Patent Grant
10871428
The present disclosure relates to collection and separation of biological fluids. More particularly the disclosure relates to fluid sample collection devices used for collection and separation of fluids such as blood.
Biological samples are frequently used in laboratory and clinical settings to analyze various components in the samples. The biological samples include blood samples, sputum samples, and urine samples. Such samples, for example, are used to determine the levels or concentrations of various components such as HDL, LDL, Cholesterol, hemoglobin, detection of genes using DNA or RNA along with detection of HIV antibodies, or concentrations of drugs.
The biological sample is frequently processed in a liquid form. Accordingly, the liquid sample is collected, handled by the collection facility, transported to a laboratory, and stored pending processing. Activities surrounding a liquid blood sample present various problems including the risk of container breakage or leakage which causes loss of sample and the danger of infection, sample instability during shipment and storage, transport carrier restrictions related to transport of liquid biohazard materials, and collection of significantly more sample than is necessary for testing so as to ensure sufficient sample quantity is available for common methods of serum or plasma preparation and subsequent analysis. Thus, collection of several vials of fluid such as blood from a patient is not uncommon.
In response to the shortcomings of liquid sample collection, transport, and processing, various dried sample devices and methods have emerged. In dried sample devices, a biological sample is collected in the form of a drop or two of fluid such as whole blood. The blood is collected on filter paper and allowed to dry prior to leaving the collection facility. One benefit of using dried blood samples is that dried blood samples are not classified as a special shipping required biohazard material and may be transported through the mail system or other common delivery service just as any other package.
Additionally, even when a blood or other fluid sample is removed from the body, the concentration of various components within the sample can change over time due to various ongoing reactions. For example, biochemical and cellular changes, such as red blood cells metabolizing plasma glucose for continued cellular respiration, continue in liquid samples. Additionally, when using dried whole blood collection methods, such as collection on Whatman 903 filter paper, as the blood dries, the red cells hemolyze which then becomes mixed with red blood cell membrane cholesterol. The red blood cell membrane cholesterol, which is not normally in the serum portion of the blood, then becomes mixed in with serum cholesterol. Such a mixing may yield a clinically significant increase in a patient cholesterol result. Dried fluid samples have the advantage of reducing various reactions, thereby preserving certain components for later analysis.
The transportation and handling of dried fluid samples is thus a significant improvement over transportation and handling of liquid samples. Merely drying a fluid sample does not always ensure the usefulness of the sample. By way of example, in order to perform analysis of certain dissolved blood components a whole blood sample cannot be used. For example, hemoglobin can interfere with serum analytes at the light absorbance in the instrumental step of clinical analyte testing. Accordingly, the red blood cells must first be separated from the blood plasma or serum prior to drying. The most conventional manner of separating serum or plasma from blood cells is by centrifugation. Centrifugation, of course, requires more than a few drops of blood. Additionally, expensive and space consuming equipment must be maintained at the collection site to perform centrifugation.
Various approaches have been developed to provide for separation of blood samples prior to drying of the samples. For example, U.S. Pat. No. 5,064,541, issued to Jeng et al. on Nov. 12, 1991, describes a device which separates plasma from red blood cells that uses an agglutination agent in a filter to clump red blood cells together. The incorporation of an additional biochemical filter in the device adds to the complexity and cost of the device. Additionally, the amount of blood collected may overwhelm the ability of the red blood cell agglutinating agent to work on all of the red blood cells applied in the whole blood sample.
U.S. Pat. No. 4,816,224, issued to Vogel, et al. on Mar. 28, 1989, describes a series of wicking papers and a relative large sample holder with different embodiments that contain many different components. The device is complex and requires significant foot print space when shipping or undergoing sample extraction at a remote laboratory.
U.S. Pat. No. 6,258,045, issued to Ray et al. on Jul. 10, 2001, describes a device which requires tubing for capillary collection of whole blood along with filtration and multiple layers of reactive or non-reactive materials for plasma separation and testing. Capillary collection tubes require a certain level of operator experience and inflict additional pain on the patient when compared to a simple lancet stick. Additionally, the glass tube can be broken or become detached.
