MXPA98003232A - Specimen collector, vacuum, with additive acu - Google Patents

Abstract

The present invention relates to a unit for the collection of a body fluid sample from the body of a person, the unit of the present invention includes a hollow tube defining an axis with an open end and a closed end. The hollow tube defines a chamber within this to receive a sample of a fluid collected from a person. The tube has a resilient closure positioned at the open end to close the chamber and to form a seal capable of maintaining a pressure differential between atmospheric pressure and a pressure that is lower than the atmospheric pressure within the chamber. The chamber contains an aliquot and an aqueous additive to treat the fluid sample. The chamber also includes a matrix formed of a fibrous material having capillary spaces to absorb the aliquot of the aqueous additive and an aliquot of a water immiscible liquid with a density greater than about 1.07 grams per milliliter to encapsulate the aqueous additive absorbed in the matrix . The tube has a normally closed resilient valve placed in the chamber to contain the aqueous additive, the liquid and the matrix between the closed end of the tube and the valve. The valve can be opened by centrifugation when a sample is found in the tube, thereby allowing the lower density fractions of the sample and the aqueous additive to collect over the valve and mix it.

Description

MANUFACTURER TUBE, VACUUM, WITH AQUEOUS ADDITIVE FIELD OF THE INVENTION This invention generally relates to the collection of body fluid samples for analysis. More particularly, the invention relates to vacuum tubes for collecting fluid samples, which have aqueous additives therein for preparing the sample collected for analysis.

BACKGROUND Vacuum tubes for sample collection have generally been in use in the United States for almost 50 years. Initially, as described in the United States Patent no. 2,460,641 of Klienert, the tube for the collection of samples was simply a test tube, made of glass, in which it was made empty, with a resilient plug and was proposed for use in taking blood samples. Doctors or practitioners realized the usefulness of these tubes for taking blood samples, vacuum, (trade name "Vacutainer" and available from Becton, Dickinson and Company Franklin Lakes, NJ) the tubes are now supplied with various additives already in these to prepare the blood sample for a specific test.The vacuum is now also made in the tubes at pressures below atmospheric, selected to provide a preselected volume of blood drawn in. The tubes that are most widely used are those in which the vacuum has been made to provide a volume of blood extraction of approximately four and a half milliliters.A tube with additive that is commonly used is known as a "tube" of coagulation ". According to a widespread convention, these coagulation tubes contain a sufficient amount of buffered citrate in aqueous salt to provide a ratio of about 9: 1 blood to aqueous citrate. The coagulation tubes are usually used to collect blood samples for trials that need it or to adjust the dosage of anticoagulant medications. When freshly drawn blood makes contact with citrate, the cell fraction, that is, red blood cells or erythrocytes, platelets and white cells or leukocytes, precipitate, leaving plasma as the supernatant liquid after the tube is centrifuged . Usually, an aliquot of this plasma is then subjected to treatment with a coagulation agent such as a thromboplastin reagent or the like and the coagulation time is measured. These • determinations of clotting time are known as prothrombin time ("PT") and partial activated thromboplastin time GA.PTT ".) Recently, technicians performing the clinical trials have realized the risks associated with the pathogens that carry blood and manufacturers have begun to supply tubes for the collection of blood from materials less likely to be broken by inadvertent handling than the original glass tubes.The tubes for sample collection, vacuum, are now supplied formed of thermoplastic resins such as polyethylene terephthalate (PET) and similar materials Although these thermoplastic resin tubes have reduced the opportunity to break by inadvertent handling, the use of thermoplastic resin tubes to replace glass tubes gives rise to other problems. found out that some thermoplastic materials are not able to withstand vacuum stress, other materials They are permeable in different degrees to gases such as oxygen, water vapor and the like. When the tube material is permeable to gases, the transmission of oxygen or nitrogen to the tube gives rise to the gradual loss of the vacuum. In the case of tubes for coagulation with citrate and other tubes with aqueous additives, the loss of water vapor through the wall of the tube during the storage period gives rise to changes in the concentration of the aqueous additive. In the case of the coagulation tube, once the concentration of the aqueous saline buffer changes appreciably, the ratio of the blood drawn to the aqueous saline buffer no longer follows the convention of the 9: 1 ratio, making the tube unsatisfactory for its use. The loss of water through the wall of the tube has been shown to be a limiting factor for the storage life of the coagulation tube made with thermoplastic material. The problem of the loss of water through the thermoplastic coagulation tubes has been taken by two currents of commercial suppliers. A supplier, Terumo, Elkton, MD distributes its thermoplastic coagulation tubes in a sealed tub containing approximately 15 tubes. As soon as the tub is sealed, the loss of water through the tubes is controlled, • providing a useful storage life. Once the tub is not sealed, the tubes begin to leak water through the walls of the tube. As a result, practitioners need to use these tubes within a few weeks once the tub is opened. Another supplier, Greiner GmbH, Frickenhausen, Germany, distributes a thermoplastic coagulation tube formed of two separate layers formed independently, one inside the other. In the Greiner tube the inner tube is formed of polypropylene, a material that is substantially not permeable to water vapor, and the outer layer is PET. The two-layer tube provides a satisfactory storage life by limiting the transmission of water vapor, but the manufacture and assembly of the two components in the two-layer tube is inefficient compared to a single layer tube. If a single-layer thermoplastic tube were to be available that would limit the loss of water from the tube additives, thereby providing a storage life similar to that of borosilicate glass tubes with similar additives, it would be a step forward in the art of tubes for the collection of blood samples. A tube like this is described hereinafter.

