Sampling Device

Abstract

Provided herein are systems and methods for collecting biological samples. The sample may be collected using a sample collection device, where the device is configured to prevent oxidation of the sample within the device. The sample collection device may include a component that absorbs oxygen within the device. The sample collection device may be used to preserve the sample for transport. The sample collection device may be used to preserve the sample for later analysis. The sample collection device may include a membrane with one or more test areas for detecting one or more target analytes within the sample.

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of U.S. Provisional Application No. 63 / 368,320, filed July 13, 2022, which is incorporated herein by reference in its entirety.

[0002] Technical Field The present disclosure relates to devices for collecting biological samples. [Background technology]

[0003] Blood used for diagnostic testing is always extracted from a patient with a hypodermic needle and collected in a test tube. The collected blood is then packaged and sent to a remote laboratory where various diagnostic tests are performed. However, the volume required for many diagnostic tests is much smaller than the actual sample collected. Some tests also require the separation of cellular components from the sample.

[0004] Many tests require only a small blood sample, and a finger prick rather than a hypodermic needle can yield enough blood. However, this small amount of blood cannot be easily transported to a remote laboratory. When a testing method is not immediately available upon blood extraction, a convenient and reliable method for collecting, preparing, and storing small amounts of blood remains necessary.

[0005] U.S. Patent Publication US 2014 / 0050620 A1, assigned to Boston Microfluidics, Inc., describes several methods for implementing a portable, easy-to-use device for collecting, stabilizing, and transporting a biological fluid sample to a remote laboratory. The device includes a small, handheld housing that provides a chamber for collecting the fluid sample. Movement of the housing itself and / or a mechanism disposed within the housing initiates collection of a predetermined, metered volume of the fluid sample. The device can also stabilize the collected sample and / or seal the sample in the chamber. Other mechanisms in the device can mix the collected sample with reagents. Summary of the Invention

[0006] Applicant has recognized that systems and methods for collecting biological samples can facilitate analysis of target analytes among individuals and groups of individuals. Applicant has further recognized systems and methods for collecting biological samples from a location remote from analysis while ensuring assay integrity, such as by preventing sample oxidation. An easy-to-use, portable sample collection apparatus can facilitate acquisition of biological samples for analysis of target analytes present in the biological samples.

[0007] A fluid sample collection device according to embodiments disclosed herein includes a housing configured to move from a first position to a second position, a sample collection well for collecting fluid, one or more capillaries arranged to draw fluid from the sample collection well, a membrane, and one or more plungers arranged in line with the capillaries and arranged to dispense fluid from the capillaries onto the membrane when the housing moves from the first position to the second position, wherein the device is configured to prevent oxidation of a sample stored within the device when in the second position.

[0008] Embodiments of the device include the following, alone or in any combination:

[0009] The device may include an oxygen absorber or multiple oxygen absorbers and an optional antioxidant or reducing agent disposed within a housing.

[0010] The oxygen absorber may be contained in a sachet, packet, breathable pouch, or other breathable packaging.

[0011] The oxygen absorber may include silica gel, iron powder, carbon, charcoal, calcium sulfate, calcium chloride, zeolite, a mixture of iron powder and sodium chloride, ascorbate with NaHCO3, oxygen scavenging polymers, ferrous carbonate with a metal halide catalyst, oxygen scavenging packets, pyrogallic acid, oxygen scavenging sachets, or combinations thereof.

[0012] The antioxidant or reducing agent may include L-ascorbic acid, sodium L-ascorbate, calcium L-ascorbate, 6-o-palmitoyl-L-ascorbic acid (ascorbyl palmitate), a naturally derived extract rich in tocopherols, synthetic α-tocopherol, synthetic γ-tocopherol, synthetic δ-tocopherol, propyl gallate (propyl 3,4,5-trihydroxybenzoate), octyl gallate (octyl 3,4,5-trihydroxybenzoate), dodecyl gallate (dodecyl 3,4,5-trihydroxybenzoate), erythorbic acid, sodium erythorbate, butylated hydroxyanisole (BHA), or a combination thereof.

[0013] The housing may include a gasket configured to seal the membrane from the ambient environment when the housing is in the second position. The gasket may be provided on a mating surface between the first portion of the housing and the second portion of the housing. The housing may form a substantially airtight seal defining a sealed space within the housing. The sealed space within the housing may include the membrane. The sealed space may be in contact with the membrane and the oxygen absorbent. The volume of the sealed space may be about 1 mL to about 50 mL or about 1 mL to about 10 mL, and may be 1 mL, 2 mL, 3 mL, 4 mL, 5 mL, 6 mL, 7 mL, 8 mL, 9 mL, or 10 mL.

[0014] The membrane may be a test strip. The membrane may be a lateral flow strip.

[0015] The device may or may not include a desiccant within the housing. The housing may additionally include a dry region adjacent to the membrane. A desiccant tablet may be disposed within the dry region. The desiccant tablet may include a desiccant and an oxygen absorber. The device may additionally include a support structure that holds the desiccant tablet adjacent to the membrane. The support structure may further hold an oxygen absorber. The desiccant tablet may further include an inert layer between the desiccant and the oxygen absorber.

[0016] The membrane may include an oxygen absorber. The membrane may include an oxygen absorbing region including the oxygen absorber. The oxygen absorber may be impregnated into the membrane. The membrane may include an antioxidant or a reducing agent.

[0017] The device may include a reagent, for example, the reagent is configured to prevent oxidation of the sample. One or more capillaries may be coated with the reagent. The reagent may include an oxygen absorber. The reagent may include an antioxidant.