Traditional devices for obtaining dried fluid samples further incorporate indirect methods for ensuring that the proper amount of fluid has been collected to allow the desired separation. Some devices incorporate an indicator which changes color or a portion of the strip which provides a chemical reaction. Such devices do not provide an indication of whether or not too large a sample of fluid has been collected.
Therefore, a collecting device that is self-contained and can be used to provide stable dried biological components to a laboratory would be beneficial. Further benefits would be realized if the device is simple to manufacture and provides accurate results. Further benefits would be provided by a device which enables both the sample collector and laboratory personal to visually directly observe the amount of fluids, such as serum or plasma or red blood cells, which have been collected. A device that can be used to separate fluids such as blood into separate components and which is easy to mail without additional charges would also be beneficial.
The present disclosure is directed to assembling a device for separating and drying a fluid sample. In one embodiment, a method of assembling a fluid sample collection card assembly includes forming a tray assembly by supporting an absorbent layer configured to receive a fluid sample on a base portion, the base portion including a tray portion, by positioning the absorbent layer on an upper surface of a holder portion of the tray portion, the holder portion located beneath an upper surface of the tray portion, removably inserting the formed tray assembly into a tray assembly receiving cavity of a case through a mouth portion of the case, and closing, at least substantially, the mouth portion of the case with a faceplate portion of the base portion.
In one or more embodiments, forming the tray assembly further includes securing the absorbent layer configured to receive a fluid sample to the upper surface of the holder portion with an insert.
In one or more embodiments securing the absorbent layer configured to receive a fluid sample to the upper surface of the holder portion with the insert includes frictionally engaging the holder with the insert.
In one or more embodiments, assembling a device for separating and drying a fluid sample includes providing a bridge in the insert, the bridge stiffening the insert to provide increased frictional engagement between the holder and the insert when frictionally engaging the holder with the insert.
In one or more embodiments, providing the bridge includes defining, at least in part, a sample window with the bridge.
In one or more embodiments, defining, at least in part, the sample window with the bridge includes defining the sample window at a location whereat when the absorbent layer is secured to the upper surface of the holder portion, the sample window is located directly above a sample receiving portion of the absorbent layer which is positioned on a non-absorbent ledge of the base portion.
In one or more embodiments, assembling a device for separating and drying a fluid sample includes defining, at least in part, a portion of a viewing window.
In one or more embodiments, supporting the absorbent layer configured to receive a fluid sample on the base portion further includes positioning the absorbent layer configured to receive a fluid sample on a lip of the holder portion, the lip defining an opening in the base portion.
In one or more embodiments, removably inserting the formed tray assembly into a tray assembly receiving cavity of a case includes removably inserting the formed tray assembly into a tray assembly receiving cavity of a case including at least one ventilation hole extending from the tray assembly receiving cavity to an outer surface of the case.
In one or more embodiments, removably inserting the formed tray assembly into the tray assembly receiving cavity includes guiding opposing sides of the tray portion at least one pair of rails extending along the tray assembly receiving cavity.
In one or more embodiments, closing, at least substantially, the mouth portion of the case with the faceplate portion of the base portion includes abutting a portion of the case with the faceplate portion when the tray portion is received within the tray assembly receiving cavity.
These and other advantages and features of the present disclosure may be discerned from reviewing the accompanying drawings and the detailed description of the preferred embodiment of the disclosure.
The present disclosure may take form in various system and method components and arrangement of system and method components. The drawings are only for purposes of illustrating exemplary embodiments and are not to be construed as limiting the disclosure.
Referring to
The opposed grooves 120 and 122 are sized and positioned to receive the tray assembly 104 shown in further detail in
In the embodiment of
The insert 134 includes an outer frame portion 162 and a bridge 164 which extends between opposite sides of the frame portion 162. The frame portion 162 and the bridge 164 define a sample window 166 and a viewing window 168. The insert 134 in some embodiments is formed from a polymer or other nonabsorbent material.