Compendium A device in which the vacuum has been made, for the collection of a sample of a blood fluid from a body of an individual of the present invention includes a hollow tube that defines an axis with an open end and a closed end. The hollow tube defines a chamber therein to receive a sample of a fluid collected from an individual. It has a reclining closure or plug placed on the open end of the tube to close the chamber and form a seal capable of maintaining a differential pressure between the atmospheric pressure and a pressure lower than the atmospheric pressure inside the chamber. The chamber contains an aliquot of an aqueous additive to treat the fluid sample. The chamber also includes a foramada matrix of a fibrous material having capillary spaces therein to absorb the aliquot of the aqueous additive and an aliquot of an immiscible liquid in water with a specific gravity greater than about 1.07 to encapsulate the aqueous additive absorbed in the water. matrix. The tube has a normally closed resilient valve placed in the chamber to contain the aqueous additive, the liquid and the matrix between the closed end of the tube and the valve. The valve can be opened by centrifugation when there is a sample in the tube thereby allowing the fractions of lower density of the sample and the aqueous additive to collect on the valve and mix. The device of the invention offers the ability to manufacture a tube for sample collection containing the aqueous additive with storage stability comparable to glass tubes containing aqueous additives. The device of the invention substantially reduces the risk of breakage caused by poor inadvertent maneuvers of the glass tubes while offering to the practitioners operation similar to that of the tubes with aqueous additive which are widely used at present. As a result of this description, those who practice clinical trials will now know that the tube described works in the same way for many other systems with suitable aqueous additives for blood or other body fluids samples. The use of aqueous coagulation reagents are proposed to be illustrative and not limiting of the invention.

BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 is a perspective view of the unit for the collection of samples, in which the vacuum has been made, of the invention; The figure is a guide to the different graphic elements that are used in figures 1-4. Figure 2 is an exploded cross-sectional view of the invention of Figure 1 taken along line 2-2; Figure 2a is an enlarged schematic view of a part of the matrix component of the invention of Figures 1 and 2; Figure 3 is a cross-sectional view of the vacuum unit of Figure 1 which is loaded with a fluid sample; Figure 4 is a cross-sectional view of the unit of Figure 1 loaded with a sample while in centrifugation; Figure 5 is a top plan view of the unit of Figure 1 taken along line 5-5; Y Figure 6 is a cross-sectional view of the unit of Figure 5 taken along line 6-6.