[0018] The device may include an antioxidant coating on the device, on portions of the device that contact the sample, or on components of the device, and on a funnel clip, gasket, capillary, pore plug, port or outlet, or membrane. The antioxidant coating may be applied by dip coating, spray coating, or other means during a plastic injection molding process. The device may include an antioxidant coating on a removable funnel clip configured to prevent accidental actuation of the device and direct the sample into a collection well, capillary tube, sample collection well, or combinations thereof.

[0019] The device may be configured to prevent oxidation of a sample stored within the device, such as storing the sample for subsequent analysis in a subsequent assay. The subsequent assay may include an Essential & Metabolic Fatty Acids Analysis (EMFA), a lipid panel, a fatty acid test, a free fatty acid test, a fatty acid profile, a fatty acid panel, an oxidized low-density lipoprotein (OxLDL) assay, an assay measuring oxidation of components in a blood sample, a complete metabolic panel, a complete blood count, a metabolic panel, a liver panel, a prothrombin time assay, a hemoglobin A1c assay, a thyroid-stimulating hormone assay, or a combination thereof.

[0020] The device may be configured to extend the time that a sample may be stored within the device, such as before analysis in a subsequent assay. The device may be configured to allow a sample to be stored within the device for 5, 7, 10, 14, 15, 20, 21, 25, 28, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, or 90 days while storing the sample for analysis in a subsequent assay.

[0021] Moving the device from the first position to the second position may include forming an airtight seal that defines a volume of air within the device, or includes forming a hermetic seal that defines a volume of air within the device.

[0022] The device may be configured to separate the blood sample into plasma and cellular components, and is configured to prevent oxidation of the plasma and cellular components with an oxygen absorber.

[0023] The oxygen absorber or membrane may contain an antioxidant or reducing agent at a concentration of about 0.5 mg / mL to about 20 mg / mL.

[0024] The device may be configured to collect a biological sample, the device including: a housing having a sample collection well for receiving the biological sample and configured to move from a first position to a second position; a conduit including one or more capillaries and disposed within the housing, the conduit having openings at a first end and a second end, the opening at the first end configured to receive the biological sample from the sample connection collection well; a sample storage chamber disposed within the housing and configured to receive the biological sample from the conduit; and a mechanical actuator, wherein the first position provides an opening to the sample collection well and the second position restricts access to the sample collection well, the mechanical actuator configured to dispense a predetermined amount of the biological sample from the second end of the conduit into the sample storage chamber by mechanical force when the housing moves from the first position to the second position and the second position; and the device includes an airtight seal that defines a constant volume of air within the device when the device is in the second position.

[0025] The mechanical actuator may be further configured to control a plunger disposed within the conduit to dispense the biological sample into the sample storage chamber.

[0026] The housing may include a first portion and a second portion that are slidably engaged with one another and configured to be pressed toward one another to configure the device from a first position to a second position.

[0027] The biological sample may include blood.

[0028] A method of preserving a sample for subsequent analysis according to aspects disclosed herein includes inserting a sample, alone or in any combination, into a sample collection well of the device, including any of the above embodiments; moving the housing from a first position to a second position; forming an airtight seal defining an enclosed space within the housing; and removing oxygen from the enclosed space.

[0029] Embodiments of the method include the following, alone or in any combination:

[0030] Oxygen may be removed from the enclosed space using an oxygen absorber or scavenger. The method may further include removing moisture from the space using a desiccant or the like.

[0031] The method can extend the time a sample may be stored before subsequent analysis, which may include assays such as essential fatty acid and metabolic fatty acid analysis (EMFA), lipid panels, fatty acid tests, free fatty acid tests, fatty acid profiles, fatty acid panels, oxidized low-density lipoprotein (OxLDL) assays, assays measuring oxidation of components in a blood sample, complete metabolic panels, complete blood counts, basic metabolic panels, liver panels, prothrombin time assays, hemoglobin A1c assays, thyroid-stimulating hormone assays, or combinations thereof.

[0032] The oxygen absorber or scavenger may comprise an antioxidant or reducing agent including L-ascorbic acid, sodium L-ascorbate, calcium L-ascorbate, 6-o-palmitoyl-L-ascorbic acid (ascorbyl palmitate), a naturally derived extract rich in tocopherols, synthetic α-tocopherol, synthetic γ-tocopherol, synthetic δ-tocopherol, propyl gallate (propyl 3,4,5-trihydroxybenzoate), octyl gallate (octyl 3,4,5-trihydroxybenzoate), dodecyl gallate (dodecyl 3,4,5-trihydroxybenzoate), erythorbic acid, sodium erythorbate, butylated hydroxyanisole (BHA), or a combination thereof.

[0033] The oxygen absorber may include an antioxidant at a concentration of about 0.5 mg / mL to about 20 mg / mL.

[0034] A kit according to another aspect disclosed herein includes the fluid sampling device described above, including any of the above embodiments, alone or in any combination, airtight packaging, an oxygen absorbing packet, a desiccant, a molecular sieve, or a combination thereof.

[0035] Kit embodiments include the above devices, including the embodiments disclosed above, singly or in any combination. [Brief explanation of the drawings]

[0036] The novel features of the invention are set forth with particularity in the appended claims. The features and advantages of the present invention will be better understood by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the invention are utilized, and the accompanying drawings of which:

[0037] [Figure 1] 1 illustrates a biological sample collection device in an open position, according to some embodiments. [Figure 2] 1 illustrates a biological sample collection device in a closed position according to some embodiments. [Figure 3A] 1 illustrates an exploded view of a biological sample collection device according to some embodiments. [Figure 3B] 1 illustrates an exploded view of a biological sample collection device according to some embodiments. [Figure 4] 1 illustrates a sample medium of a biological sample collection device according to some embodiments. [Figure 5] 1 illustrates a sample medium of a biological sample collection device according to some embodiments. [Figure 6] 1 illustrates a biological sample collection device according to some embodiments. [Figure 7] 1 illustrates components of a biological sample collection device according to some embodiments. [Figure 8] 1 illustrates components of a biological sample collection device according to some embodiments. [Figure 9] 1 illustrates components of a biological sample collection device according to some embodiments. [Figure 10] 1 illustrates components of a biological sample collection device according to some embodiments. [Figure 11] 1 illustrates components of a biological sample collection device according to some embodiments. [Figure 12] 1 illustrates components of a biological sample collection device according to some embodiments. [Figure 13] 1 illustrates components of a biological sample collection device according to some embodiments. [Figure 14] 1 illustrates a biological sample collection device according to some embodiments. [Figure 15] 1 illustrates a biological sample collection device according to some embodiments. [Figure 16] 1 illustrates a biological sample collection device according to some embodiments. [Figure 17A] 1 illustrates the implementation of an oxygen absorber within a biological sample collection device according to some implementations. [Figure 17B] 1 illustrates the implementation of an oxygen absorber within a biological sample collection device according to some implementations. [Figure 17C] 1 illustrates the implementation of an oxygen absorber within a biological sample collection device according to some implementations. [Figure 18A] 10 illustrates the implementation of an optional removable extension of a biological sample collection device according to some implementations. [Figure 18B] 10 illustrates the implementation of an optional removable extension of a biological sample collection device according to some implementations. DETAILED DESCRIPTION OF THE INVENTION

[0038] A sample collection device may be used to collect, meter, and store a bodily fluid sample for subsequent assay. Fluid collected from a patient is first introduced into the device through a sample port, such as by directing a blood drop from a fingertip into a well. In some configurations, a metering capillary tube is then used to extract blood from the sample port, and capillary action deposits the blood onto a storage medium. One or more plungers coupled to the closable housing can further facilitate dispensing of fluid from the metering capillary tube onto the storage medium. The plungers may be attached to one or more movable housing components, such that the plungers are forced through the capillary tube when the housing is moved from an open position to a closed position.

[0039] In some arrangements, the assay region may also be located between the capillary and the membrane so that stored reagents are mixed with the fluid when the housing is moved from the open to the closed position.

[0040] A raised ridge may be provided adjacent the well, which provides a convenient place for the patient to wipe their finger to improve blood flow.

[0041] The housing may also include one or more windows positioned on the housing such that at least a portion of the capillary and / or sample media is visible through the window.

[0042] The first and second housing portions can engage and slide along a central support portion to move the housing from an open position to a closed position, thereby forcing the plunger through the capillary tube. In that configuration, the central support portion can include an opening for an insert member that defines a sample well.

[0043] The sample wells may be defined by an inlay member disposed within the housing. In this case, the inlay may also provide a raised ridge. The inlay typically further includes one or more through-holes, each for holding a respective capillary tube in a predetermined position. The inlay member may also be used to hold at least one capillary tube in alignment with at least one plunger when the housing is moved from the open position to the closed position.

[0044] The inlay member may also include a slot disposed at the outlet of one or more of the capillaries, the slot providing a directed path for blood to flow out of the capillaries and into the storage medium.

[0045] The capillaries and / or the inlay components that provide the sample wells and support the capillaries may also be fully or partially transparent. These design features provide additional visual confirmation that the blood fluid sample has been properly collected and / or stored.

[0046] The plunger can be connected to a tab attachment on the end distal from the capillary tube, and the tab can be positioned adjacent to one of the housing components so that the plunger is forced into the capillary tube when the housing is closed.

[0047] A ratchet mechanism may be located at one end of the backbone to further assist in holding the housing in a closed position during transport, and may engage when the housing is moved from an open position to a closed position. In some embodiments, an access hole is provided at one end of the housing, which is a tool for more easily disengaging the ratchet mechanism and prying open the housing to access the stored blood sample.

[0048] The storage medium may take different forms. For example, the storage medium may be a substrate having a pair of spaced apart engaging tabs therein. The blood sample collection storage medium is then placed on the substrate and sized to fit between the engaging tabs.

[0049] FIG. 1 is an isometric view of an exemplary fluid collection device 100. The device 100 includes a two-part housing 101 that supports and encloses a fluid sample port 102. The housing 101 includes a first housing component 101-A and a second housing component 101-B. In this view, the housing is in an open position with the two housing components 101-A, 101-B spaced apart to provide access to the sample port 102. In this view, a sample collection well 104 and one or more capillaries 105 located adjacent to the sample port 102 are partially visible. A window 150 in the housing allows a user to view the status of one or more portions of the fluid sample as it is collected and / or stored within the device 100.

[0050] In some embodiments (not shown), the device may include a removable cap or pore plug that covers the sampling well and holds the two housing parts apart to prevent accidental activation of the device before a sample has been collected. In embodiments, the cap may include a funnel such as those shown in Figures 17A, 18A, and 18B, described below. In embodiments, the pore plug may include a die-cut filter material molded to cover the sampling well.

[0051] In some embodiments, the sample is a biological sample. In some embodiments, the sample is a fluid biological sample. In some embodiments, the sample is a blood sample.

[0052] Although the embodiments herein refer to the use of the biological sample collection device for collection of blood samples, it should be readily understood that the collection device may be modified or adapted to collect a variety of biological samples, such as saliva, stool, urine, hair, skin tissue, or other samples containing biological material.

[0053] 2 is a similar isometric view of device 100. In this view, a blood sample has been obtained through sample port 102, and two housing parts 101-A and 101-B have been pressed together to place device 100 in a second or closed position, in which the blood collection status can still be observed through window 150.

[0054] Device 100 is typically used to collect a blood sample as follows: Device 100 is initially in the open position, as shown in FIG. 1, to provide access to well 104. A user, such as a patient or a medical professional, then uses a lancet to create a blood sample, such as from a fingertip. A few drops of whole blood are then obtained with a finger positioned near, above, adjacent to, or even in contact with well 104 or other portion of sample port 102 to minimize blood spillage.

