standard equipment in any test lab establishment. Finally, it is an object to provide a fully integrated, sterile package, which allows collecting, filtering, handling and centrifuging without any danger of exposure to the medical worker. With the foregoing and other objects in view there is provided, in accordance with the invention, a method of collecting saliva samples for body fluid analysis. The method comprises the following steps: placing absorptive means into a patient's oral cavity and absorbing saliva into the absorptive means; removing the absorptive means from the patient's oral cavity and placing the absorptive means into fluidic communication with a collection container; In a first mode of the invention, the method is continued with a step of squeezing the saliva from the absorptive means, collecting the squeezed-out saliva at the bottom of the collection container, and then harvesting the saliva from the bottom of the container by opening a fluidic conduit at the bottom and utilizing the thus harvested saliva in a saliva testing method. In a second mode of the invention, the method is continued with a step of centrifuging the absorptive means in fluidic communication with the collection container and driving the saliva out of the absorptive means and into the collection container; and removing the absorptive means from the collection container and testing the saliva driven out of the absorptive means in the centrifuging step. In accordance with a preferred mode of the invention, a filter assembly is placed between the absorptive means and the collection container for molecular weight-selective collecting of saliva in the centrifuging step. With the foregoing and other objects in view, there is also provided, in accordance with the invention, an assembly for collecting saliva for body fluid analysis, comprising: absorptive means for placing into a patient's oral cavity and for absorbing saliva therein; a collection and centrifuging assembly having a cavity formed therein for receiving the absorptive means, the collection and centrifuging assembly including a holder section for receiving and holding therein the absorptive means; a collection section attached to and fluidically communicating with the holder section, the collection section receiving the saliva from the absorptive means when the collection and centrifuging assembly is centrifuged; and cap means for closing off the collection section after the holder section has been removed therefrom, for facilitating storage and shipping of the saliva collected in the collection section during centrifuging. In accordance with another feature of the invention, the assembly includes a filter assembly disposed between the holder section and the collection section for filtering the saliva prior to collection in the collection section. In accordance with an added feature of the invention, the filter assembly includes a substantially annular wall for fluid-tightly connecting between the holder section and the collection section, a wire support permanently attached to the substantially annular wall, and a molecular weight membrane for selectively filtering the saliva of materials with a molecular weight greater than a rating of the molecular weight membrane. In accordance with an additional feature of the invention, the absorptive means include a cap member for placing on the holder section and fluid-tightly sealing a top of the holder section, and a sponge member for absorbing the saliva permanently attached to the cap. The sponge member is preferably formed as a pacifier nipple. In accordance with yet another feature of the invention, the assembly includes a safety flange attached to the cap member for preventing ingestion of the absorptive means when the sponge member is placed into the patient's oral cavity. The collection assembly is quite similar to a pacifier, with the essential difference that the nipple portion is formed of absorptive material, so as to absorb saliva while the nipple placed in the patient's mouth. In accordance with a concomitant feature of the invention, the absorptive means are impregnated with a flavor substance for stimulating a patient's saliva production. Appropriate flavors for stimulating the gland may be lemon, lime, orange, or similar flavors. In accordance with a preferred embodiment of the invention there is provided an alternative system which comprises: O 95/30484 PC17US95/05889 -6- absorptive means for placing into a patient's oral cavity and for absorbing saliva therein; a collection container defining a cavity adapted to receiving the absorptive means, the collection container having resilient