The tray portion 140 in one embodiment is fabricated from a polymer or other nonabsorbent material. In some embodiments, the ledge 150 includes a well or depression (not shown) into which excess fluid sample pools until absorbed by the absorbent layer 132. In other embodiments, the ledge 150 is omitted and the opening 146 extends to a location adjacent to the faceplate 142.
In some embodiments, including embodiments wherein the ledge 150 is constructed of an absorbent material, a non-absorbent material is used to line the ledge 150. The non-absorbent material in some embodiments is Mylar, which is used for its imperviousness to liquid penetration. Other materials which may be used to form an acceptable liquid barrier include thin sheets of Polyethylene, porous UHMWPE film, FEP film, polyester treated sheeting and polypropylene.
Another material which provides an acceptable liquid barrier is porous ePTF film, commercially available from DeWal Industries, Inc. of Saunderstown, R.I. as product number D/W 233MS. The ePTF material is a fluoropolymer material which contains a fluorocarbon material at its surface. The fluorine molecule is the most electronegative element, thereby providing a desired hydrophobic quality. Specifically, it is believed that the fluorocarbon additive to the base plastic polymer in this material and other fluoropolymers enhances the separation of plasma from the red blood cells in the touching absorbent layer 132.
The tray assembly 104 is assembled by inserting the absorbent layer 132 into the holder portion 144 of the base portion 130 on top of the lip 148 (see
Additionally, the characteristics of the absorbent layer 132 may be modified by incorporating designs that utilize other physical forces that affect the flow of substances through the absorbent layer 132. Such physical forces include hydrophobic or hydrophilic interactions as well as ionic interactions. Additionally, temporary hydrogen bonding interactions and gravitational effects may be used to augment or retard flow to provide the desired separation or alteration of a separation of the flowing liquids and suspended cells or other solid materials.
The insert 134 is then positioned within the holder portion 144 on top of the absorbent layer 132. The insert 134 is sized to be at least slightly longer and wider than the holder portion 140. Accordingly, as the insert 134 is positioned within the holder portion 140, the insert 134 frictionally engages the walls of the holder portion 144 trapping the absorbent layer against the lip 148. As shown most clearly in
Amongst other functions, the bridge 164 provides additional stiffness, thereby providing for increased friction. Accordingly, in some embodiments, additional bridges are provided to provide additional stiffness. In some embodiments, the bridges are used in place of the reference marks 152, 154, and 156.
In some embodiments, the bridge 164 is omitted. For example, the bridge 164 may be omitted in embodiments where the material used to construct the insert 134 is sufficiently stiff to provide the desired friction al hold or in embodiments where the insert 134 is sonically welded or otherwise attached to the holder portion 144.
Once the absorbent layer 132 is secured on the tray portion 140, the tray assembly 104 is positioned in the case 102 by aligning the tray portion 140 with the grooves 120/122. The tray assembly 104 is then pushed through the mouth 114 and into the tray assembly receiving cavity 124 until the faceplate 142 substantially closes the mouth 114.
In some embodiments, a small stand-off is established between the faceplate 142 and the case 102 to provide for ventilation of the tray assembly receiving cavity 124. The standoff may be accomplished by providing a protuberance on either the case 102 or the faceplate 142. In the embodiment of
The assembled separator card assembly 100 may be further packaged for storage until a fluid sample is needed. A fluid sample may be obtained in a clinical or laboratory setting. Alternatively, the separator card 100 may be used by lay persons at virtually any location. When a sample is to be collected, a user at least partially removes the tray assembly 104 from the case 102. Removal of the tray assembly 104 is facilitated in the embodiment of
The tray assembly 104 is moved outwardly at least until the sample window 166 is exposed. A sample is obtained by producing the fluid, such as by pricking a finger to obtain blood. Four to five drops of blood or other fluid is then dripped onto the absorbent layer 132 through the sample window 166 such that the fluid sample contacts the absorbent layer 132. In embodiments which do not include a bridge 164 defining a sample receiving portion of the absorbent layer 132, the sample receiving portion of the absorbent layer 132 is indicated in another manner such as by marking on the absorbent layer 132 or by a mark on the insert 134 or upper surface of the tray portion 140.