[0055] The blood is then ultimately drawn into the remainder of the device 100 in one or more different ways. As described in more detail below with respect to one embodiment, blood first flows and / or is drawn from the well 104 by capillary action through one or more collection capillaries 105 adjacent to the sample port. In this embodiment, three capillaries are shown, although fewer or more capillaries may be implemented. The capillaries may be visually transparent to allow a user to confirm that blood is being properly drawn into the device 100. The capillaries 105 may optionally be pre-coated with a reagent such as heparin and / or EDTA for subsequent stabilization and storage of the sample. The capillaries 105 may also have a known, predetermined volume, in which case the incoming sample is accurately metered. The collection capillaries 105 then direct the metered sample into a medium within the device housing 101.

[0056] The user, who may be the patient or a medical professional, then manually closes device 100 by pressing the two housing parts 101-A, 101-B together, resulting in the housing position shown in Figure 2. As will be explained more fully below, the action associated with closing the housing may then optionally be to further process the sample and enact one or more mechanisms to safely store the sample inside device 100.

[0057] Window 150 may include a transparent piece of material that allows a user to view the status of sample port 102, well 104, and / or collection capillary tube 105. In this manner, it indicates whether a sufficient blood sample has been drawn into device 100 (when housing 101 is in the open position of FIG. 1) or whether a sufficient blood sample has been drawn into the device (when housing 101 is in the closed position as in FIG. 2).

[0058] 3A is a more detailed exploded view of the components of device 100. First housing part 101-A is made up of upper case 201-A-1 and lower case 201-A-2, and second housing part 101-B is made up of upper case 201-B-1 and lower case 201-B-2.

[0059] A skeleton structure 203 supports two housing components 101-A, 101-B. The inner vertical walls of the housing components 201-A, 201-B engage elongated slots or other structures formed in the skeleton 203, allowing at least the second housing component 101-B to slide back and forth along the skeleton to move the housing to an open or closed position. In one arrangement, the first housing component 101-A remains fixed in position on the skeleton 203. However, other embodiments are possible in which the first housing component 101-A slides on the skeleton 203 and the second housing component 101-B remains fixed, or both housing components 101-A, 101-B can slide relative to each other.

[0060] The skeleton 203 also supports other components of the device 100. For example, the skeleton 203 provides a location for the sample collection port 102, which is formed from an inlay piece (also called a capillary support member) 252. A rack of plungers 202 is also supported by the skeleton 203. Three plungers are shown for purposes of illustration and not limitation. The skeleton 203 may further include a ribbed portion 230 that supports desiccant tablets (not shown in FIG. 3 ) for further drying the collected sample. The skeleton 203 may also include tines on its end that provide a ratchet closure mechanism 240 that activates when the two housing pieces 101-A, 101-B are pressed together.

[0061] The capillary tube 204 (designated 105 in other figures) is inserted and held in place by a longitudinal hole (not shown in FIG. 3) formed in the inlay 252. The capillary tube may be formed as a rigid tube of precisely defined volume, in which case the capillary tube also performs a metering function. The capillary tube 204 extracts a defined amount of blood by engaging with the blood in the sampling port 102 by capillary action. The inlay 252 may fit into a hole 221 in the skeleton 203. As will be explained in more detail below, the inlay 252 defines the location of the well 104 into which the patient's blood is introduced.

[0062] The capillary tube 204 may optionally be pre-coated with a reagent, heparin, EDTA, or other substance, including an antioxidant.

[0063] One or more capillaries 204 may also store a predetermined amount of liquid reagent. Such reagent may then be dispensed along with or in parallel with the blood sample when the housing moves from the open (first) position to the closed (second) position. However, other types of reagents may also be present in storage areas within the housing. The storage areas (not shown) may hold a first type of reagent, such as a solid surface or substrate, and a second type, which is a liquid storage chamber, each type disposed in the path of the blood sample collected by device 100.

[0064] In one arrangement, one or more plungers 202 tightly engage the inner diameter of the capillary tube 204, forming a blockage that blocks any excess blood sample while pushing a metered volume of sample to a subsequent downstream processing step.

[0065] The base 206 may also fit into the backbone 203 to provide additional mechanical support for the blood collection member 250. The collection member 250 may be comprised of a sample media (also referred to herein as a membrane) 209, which is supported and / or held in place by other components that aid in handling the sample media 209 when it is removed from the device 101 for laboratory processing. These other portions of the collection member 250 may include the base 206, the top frame 208, the media support 210, and the bottom frame 211. The top frame 208 and the bottom frame 211 may have extensions 222-A, 222-B on their outer ends. The extensions 222 further aid in handling the collection member 250 during and after removal of the collection member 250 from the housing 101.

[0066] The sample medium 209 may be any of various types of plasma separation membranes or filters located at or near the outlet of the capillary tube 105. The sample medium 209 may be, for example, a mixed cellulose ester membrane, such as Pall Vivid Plasma Separation, available from Pall® Corporation. The membrane 209 may also be an LF1 glass fiber membrane (sold by General Electric® Company) or other media designed to receive serum or whole blood and separate it into a blood portion and a plasma portion. Media such as LF1 paper have a fibrous structure that slows the velocity of red blood cells and causes the sample to migrate differently, resulting in gradual separation of the plasma sample as it migrates to the paper. The membrane 209 may optionally be pre-impregnated with heparin, EDTA, sugar, oxygen absorbers, antioxidants, or other stabilizers. LF1 paper, which separates plasma from red blood cells through a fibrous matrix, is preferred in some embodiments because it slows the migration velocity of blood cells. However, other types of separation membranes for liquid or dried blood may also be used.