DETAILED DESCRIPTION Although this invention is accomplished by the modalities in very different forms, a preferred embodiment of the invention is shown in the drawings and in the present described in detail with the understanding that the present description should be considered as an example of the principles of the invention and is not intended to limit the invention to the illustrated embodiment. The scope of the invention is measured by the appended claims and their equivalents. Referring to Figures 1-6, a unit 10 for taking a sample 20 of a body fluid from a body of an individual of the present invention includes a hollow tube 12- defining an axis A having an open end 14 and a closed end 16 defining a chamber 18 therein to receive the sample 20 of a fluid collected from an individual. The tube 12 has a resilient cap or closure 24 disposed at the open end 14 to close the chamber 18 and to form a seal 26 capable of maintaining a pressure differential between the atmospheric pressure and a pressure less than the atmospheric pressure within the chamber. 18. Preferably, the lid 24 includes a shield 25 to substantially re any tendency of a sample contained in the chamber 18 to splash when the resilient cap 24 is removed to gain access to the sample. Unit 10 includes an aliquot of an aqueous additive 28 for the treatment of the fluid sample. Suitable additives include, but are not limited to, organic acids, organic acid salts, alkali metal salts of alures, organic chelating agents, fluorescent dyes, antibodies, binding agents or any other reagent or combination of reagents that are commonly used for Treat body fluid samples for analysis. The unit 10 also includes a die 30 preferably formed of a fibrous material 32 having capillary spaces 33 therein for absorbing the aqueous additive 28. The tube 10 also has an aliquot of a substantially water-immiscible liquid 34 having a water specific gravity greater than about 1.07 to encapsulate the aqueous additive 28 absorbed in the matrix 30. The unit 10 also includes a normally closed resilient valve 36 disposed in the chamber 18 to contain the aqueous additive, the liquid and the matrix between the closed end 16 and valve 36. Valve 36 can be opened by centrifuging tube 10, as illustrated by way of the "G" in Figure 4 when the sample is in chamber 18 thereby allowing fractions of lower density of the sample and the aqueous additive are collected on the valve 36 and mixed. Preferably, valve 36 includes an area of red thickness 38 with at least one partition 40 that can be opened under centrifugation conditions. The applied centrifugation is preferably greater than about 2,500 RCF (2500 times the acceleration of gravity). In the example where the aqueous additive is buffered with citrate in aqueous saline and the sample is freshly drawn blood, a lower density fraction 42 includes plasma and aqueous citrate. The unit 10 of the invention is suitable for other samples of body fluids and other aqueous additives. The following is an example of the use of the unit of the invention to obtain plasma samples suitable for coagulation studies. In this example, the preferred perfluoro polyether serves to encapsulate the aqueous reagent, substantially reng the transmission of water vapor through the tube 12 which is formed of polyethylene terephthalate. The preferred use of the specific materials for a coagulation tube is proposed as illustrative of an application of the invention and not as limiting the invention to only units for coagulation samples or for tubes formed of PET.