When the fluid sample contacts the absorbent layer 132, the sample is wicked by the absorbent layer 132, and preferentially aided in movement and separation by the chemical or physical nature of the ledge 150, into the portion of the absorbent layer 132 viewable through the viewing window 168. As additional fluid is placed into the portion of the absorbent layer 132 accessible through the sample window 166, the wicked fluid will become visible through the viewing window 168.
In embodiments simply requiring 4 to 5 drops of blood, the reference marks 152, 154, and 156 may be omitted, and collection of fluid terminated once the requisite number of drops has been provided. In other embodiments, the reference marks 152, 154, and 156 are used to indicate when a sufficient amount of fluid has been provided.
Specifically, once the fluid reaches the reference line 152 as fluid is continuing to be provided to the sample portion of the absorbent layer 132, sufficient fluid has been absorbed to perform a single test on the separated portion of the fluid. Thus, in the case of blood, plasma will be wicked along the absorbent layer 132. When the plasma reaches the reference line 152, provision of blood is terminated if a single test is to be performed. The plasma will continue to wick beyond the reference line, thereby providing sufficient plasma for conducting a single test.
The reference lines 154 and 156 may be provided to indicate when sufficient blood or other fluid has been absorbed to separate a quantity of plasma or other fluid component necessary for performance of two tests and three tests, respectively.
The amount of fluid that is necessary to obtain the desired amount of fluid component will vary based not only on the materials used, but also based upon the geometry of the channel formed. By way of example, using materials identified above absorbent layers may be formed with a width of from about 0.6 centimeters to about 4 centimeters when separating plasma from a blood sample. Optimum separation of plasma, however, is obtained with a width of about 1 centimeter. By optimizing the separation of the plasma, less blood is needed to obtain a particular amount of plasma.
The length of the absorbent layer 132 is also a consideration in ensuring sufficient separation of a sample fluid. By way of example, as the volume of sample fluid deposited in the absorbent layer 132 increases, the red blood cells, in the case of blood, will travel further along the absorbent layer 132. Thus, to ensure that a sufficient separation of a sample fluid occurs in the event too much sample is provided, the length of the absorbent layer 132 may be increased.
Once the desired sample has been collected, the absorbent layer 132 is left to dry. If desired, the tray assembly 104 may be reinserted into the case 102 in the manner described above while the absorbent layer 132 is still damp. The ventilation holes 106/108 which extend from the tray assembly receiving cavity 124 to the atmosphere outside of the case 102 assist with drying. Preferably the ventilation holes 106/108 are positioned such that if an object is inserted through the ventilation holes 106/108, the object will contact the tray portion 140 and not the absorbent layer 132. For example, as depicted in
The separator card assembly 100 may then be shipped via any desired mode of transportation to a processing facility. The dried fluid sample contained in the absorbent layer 132 may be stored for a relatively long time without undue degradation of the sample. Nonetheless, the shelf life of the sample may be extended by placement of the separator card assembly 100 in a storage container such as the package 180 shown in
The package 180 is a gas impermeable package such as a plastic or foil package. The package 180 includes a resealable opening 182. The resealable opening 182 may include a tamper proof mechanism to provide an indication that the package 180 has been opened after a sample has been sealed therein. The package 180 is sized to accept the separator card assembly 100 therein, and may be further dimensioned to allow for insertion into a flat envelope of standard size for automated processing by a postal facility. Alternatively, the package 180 may include a preprinted address 184 and prepaid postage 186 as in the embodiment of
In one embodiment, an oxygen scrubber (not shown) is provided with the package 180. An oxygen scrubber typically includes thin shavings including pieces of metal and a carrier desiccant that loosely holds some amount of water. When the package 180 is sealed with an oxygen scrubber therein, oxygen present within the package 180 reacts with the metal in the presence of water to form rust, thereby binding the oxygen. Elimination of oxygen from the atmosphere of the package 180 provides increased stability for various components within the dried fluid sample. For example, lipid analytes such as HDL, cholesterol, and triglycerides may be further stabilized by removal of oxygen from the atmosphere in which the sample is stored.