[0067] Plasma separation may also be achieved through non-membrane microstructures that exclude red blood cells by size. For example, plasma separation can also be achieved or enhanced by selectively binding red blood cells. The binding agent is typically coated onto the membrane or microstructure, but may also be attached within the channels.

[0068] The sample media 209 may also be coated with various chemicals to perform tests, such as assays, on the collected sample. Thus, an immunoassay strip may replace all, part, or all of the sample media 209. When the device 100 is closed, the sample is delivered to the sample pad area on the immunoassay strip. The window 150 may also allow for visual inspection of the color change results of the immunoassay or other test.

[0069] Figure 3B is an exploded view of one such exemplary device 100, similar to Figure 3A. However, the device 100 has both a collection membrane 209 and an immunoassay strip 309. The membrane 209 and strip 309 may be arranged in parallel. The collection membrane 209 may receive and store blood samples from some capillaries, and the immunoassay (or other test) strip 309 may receive and process blood samples from other capillaries.

[0070] Alternatively, the sample may be delivered to an assay region within the housing 101, where the capture molecules are exposed to the sample and bind to analytes. These analytes may then be bound by a conjugate and become detectable. The bound analytes may also alter the optical or electrical properties of the surface to which the analytes are bound, thereby becoming directly detectable.

[0071] It may now be appreciated that the act of closing the housing parts together draws the blood sample from the well 104, is drawn into the capillary tube 105 by both capillary action and mechanical forces, and exits the capillary tube and is deposited onto the sample media 209. In particular, the plunger 202 engages the housing part 201-A, which in turn holds the capillary tube 105 in place within the inlay 252. Thus, when the housing parts are closed together, the plunger 202 is forced into the capillary tube 105, forcing the blood onto the membrane 209.

[0072] In some implementations, the material used to fabricate one or more portions or components of the inlay component 252 may be sufficiently elastic to hold the capillary tube 105 in place while the plunger 202 is forced into the capillary tube 105. The elasticity of the inlay 252 may also be selected to seal and / or prevent at least some blood from flowing around the capillary tube 105 rather than through it.

[0073] The closed housing 101 also creates a small, isolated internal cavity above the sample media 209. Sample drying can be further facilitated with the aid of one or more desiccant tablets (not shown) disposed within the cavity. For example, the desiccant may be supported by the backbone 203 adjacent to where the sample media 209 is located when the housing is in the closed position.

[0074] A ratchet mechanism provided at the distal end of backbone 203 facilitates the housing remaining closed during or after the housing is closed. For example, teeth 240 may act as ratchet palls and engage small holes 245 or other features in the end of housing component 101-A (see FIG. 1 ) as the housing is pushed closed. Teeth 240 may be shaped so that the housing can only be opened by releasing the ratchet palls, e.g., by pinching teeth 240, with a pinching tool that accesses small holes 245 in the side of housing component 101-B. Thus, when device 100 is closed by pressing housing components 101-A and 101-B together, the blood sample remains sealed within device 100, ready for transport to a remote laboratory.

[0075] Figures 4A and 4B are top and side views, respectively, showing one way of mounting the sample media 209 and media support 210. Figure 4C is a top view of the media 209, and Figure 4D is a top view of the support 210.

[0076] The media 209 may be a generally rectangular thin sheet or film, paper, or fabric that slides under or fits within the tabs 401, 402. The tabs 401, 402 may be cut into or formed as an opening in the support 410 to hold the media 209 in place. The support 210 may also have a handle portion 410. The handle 410 may fit over the extensions 222 of the frame components 208, 211. The handle 410 makes it easier to handle the collection media 209 when it is removed from the housing 101. The handle 410 may also have other features, such as a shaped peripheral edge 412, to more securely fit the support 410 (and / or frame components 208, 211) within the housing.

[0077] 5 is a plan view of the collection member 250 after it has been removed from the housing 101 some time after a blood sample has been obtained. Note the blood deposit location 500 that was located adjacent the sample port 102 when the sample was obtained. A first region 501 of the sample media 209 contains filtered red blood cells (RBCs). However, other portions of the blood sample diffuse through the media 209 to form a sample separation region 502 and a purified plasma region 503.

[0078] FIG. 6 is a view of device 100 with both top housing covers 201-A-1, 201-B-1 removed. Here, it can be seen that skeleton 203 not only includes an area that supports inlays 252 that define wells 104, but also includes a plunger support area 611 to the left of well 104, and a sample media area 612. A ribbed portion 614 on the right may support one or more desiccant tablets 630, FIG. 6, above sample media area 612. On the left side, three plungers 202 are shown held in place by a pair of supports 616, 617 in the lower left housing part 201-A-2. Each of the plungers 202 is aligned with a corresponding one of the capillary tubes 204, as described in more detail below.

[0079] 7 shows plunger support area 611 and inlay piece 252 in more detail. The left end of plunger 202 is connected to tab 619 that abuts inner edge 620 of lower housing piece 201-A-2. In this way, plunger 202 is forced into capillary tube 105 when the housing is closed. Note that the right side of plunger 202 is inserted into corresponding holes (not shown in FIG. 7) formed in inlay 252, which align with the entrances to capillary tube 204.

[0080] 8 is a bottom, partial view of a portion of support member 203 with bottom housing covers 201-A-2, 201-B-2 also removed. In this view, collection medium 209 and support 210 have been removed for illustrative purposes. A rib 801 on the left end of support 203 can further assist in guiding plunger 202 into inlay 252. Also, note that a side slot 803 is formed on the right side of inlay 252 adjacent the outlet of capillary tube 105. Slot 803 provides an exit path for collected blood from the capillary tube. One or more ridges 820 adjacent slot 803 can further encourage blood exiting capillary tube 204 to migrate into side slot 803.