List of materials 1. Water-immiscible liquids (hydrophobic) of high density, suitable 34 with a relatively low vapor pressure at ambient temperatures, with a specific gravity at 20 ° C greater than about 1.07, include, but are not limited to , benzyl benzoate, perfluoro polyethers, poly (methyl-3, 3, 3-trifluoropropylsiloxane), dipropyl benzoate, dimethyl benzoate, dimethyl malonate, phenyl acetate, anis aldehyde and the like. The specific gravity value greater than about 1.07 is selected because the cellular components of the blood have a specific gravity between about 1.05 to 1.07. the preferred material is a non-haemolytic perfluoro polyether with low vapor pressure, the weight of the formula between about 2,000-15,000 units of atomic mass, density at 20 ° C between about 1.85-1.90 g / ml. Suitable perfluropolyethers are available from Ausimont USA, Morristown, NJ (Fomblin); PCR, Inc., Grainesville, FL (Aflunox); and the. Dupont, Wilmington, DE (Krytox). 2. Suitable materials for matrix 30 have a large surface area in relation to their mass, are substantially hydrophilic and include, but are not limited to: fibrous materials such as cotton, short polyester fibers, short glass fibers, fiberglass cloths , short polyamide fibers and cellulosic short fibers and the like; the inert hydrophilic foams such as polyurethanes, polyvinyl alcohol and the like, and cellulosic papers such as filter papers and the like. The preferred material for matrix 30 is short fiberglass strands of 1000-2500 yard? per pound as available from Owens Corning (Vitron) with a filament diameter between approximately 0.00021-0.00028 inches, a bulk density between approximately 300 to approximately 500 grams per kilometer and a nominal length per unit weight of approximately 1500 yards per pound. Short fiberglass strands are preferred for this application because they have a large surface area in relation to their mass, allowing the aqueous saline solution to be dispersed on the surface of the matrix. 3. Physiological saline solution for aqueous additive 28, 0.9'é aqueous sodium chloride with a pH between about 7.0-7.2. 4. Suitable resilient elastomers for the valve include but are not limited to Santoprene 8211-35, 8201-60 or equivalent, Monsanto, St. Louis, MO and the silicone elastomer Silastic, Dow-Corning, Midland, MI or equivalent. The Shore A durometer between about 50 and 100.

. Citric acid monohydrate, reactive grade ACS or equivalent. 6. Sodium oxalate dihydrate, ACS reactive grade or equivalent. 7. Sodium citrate, ACS reactive grade or equivalent. 8. Potassium sorbate ACS reactive grade or equivalent. 9. Ethylene diamine tetraacetic acid disodium (EDTA), reactive grade ACS or equivalent.

. Sodium fluoride, ACS reactive grade or equivalent. 11. Potassium chloride, reactive grade ACS or equivalent. 12. Suitable materials for forming the cylindrical tube with closed end 12 of a suitable thickness and size include, but are not limited to, substantially transparent thermoplastic materials such as polycarbonate, polypropylene, polyethylene terephthalate and the like. For the purposes of these examples the tube 12 is formed of a polyethylene terephthalate (PET) tube with a preferred diameter of 13 mm and with a preferred length of 100 mm, other sizes and other materials may be preferred for other applications. 13. The resilient elastomeric lid 24 is sized to fit the tube and maintain an internal pressure below the atmospheric pressure. Suitable materials include, but are not limited to, silicone rubber, natural rubber, styrene-butadiene rubber (SBR), ethylene-propylene dimer, monomer (EPDM), polychloroprene, and the like. Natural rubber is preferred for lid 24 for the illustrated application. 14. Polypropylene, polyvinyl chloride, polyethylene and the like are suitable thermoplastic materials to form the protection of the plug 25. Polyethylene is preferred for protection in this application. The protection of the cap 25 preferably has an outer size of the skirt extending further and covers a portion of the outer surface of the tube adjacent the open end as the cap is removed from the tube. By extending over and covering the part of the tube, the shield 25 serves to reduce the possibility of the sample splashing when the elastomeric lid 24 is removed from the open end of the tube.