walls adapted to collapse towards one another upon being squeezed and to drive the saliva from the absoptive means when the absorptive means is disposed in the collection container. In accordance with another feature of the invention, the walls of the collection container are elastically resilient. In accordance with a final feature of the invention, the collection container further comprises a dispensing end in a vicinity of which the saliva is collected, the dispensing end having a nipple formed thereon through which the saliva is removed from the collection container. Other features which are considered as characteristic for the invention are set forth in the appended claims. Although the invention is illustrated and described herein as embodied in a saliva sample collection system, it is nevertheless not intended to be limited to the details shown, since various modifications and structural changes may be made therein without departing from the spirit of the invention and within the scope and range of equivalents of the claims. The construction of the invention, however, together with additional objects and advantages thereof will be best understood from the following description of the specific embodiment when read in connection with the accompanying drawings. Brief Description of the Drawings: Fig. 1 is a sectional view of a cap and sponge collection assembly according to the invention; Fig. 2 is an exploded, partly broken-away, side-elevational view of a three-component assembly according to the invention; Fig. 3 is a bottom-plan view of a filter insert; Fig. 4 is a side-elevational view of a centrifuge vial, i.e. the bottom component shown in Fig. 2, with a closure cap; Fig. 5 is a view similar to Fig. 2 of an alternative embodiment of the invention; and Fig. 6 is a view similar to Fig. 1 of another alternative embodiment. Description of the Preferred Embodiments: Referring now to the figures of the drawing in detail and first, particularly, to Fig. 1 thereof, there is seen a cap and sponge assembly 1 (the collection component) , which includes a cap 2, an optional handle 3, an optional safety flange 4 and a sponge 5. As will become amply clear in the following, the essential components of the assembly 1 are the cap 2 and the sponge 5. The handle 3 may be provided for easier handling of the assembly 1, and it may be integrally formed on the cap 2 or it may be glued thereon. The safety flange 4 is specifically recommended for infant testing. The safety flange 4 may be removable, and for that purpose it would be spot-welded (spot weld 6) to the cap 2 or provided with a safety ring similar to those found on plastic closures of milk jugs. Generally speaking, the cap and sponge assembly 1 is quite similar to an infant pacifier, and the assembly, and particularly the sponge 5, may be shaped in all possible pacifier shapes. The sponge 5 is permanently locked into the inside of the cap, so as to allow a liquid-tight seal when the cap is placed on the components illustrated in Fig. 2. The sponge 5 is either polypropylene, polyethylene, polyurethane, cellulose, or blends therecf. More specifically, the sponge is formed of water-catalyzed polyurethane and more specifically it is prefer&bly formed of HYPOL, available from Hampshire Chemical Corporation. That material has very high absorption density and excellent tensile strength. Similar materials may be used. Factors to be considered, however, are that the material must be largely inert, it must not easily break so as to prevent any ingestion of solid material, and it must have good absorptive qualities. Additionally, as will become clear from the following description, it should be able to withstand centrifugation and be able to release all or most of the saliva previously collected. After saliva has been absorbed in the sponge 5 (after an exposure time between 20 seconds and 5 minutes in the mouth of the test patient) , the cap and sponge assembly 1 is placed on a sponge holder section 7, in that the sponge 5 is inserted and the cap 2 is securely fastened thereto. A simple friction fit between the sponge holder section 7 and the cap 2 will in most cases suffice. It is also possible, however, to provide the cap 2 and the sponge holder section 7 with mutually meshing threads. The sponge holder section 7 is preferably formed as a polypropylene, polyethylene or styrene cylinder and it is provided with an attachment flange 9 at its bottom. A filter assembly 8 is attached at the flange 9 at the bottom of the sponge holder section 7. The filter assembly is preferably attached by a substantially circumferential ultrasonic weld. The filter 8 and the