[0081] 9 is a partial view of the rear side of inlay 252, similar to FIG. 8, but now with collection member 250 inserted into scaffold 203. Note that the position of collection member 250, including frame 208 (and 211, not shown in FIG. 9), holds collection medium 209 adjacent to the exit path from capillary tube 105 and side slot 803.

[0082] FIG. 10 is an exploded view showing the components of one exemplary implementation of inlay 252 in greater detail.

[0083] FIG. 11 is a cross-sectional view of the inlay 252.

[0084] FIG. 12 illustrates the resilient insert component 1030 of the inlay 252. In this implementation, the inlay 252 includes three components: a well component 1010, a capillary support 1020, and a resilient insert 1030. The well component 1010 and capillary support 1020 may be formed of a rigid, visually clear plastic. The inlay 252 may be assembled by engaging pins 1040 on the well component 1010 with corresponding holes 1050 in the capillary support 1020. The well component 1010 generally serves to define the well 104 as a recess or bowl into which the patient initially introduces the blood sample. A longitudinal hole 1015 in the well component 1010 guides the plunger (not shown in FIG. 10).

[0085] The capillary support 1020 has a longitudinal bore 1060 with a diameter suitable for holding the capillary tubes 105 securely in alignment with the plunger (not shown in FIG. 10). Here, three capillaries 105 are supported by the inlay 252, although a fewer or greater number of capillaries 105 are possible. Although not shown in this figure, the capillary support 1020 also wholly or partially defines a lateral slot 803 at the outlet end of the capillary tubes.

[0086] The insert 1030 is formed of an elastic plastic or rubber. The insert 1030 is disposed between the well component 1010 and the capillary support 1020. The insert 1030 also has several holes 1035 formed therein, allowing a corresponding number of capillaries 105 to be inserted into the holes 1035. The insert 1030, which has a generally rectangular shape, preferably has an upper curved ridge 1210. Note here that the upper ridge on component 1101 provides an edge adjacent to the well that can encourage a patient (or caregiver) to swipe their fingertip to fill the well 1010 with blood. The ridge on component 1101 may be treated, coated, or formed with a hydrophobic material so that blood does not stick to the ridge but is instead directed into the sample well.

[0087] 13 is a perspective view of an alternative implementation of inlay 252, in which inlay 252 is formed of a single-piece resilient material such as injection-molded silicone. This form of inlay 1300 has the same features as the form of inlay 252 shown in FIG. 10, including at least a sample well 1301, finger swipe ridge 130, and side slot 1320.

[0088] FIG. 14 is a view of the skeleton 203 with the housing cover removed, showing one possible location for a tablet-form desiccant 1402. Note that the tablet 1402 is held in place above the sample media 209, such as near the outlet end of the capillary tube (not shown in FIG. 14). While only one tablet-type desiccant 1402 is shown, certainly more than one may be provided. In embodiments, the tablet may further include an oxygen absorber. The tablet may include a drying region and an oxygen-absorbing region. The tablet may further include an inert layer between the desiccant and the oxygen absorber.

[0089] It should also be noted that one corner 1450 of one or more housing components, e.g., housing component 201-B-2, may have a different shape than other corners of other housing components 101. For example, corner 1450 may be chamfered and other corners may be rounded. Corners 1450 that are differently shaped may aid in aligning device 100 with automated handling or processing equipment.

[0090] FIG. 15 is a close-up view of plunger 202 showing that its end 1501 may be ribbed or castellated to further promote blood flow into and through capillary tube 105.

[0091] 16 is a detailed view of one method of further retaining the collection member 250 within the backbone 203 with one or more spring clips 1601. The clips 1601 may engage or press against one end of the media support 210. The clips 1601 may engage with other corresponding features within the backbone 203 or housing component 201-B-2 (not shown). Note that the barcode 1600, or other identifying indicia such as a QR code or reference number, may be printed on the back of the collection member 250 or on a label affixed to the back of the collection member 250.

[0092] In use, device 100 provides a very convenient means for a patient to collect blood by squeezing it onto one of their fingers using a lancet. Commercially available lancets may be used, and the choice of lancet type is generally at the discretion of the user. Once a drop of blood is squeezed onto the finger, the patient scoops the drop into well 104 within sample collection port 102 by sliding their finger along protruding elastic edge 1030. Gravity and surface forces propel the blood drop to the bottom of well 104, where it encounters the opening of collection (metering) capillary 105. From there, the blood is further drawn into collection member 250, which contains sample storage medium 209, and is further encouraged to be forced out of the capillary by the plunger when the two housing parts are closed together.

[0093] The closed device 100 then creates a small, isolated internal cavity that can be rapidly dried with the aid of a tablet-type desiccant contained in an internal pocket. In its current form, LF1 paper, when used as a collection medium, produces spots of red blood cell-free plasma and plasma-depleted whole blood. The structure of LF1 paper slows the velocity of red blood cells, causing the samples to migrate differently, resulting in gradual separation as the plasma sample migrates further into the paper. Plasma is well suited for any quantitative blood test because it excludes red blood cells, which tend to interfere with assays for many analytes.

[0094] Thus, device 100 offers a substantially better opportunity for high-quality quantitative assays compared to standard dried blood spots. Furthermore, infectious disease testing can still be performed on the red blood cell portion of the dried sample—plasma-depleted, but still sufficient to accurately detect infectious agents.

[0095] The device is also an ideal mechanism for storing and transporting blood samples. When the device is closed, the blood sample is sealed inside and nearly sealed off from the outside environment. Once closed by the user, the device uses a ratchet mechanism to lock and ensure it remains closed. The device can only be opened by releasing the ratchet pole with a pinching tool that accesses a small hole 245 in the side of the housing 101.