. Purified water, USP or equivalent Example: A. Materials: 13 mm per 100 mm PET tube, resilient plug made of natural rubber, protection of the cap with polyethylene; short fiberglass strands; perfluoro polyether (Fomblin M60); water cushioned sodium citrate 1.29 M, physiological saline, potassium sorbate. B. Assembly: with the tube held upright, an aliquot of 0.25 ml of perfluoro polyether liquid 34 is distributed approximately in the lower part of the tube 12. The fiberglass matrix of approximately 0.5 grams 30 is placed in the tube over the liquid 34. Slowly 0.5 ml of aqueous salt 28 is introduced onto the glass fiber matrix 30 to allow the solution to wet the matrix 30. Approximately 0.75 ml of perfluoro polyether liquid 34 is introduced over the aqueous saline solution 28 and the matrix of fiberglass 30. The elastomeric valve 36 is placed in the tube 12 to substantially contain the glass fiber matrix 30, the aqueous saline solution 28 and the perfluoro polyether liquid 34 against the closed end of the tube. 16. Preferably, the valve 36 is positioned with the area of reduced thickness 38 positioned towards the open end 14 of the tube 12. Preferably, the valve 36 has an outer diameter "Y" larger than an internal diameter "X" of the chamber 18 inside the tube 12. In this way, when the valve 36 is placed inside the tube, the difference in diameters gives rise to an interference fit between the tube and the valve to maintain the valve 36 as it was placed. This position for valve 36 substantially eliminates entrapment of air between the perfluoro polyether liquid 34 and valve 36. Approximately 0.05 ml of 1.29 M aqueous citrate buffer is introduced into the tube above the valve. In this embodiment, the water is substantially evaporated from the citrate buffer leaving a substantially dry residue 29 on the valve 36 that mixes with the sample when it is introduced into the chamber 18. The chamber 18 is subjected to vacuum at a pressure below the atmospheric pressure sufficient to provide a blood extraction of 4.5 ml and the resilient cap 24 is inserted with the cap protection 25 to maintain the pressure differential. C. Use: introduce a blood sample in the conventional unit using a phlebotomy needle 50. Place the unit 10 in a suitable centrifuge and apply between approximately 2,000 to approximately 3,000 RCF to the tube containing the sample as is usually done with the tubes conventional With centrifugation, materials with higher density migrate towards the bottom of the tube and materials with lower density migrate upwards. The effect of these migrations on the tube containing the blood sample is that the cellular components 60 of the blood sample move towards the bottom of the tube through the resilient valve and the aqueous saline solution moves upwards and mixture with blood plasma and citrate. In addition, the higher density perfluoro polyether liquid 34 remains at the closed end of the tube 16 together with the matrix. At the end of the centrifugation, the valve returns to the normally closed position and the blood plasma component, in the conventional ratio of approximately 9: 1 blood to aqueous citrate is in the highest part and, as the lower density fraction, can be removed to perform conventional coagulation studies »To select the liquid with low vapor pressure and high density for use as an encapsulant, the compatibility of the liquid with the liquid must be taken into account. material selected for the tube and for the absorption matrix. The chemical or physical interactions between one of these components can adversely affect the operation of the invention. In addition, the compatibility of the low vapor pressure liquid, of higher density with the specific sample and the tests to be carried out in the sample must be evaluated. If the lower vapor pressure liquid of higher density is carried by the sample, this could adversely affect the results of subsequent tests in the sample. Similar considerations should be made in relation to the interactions between the materials of the matrix and the liquid, the sample and the matrix, the material selected for the valve, the reagents and all the components as well as any of the effects of radiation or other sterilization conditions. Materials selection studies: compatibility was determined between the upper density 34 low vapor pressure liquid with tube materials; with blood samples; and the matrix material. In the compatibility tests carried out for the selection of the preferred embodiment for the liquid 34, it was found that the perfluoro polyether had no unfavorable interactions with PET, nor did it cause hemolysis of the blood [sic]. In the tests with diethyl benzoate, dimethyl malonate, phenyl acetate, anisaldehyde and diethyl malonate for compatibility with PET, all showed some degree of interaction, as demonstrated by the PET tube that became turbid or white. In addition, as illustrated in Figure 2a, it was found that perfluoro polyether is effective in encapsulating the aqueous saline solution and substantially reduces the loss of water through the PET 12 tube. For this application, for example, the benzoate of benzyl for the liquid 34 was not satisfactory because slight hemolysis of the blood samples was observed. Examination of the cotton fibers and the filter paper for the matrix 30 showed that there was insufficient absorption of the aqueous saline solution and the release of the absorbed salt solution was unsatisfactory during the centrifugation. The unit for the fluid collection of the invention functions in the same way for units for the collection of conventional fluids with tubes formed of borosilicate glass. The unit 10 of the invention through the use of the encapsulating liquid 34, the matrix 30 and the valve 36 offers the practitioners of blood collection and analysis the ability to use the thermoplastic tube that is less prone to breakage by inadvertent mishandling while that maintains the expected performance offered by the units for the collection of samples, vacuum, conventional glass.