sponge holder 7, therefore, form a liquid-tight seal. The filter assembly 8 has a molecular weight cut-off membrane 10 supported on a simple wire mesh 11. The membrane 10 may be adjusted to any mesh density. By way of example, a 10,000 MW (molecular weight) membrane may be used for cleaning the saliva. Other mesh sizes are also possible, depending on the specimen requirements. A bottom stub portion of the filter assembly 8 inserts tightly into a centrifuge container 12, i.e. a saliva collection tube 12 or collection container 12. The filter 8 may come attached to the collection tube 12, so as to provide an integrated system of the components 7, 8 and 12. The filter assembly 8 may be attached to the collection tube 12 by means of a ultrasonic spot weld 13, or the like. It is important, in this respect, that the strength of the bond between the filter 8 and the collection tube 12 be smaller than that between the filter 8 and the sponge holder section 7. This ensures that, after centrifugation, the filter assembly 8 (together with the sponge holder 7 and the cap and sponge assembly 1 detaches from the collection tube 12. After separation, then, the collection tube 12 is closed and sealed with a standard threaded cap 14. The preferred dimensions of the assembly according to the invention match those of standard centrifuge equipment. For instance, the cylindrical tubes have an outer diameter of 1/2 inch, the length of the collection tube is 2.125 inches, the length of the filter assembly is 5/16 of an inch and the sponge holder with the attached cap is 1.75 inches. The collection tube 12 is also formed of a polypropylene or a similar material, and it is conical on the bottom. This facilitates sample withdrawal. The threaded cap ensures that the collected sample can be stored and shipped without drying or spilling. A frosted area 15 may be provided on the collection tube 12, so as to allow proper libelling. In a further embodiment, the assembly is provided for a specific test application. In that case, the bottom of the collection tube 12 holds a certain chemical reactant. When the saliva is centrifuged into contact with the reaction chemical, an indication is triggered. That indication may, for instance, be in the form of a colorimetric reaction. For that purpose it is clear that the collection tube 12 is formed of transparent or translucent material, or that a viewing window is provided. General information on saliva testing is available from "Saliva as a Diagnostic Fluid", Malamud and Tabak, Editors; Annals of the New York Academy of Sciences; Vo. 694; Sept. 20, 1993. With reference to Fig. 5, we have also provided a much simplified, yet integrated system for saliva collection and analysis. The embodiment is particularly based on the premise that saliva testing by colorimetry and the like has recently seen a flurry of novel developments which are all hindered by the fact that the prior art systems for collecting the saliva are typically cumbersome and slow, and/or the amount of saliva thus harvested is often not sufficient. The recent call for full disposability of such devices is answered as well with the embodiment of Fig. 5. The nipple 5 of Fig. 5 may also be formed of HYPOL material which is directly glued to a lid 16. The adhesive connection is indicated at 17 and it is preferably formed by a LOCKTITE system (primer, accelerator, adhesive) , a cyano-acrylic medical grade adhesive. The lid 16 is internally threaded so that it can be screwed onto the tube 12. In this embodiment, the tube 12 is formed of thin, i.e. squeezable material. Accordingly, when the sponge 5 is disposed in the tube 12 and the tube 12 is laterally squeezed, the saliva is dr_ven from the sponge 5 and it collects at the bottom of trie tube 12. The bottom of the tube 12 is provided with a nipple 18. The nipple 18 can be severed (e.g. cut off with scissors) and the saliva exits from the nipple and into/onto any desired surface on which the saliva testing (e.g. HIV, Hepatitis, Drug of Abuse, PSA, etc.) may be performed. Instead of requiring a cutting tool, the nipple 18 may be provided with a twist-off cap 19. With reference to Fig. 6, the sponge nipple 5 may be directly molded into the cap 16 without requiring an adhesive layer 17. In such a molding process, the directly molded foam rubber, after being molded, is allowed to vent through a casting hole vent 20. A cap plug 21, which is placed onto the cap 6 after the nipple has been molded into the cap 6, is provided with a vent opening 22 as well. A mold opening 23 in the cap 16 is undercut so as to positively and form-lockingly retain the nipple 5 structure in the cap 16.