[0096] The fluid sampling devices disclosed herein may include a housing configurable from an open position to a closed position, a sampling well for collecting fluid, one or more capillaries having a predetermined volume arranged to draw fluid from the sampling well by capillary action, a membrane, one or more plungers arranged in line with the capillaries and arranged to dispense fluid from the capillaries onto the membrane when the housing moves from the open position to the closed position, and a fluid stabilizing agent arranged to engage the fluid as the one or more plungers dispense the fluid onto the membrane.

[0097] The stabilizing agent may be heparin and / or EDTA and may be coated inside at least one capillary tube or coated on the membrane. A removable support member may be disposed within the housing to support the membrane in a predetermined position adjacent to the capillary outlet. The housing may additionally include a dry area adjacent to the membrane. The desiccant may be a tablet, and the structure may hold the tablet-type desiccant adjacent to the membrane. One or more capillaries may be coated with a reagent or may hold a predetermined amount of liquid reagent. The storage membrane may contain the reagent. The membrane may be part or all of a test strip, such as an immunoassay strip. Such a test strip may be aligned with the outlet of one capillary tube. The test strip may be a whole blood collection membrane or some other type of assay adjacent to the whole blood collection membrane. The stored reagent may be mixed with the fluid when the housing is moved from the open position to the closed position. A ridge may be disposed adjacent to the sample well. The ridge may be hydrophobic. The collection member disposed within the housing may further include a recess formed in the collection member to provide a sample well, and a raised ridge formed adjacent the recess and extending along only a portion of the outer edge of the recess. The recess may be circular.

[0098] The fluid sampling device includes a housing configurable from an open position to a closed position; a sampling well disposed within the housing for collecting fluid; one or more capillaries having a predetermined volume disposed to draw fluid from the sampling well by capillary action; a membrane; and one or more plungers disposed in line with the capillaries and disposed to dispense fluid from the capillaries onto the membrane when the housing moves from the open position to the closed position. The sample well is visible and exposed to receive fluid when the housing is in the open position, and the housing at least partially surrounds the sample well when the housing is in the closed position. The fluid sampling device further includes an optically transparent window disposed within the housing, the window allowing at least a portion of the sample well, at least one capillary, and / or the membrane to be viewed when the housing is in the open or closed position. The window may be located adjacent to the capillaries. The capillaries may be visually transparent when the housing is in the open position to visually indicate that a fluid sample is being collected by the device. Also, when the housing is in the closed position, the optically transparent window can indicate whether a sufficient fluid sample has been drawn into the device. The device may include first and second housing portions that engage and are slidable along a central support portion to allow the housing to be moved from the open position to the closed position. The central support portion may include a sample well. In some arrangements, the first housing component includes an optically transparent window positioned to allow one or more capillaries to be visible when the housing is in the closed position. The central support portion may hold the capillaries in fixed alignment with the optically transparent window. In some configurations, the membrane provides one or more sample storage or assay areas.

[0099] The fluid sampling device may include a housing configurable from an open position to a closed position, a sampling well disposed within the housing for collecting fluid, one or more capillaries having a predetermined volume disposed to draw fluid from the sampling well by capillary action, a sample storage membrane, one or more plungers disposed in line with the capillaries and disposed to dispense fluid from the capillaries onto the membrane when the housing moves from the open position to the closed position, and a support member or so-called "inlay" disposed within the housing to hold the at least one capillary in alignment with the at least one plunger when the housing moves from the open position to the closed position. The support member may further include one or more through-holes, each of which engages a respective one of the capillaries. All or a portion of the support member may be formed from a resilient material. The device may be configured such that two or more plungers are connected to tab attachments at the ends distal from the capillaries. The housing may include a first housing portion and a second housing portion, the housing being in an open position when the two housing portions are spaced apart and in a closed position when the two housing portions move adjacent to one another. In certain configurations, a tab attachment is disposed in mechanical communication with the first housing portion such that when the two housing portions move adjacent to one another, the plunger also moves, forcing fluid through the capillaries. The support member may further include slots disposed at the outlets of one or more capillaries. Such slots may be positioned to further direct fluid from the capillaries toward the sample storage membrane. Side flanges may be disposed adjacent to the capillaries and slots to further encourage fluid to pass through the side slots. Each plunger may also further include a circumferential seal. The support member may be visually transparent.

[0100] In some embodiments, a fluid sampling device includes a housing configurable from an open position to a closed position, a sampling well for sampling fluid, one or more capillaries having a predetermined volume and arranged to draw fluid from the sampling well by capillary action, a membrane, one or more plungers arranged in line with the capillaries and arranged to dispense fluid from the capillaries onto the membrane when the housing moves from the open position to the closed position, a removable support member arranged within the housing to provide support for the membrane, and an opening in the housing allowing access to the membrane. A fluid stabilizing agent may be deposited within at least one capillary or on the membrane. The removable support member may include a ratchet mechanism that engages when the housing moves from the open position to the closed position. In such a case, the housing includes one or more access openings adjacent to the ratchet mechanism. Further, the ratchet mechanism may include a pawl releasable by the one or more access openings.

[0101] In some embodiments, the fluid sampling assembly includes a spaced apart base having a pair of engagement tabs therein, and a blood sampling area adjacent to the base and sized to fit between the engagement tabs. The base may be formed of Mylar. In some configurations, the engagement tabs are formed by cutting slots in the base. The membrane may be a strip of LF1 paper, a Pall membrane, a bonded glass fiber filter, or other membrane that separates serum or whole blood into a blood portion and a plasma portion. The membrane may be treated with heparin, EDTA, sugar, or other stabilizing agents. Again, the housing may be reconfigurable from an open position to a closed position, may have a sampling well for collecting fluid, or may include one or more capillaries having a predetermined volume arranged to draw fluid from the sampling well by capillary action, or one or more plungers arranged in line with the capillaries and arranged to dispense fluid from the capillaries onto the membrane when the housing is moved from the open position to the closed position.