Claims (1)

CLAIMS 1. A vacuum unit for the collection of a sample of a body fluid from an individual's body that comprises: a hollow tube that defines an existing axis that has an open end and a closed end defining a camera in it to receive a sample of a fluid collected from an individual; A resilient closure disposed at the open end to close the chamber and form a seal capable of maintaining a pressure differential between atmospheric pressure and a pressure less than the atmospheric pressure within this chamber; An aliquot of an aqueous additive for the treatment of the fluid sample; A matrix formed of a fibrous material having capillary spaces therein to absorb the aliquot of the aqueous additive; An aliquot of liquid immiscible in water having a specific gravity greater than about 1.07 to encapsulate the aqueous additive absorbed in the matrix; and A normally closed resilient valve placed in the chamber to contain the aqueous additive, the liquid and the matrix between the closed end and the valve, it being possible to open the valve when the sample is in. - > / ™ p i - * - •, - \ c V? Nn 'n * - «1 -n 1 tm ~! t r 1 - - »« - ^ 4- -n ~ -? i- » r «< "• lili $ 3Q H H approximately 13,000 units of atomic mass. 3. The unit of claim 1, wherein the matrix is selected from the group consisting of short strands of glass, glass wool, cotton fibers, nylon fine fibers and combinations thereof. The unit of claim 3, wherein the matrix is of short glass strands having about 10 μm average diameter, a bulk density of between about 330 grams per kilometer and a nominal yardage of about 1500 yards per pound. The unit of claim 1, wherein the normally closed resilient valve is formed of an elastomeric material selected from the group consisting of natural rubber, synthetic elastomers and thermoset thermoplastic elastomers. The unit of claim 5, wherein the normally closed resilient valve is formed of a thermoplastic elastomer having the shape of a disk with an outer section and a central section, the middle section having a thickness less than the thickness of the external section. The unit of claim 6, wherein the normally closed valve further comprises at least one division of the diameter in the central section, so that when the tube contains the sample and is subjected to centrifugation of the tube at about 2,000 a Approximately 3,000 RCF, the valve allows the aliquot of the additive additive to mix with the sample. The unit of claim 7, wherein the hollow tube has an internal diameter and the valve has an outer diameter greater than the internal diameter and the valve has an outer diameter greater than the inner diameter of the tube thereby offering an adjustment of interference to keep the valve substantially normal to the axis of the chamber. The tube unit of claim 1, wherein the aqueous additive further comprises materials that are selected from the group consisting of citric acid, oxalic acid, salts of citric acid and oxalic acid, sodium chloride, potassium chloride, acid disodic ethylenediamine tetraacetic acid, sodium fluoride and combinations of these. 10. The unit of claim 1 further comprises a portion of a sample modifying reagent disposed in the chamber between the resilient valve and the open top of the tube so that when the sample i is introduced into the chamber, the modifying reagent makes contact with the sample. SUMMARY OF THE INVENTION The present invention relates to a unit for the collection of a sample of body fluid from the body of a person, the unit of the present invention includes a hollow tube that defines an axis with an open end and a closed end. The hollow tube defines a chamber therein to receive a sample of a fluid collected from a person. The tube has a resilient closure positioned at the open end to close the chamber and to form a seal capable of maintaining a pressure differential between atmospheric pressure and a pressure that is lower than the atmospheric pressure within the chamber. The chamber contains an aliquot and an aqueous additive to treat the fluid sample. The chamber also includes a matrix formed of a fibrous material having capillary spaces to absorb the aliquot of the aqueous additive and an aliquot of a water immiscible liquid with a density greater than about

1.07 grams per milliliter to encapsulate the aqueous additive absorbed in the matrix . The tube has a normally closed resilient valve placed in the chamber to contain the aqueous additive, the liquid and the matrix between the closed end of the tube and the valve. The valve can be opened by centrifugation when a sample is found in the tube, thereby allowing the lower density fractions of the sample and the aqueous additive to collect on top of the valve and mix.