If desired, the separator card assembly 100 may be placed within the package 180 and the package 180 sealed before a fluid sample within the absorbent layer 132 has been dried. Sealing the package 180 with a wet fluid sample held in the separator card assembly 100 inhibits drying of the sample.
Removal of at least a portion of the absorbent layer 132 from the tray assembly 104 for further processing is facilitated by the opening 146. One device that may be used to remove at least a portion of the absorbent layer 132 is the removal tool 190 shown in
Accordingly, removal of the portion of the absorbent layer 132 including the separated sample is accomplished by removing the tray assembly 104 from the case 102 as described above and placing the tray assembly 104 on the removal tool 190. Correct placement of the tray assembly 104 on the removal tool 190 may be guided by the guide stop 194. Alternatively, the viewing window 168 and opening 146 are simply positioned over the shaped cutting edge 200. Thereafter, movement of the lever arm 192 in the direction of the arrow 202 forces the protuberance (not shown) on the upper mandrel 196 against the absorbent layer 132 at a location aligned with the viewing window 168 and opening 146. The portion of the absorbent layer 132 viewable through the viewing window 168 is thus forced against the shaped cutting edge 200 which separates the portion of the absorbent layer 132 including the separated sample from the tray assembly 104.
Various other modifications of the separator card assembly 100 may be incorporated to optimize the separator card for particular tests. In one embodiment, polyhexamethylene biguanide hydrochloride (PHMB) is incorporated into the absorbent layer 104. PHMB is an additive used in bandages for inhibiting the growth of microbial organisms such as bacteria and fungi.
In a further embodiment, prior to blood or other biological fluid application, a polypeptide fraction of highly purified dermal collagen of porcine origin (Prionex from Pentapharm) is applied and dried to the separator card absorbent layer 104. A separator card 100 treated with Prionex applied to the absorbent layer 104 at a 0.1 percent concentration can yield close to double the separation area of serum or plasma for a given volume of blood applied to the absorbent layer 104. Other substances such as various proteins, detergents, salts or solvents, or other chemicals may also be used to enhance separation of a sample fluid.
Another additive that is useful when obtaining fluid samples in the form of blood is sucrose. In particular, cholesterol containing molecules and cholesterol itself are hydrophobic molecules which in pure form do not mix with an aqueous solution. The complex arrangement of proteins, salts and carbohydrate and complex carbohydrate in blood, however, holds these hydrophobic molecules in suspension. Disruption of these serum components during drying could result in clumping or aggregation of the hydrophobic molecules rendering successful hydration of the hydrophobic molecules problematic.
Application of sucrose in 1 to 10% wt./vol. concentration followed by drying to the absorbent layer 104, however, provides a more reproducible drying and rehydration of cholesterol containing molecules such as HDL, LDL and the cholesterol molecule itself. It is believed that the carbohydrate sucrose molecules are surrounded by water molecules when a fluid sample is added. Thus, the sucrose layers surround the hydrophobic cholesterol or triglyceride molecules during the drying and inhibit aggregation via hydrophobic binding of the sucrose shielded hydrophobic molecules.
While the present disclosure has been illustrated by the description of exemplary processes and system components, and while the various processes and components have been described in considerable detail, applicant does not intend to restrict or in any limit the scope of the appended claims to such detail. Additional advantages and modifications will also readily appear to those skilled in the art. The disclosure in its broadest aspects is therefore not limited to the specific details, implementations, or illustrative examples shown and described. Accordingly, departures may be made from such details without departing from the spirit or scope of applicant's general inventive concept.
This application is divisional application of application Ser. No. 13/921,934 filed Jun. 19, 2013, which issued as U.S. Pat. No. 10,088,397 on Oct. 2, 2018, the entire contents of which are incorporated by reference herein in their entirety.
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| Number | Date | Country | |
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| Number | Date | Country | |
|---|---|---|---|
| Parent | 13921934 | Jun 2013 | US |
| Child | 16148213 | US |