Claims: Claims : 1. A method of collecting saliva samples for body fluid analysis, which comprises: placing absorptive means into a patient's oral cavity and absorbing saliva into the absorptive means; removing the absorptive means from the patient's oral cavity and placing the absorptive means into fluidic communication with a collection container; and driving the saliva from the absorptive means and collecting the saliva in the collection container. 2. The method according to claim 1, wherein the step of driving comprises squeezing the collection container for indirectly squeezing the saliva out of the absorptive means and into the collection container. 3. The method according to claim 1, wherein the step of driving comprises centrifuging the absorptive means in fluidic communication with the collection container and driving the saliva out of the absorptive means and into the collection container; and removing the absorptive means from the collection container and testing the saliva driven out of the absorptive means in the centrifuging step. 4. The method according to claim 3, which further comprises placing a filter assembly between the absorptive means and the collection container for molecular weight-selective collecting in the centrifuging step. 5. The method according to claim 1, wherein the step of placing comprises placing absorptive means selected from the group consisting of polyurethane, polyethylene, polypropylene, and cellulose. 6. An assembly for collecting saliva for body fluid analysis, comprising: absorptive means for placing into a patient's oral cavity and for absorbing saliva therein; a collection container defining a cavity adapted to receive said absorptive means, said collection container having resilient walls adapted to collapse towards one another upon being squeezed and to drive the saliva from said absorptive means when said absorptive means is disposed in said collection container. 7. The assembly according to claim 6, wherein said walls of said collection container are elastically resilient. 8. The assembly according to claim 6, wherein said collection container further comprises a dispensing end in a vicinity of which the saliva is collected, said dispensing end having a nipp]e formed thereon through which the saliva is removed from said collection container. 9. The assembly according to claim 6, wherein said absorptive means are formed of a material selected from the groups consisting of polyurethane, polyethylene, polypropylene, and cellulose. 10. The assembly according to claim 6, wherein said absorptive means are formed from water-catalyzed polyurethane. 11. An assembly for collecting saliva for body fluid analysis, comprising: absorptive means for placing into a patient's oral cavity and for absorbing saliva therein; a collection and centrifuging assembly having a cavity formed therein for receiving said absorptive means, said collection and centrifuging assembly including a holder section for receiving and holding therein said absorptive means; a collection section attached to and fluidically communicating with said holder section, said collection section receiving the saliva from said absorptive means when said collection and centrifuging assembly is centrifuged; and cap means for closing off said collection section after said holder section has been removed therefrom, for facilitating storage and shipping of the saliva collected in said collection section during centrifuging. 12. The assembly according to claim 11, including a filter assembly disposed between said holder section and said collection section for filtering the saliva prior to collection in said collection section. 13. The assembly according to claim 12, wherein said filter assembly includes a substantially annular wall for fluid-tightly connecting between said holder section and said collection section, a wire support permanently attached to said substantially annular wall, and a molecular weight membrane for selectively filtering the saliva of materials with a molecular weight greater than a rating of said molecular weight membrane. 14. The assembly according to claim 11, wherein said absorptive means include a cap member for placing on said holder section and fluid-tightly sealing a top of said holder section, and a sponge member for absorbing the saliva permanently attached to said cap. 15. The assembly according to claim 14, wherein said sponge member is formed as a pacifier nipple. 16. The assembly according to claim 15, including a safety flange attached to said cap member for preventing ingestion of said absorptive means when said sponge member is placed into the patient's oral cavity. 17. The assembly according to claim 6, wherein said ab¬ sorptive means are impregnated with a flavor substance for stimulating a patient's saliva production. 18. The assembly according to claim 11, wherein said absorptive means are formed of a material selected from the groups consisting of polyurethane, polyethylene, poly¬ propylene, and cellulose. 19. The assembly according to claim 11, wherein said absorptive means are formed from water-catalyzed poly¬ urethane. 20. The assembly according to claim 6, which further comprises a chemical test reagent disposed in said collection container.

Inventors: D ANGELO JOSEPH P, LEVANDOSKY NICHOLAS, SCHUR HENRY, D'ANGELO, JOSEPH, P., LEVANDOSKY, NICHOLAS, SCHUR, HENRY
Applicants: ANGELO JOSEPH P D, SCHUR HENRY, D'ANGELO, JOSEPH, P., SCHUR, HENRY
Application year: 1995
Main classification: B01L11
IPC codes: A61B10, A61B19, B01L3