[0102] In some embodiments, the sample collection device includes one or more components that prevent oxidation of the sample. In some embodiments, the sample media or storage membrane includes one or more reagents that prevent oxidation of the sample. In some embodiments, the sample collection device includes one or more oxygen absorbers, oxygen scrubbers, or oxygen scavengers. In some embodiments, the one or more reagents that prevent oxidation of the sample include ascorbate, glutathione, ascorbate-glutathione, aloe vera, manganese, copper, iron, sodium chloride, carbon, activated charcoal, sodium bicarbonate, metaphosphate, cysteine, pyrogallol, combinations thereof, and other substances that may prevent oxidation of the sample.

[0103] As shown in FIGS. 17A-17C, in some embodiments, an oxygen absorber 1705 is provided within the body of the sample collection device. In these figures, the housing is shown partially disassembled to show the interior of the housing, and in some embodiments, the oxygen absorber 1705 is held by the skeleton 1703 of the device. In some embodiments, the device includes an oxygen absorber 1705 in addition to a desiccant tablet 1702. In the embodiment shown in FIG. 17A, the oxygen absorber 1705 is contained in a packet or pouch that may be inserted into the skeleton 1703. FIG. 17B shows the desiccant tablet 1702 and oxygen absorber packet inserted into the skeleton 1703. FIG. 17C shows the skeleton 1703 with ridges 1706 configured to hold the oxygen absorber packet above the membrane so that the oxygen absorber packet does not come into contact with the membrane. In some embodiments, a seal, barrier, or coating is provided between the desiccant tablet and the oxygen absorber to prevent chemical interaction between the desiccant tablet and the oxygen absorber. In some embodiments, the desiccant tablet is not provided within the housing, and only the oxygen absorber is provided within the housing. In some embodiments, the device is placed within packaging for shipping, and the oxygen absorber is provided within a packaging component of the device.

[0104] FIG. 17A also shows an optional removable cap, extension, or funnel 1710 that fits adjacent to the sample inlet when the housing is in the first position, where the removable extension provides a larger area for collecting a biological sample compared to the collection area of the sample inlet and is configured to prevent activation of a mechanically actuated fluid controller when fitted adjacent to the sample inlet (see also FIGS. 18A and 18B). The removable extension may further include one or more trenches extending from the top of the extension to the area adjacent to the sample inlet, the trenches being shaped to promote drawing the biological sample by capillary action. The removable extension is removably coupled to the housing such that after sample collection, the sample can be removed from the housing and the housing moved to the second position to enclose the sample. In the illustrated embodiment, the removable extension is a four-sided funnel and may further include rounded edges.

[0105] In some embodiments, an oxygen absorber is provided near the membrane or sample media. In some embodiments, to maximize the effectiveness of the oxygen absorber, the device is sealed to be airtight. In some embodiments, the device creates an airtight seal when the device is in the closed position. In some embodiments, a gasket is provided between the upper and lower cases of the second housing component (e.g., between 201-B1 and 201-B-2) to create an airtight seal. In some embodiments, a gasket is provided between the upper and lower cases of the first housing component (e.g., between 201-A and 201-A-2) to create an airtight seal. In some embodiments, a gasket is provided at a surface between the first and second housing components (e.g., 101-A and 101-B) to create an airtight seal, thereby creating a seal at the mating interference between the first and second housing components when the device is in the closed position. A gasket may be disposed on the inner surface of the top of first housing component 101-A to engage the top surface of sample port 102 and cover sampling well 104 when the housing is in the second position.

[0106] In some embodiments, the oxygen absorber comprises an antioxidant or reducing agent comprising L-ascorbic acid, sodium L-ascorbate, calcium L-ascorbate, 6-o-palmitoyl-L-ascorbic acid (ascorbyl palmitate), a naturally derived extract rich in tocopherols, synthetic α-tocopherol, synthetic γ-tocopherol, synthetic δ-tocopherol, propyl gallate (propyl 3,4,5-trihydroxybenzoate), octyl gallate (octyl 3,4,5-trihydroxybenzoate), dodecyl gallate (dodecyl 3,4,5-trihydroxybenzoate), erythorbic acid, sodium erythorbate, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT) (2,6-di-tert-butyl-p-cresol), or a combination thereof.

[0107] In some embodiments, the oxygen absorber comprises an antioxidant at a concentration of about 0.5 mg / mL to about 20 mg / mL. In some embodiments, the oxygen absorber comprises an antioxidant at a concentration of about 0.5 mg / mL to about 1.5 mg / mL, about 0.5 mg / mL to about 2.5 mg / mL, about 0.5 mg / mL to about 5 mg / mL, about 0.5 mg / mL to about 7.5 mg / mL, about 0.5 mg / mL to about 10 mg / mL, about 0.5 mg / mL to about 20 mg / mL, about 1.5 mg / mL to about 2.5 mg / mL, about 1.5 mg / mL to about 5 mg / mL, about 1.5 mg / mL to about 7.5 mg / mL, about 1.5 mg / mL to about 10 mg / mL, or about 1 mg / mL. In some embodiments, the oxygen absorber comprises an antioxidant at a concentration of about 0.5 mg / mL to about 20 mg / mL, about 2.5 mg / mL to about 5 mg / mL, about 2.5 mg / mL to about 7.5 mg / mL, about 2.5 mg / mL to about 10 mg / mL, about 2.5 mg / mL to about 20 mg / mL, about 5 mg / mL to about 7.5 mg / mL, about 5 mg / mL to about 10 mg / mL, about 5 mg / mL to about 20 mg / mL, about 7.5 mg / mL to about 10 mg / mL, about 7.5 mg / mL to about 20 mg / mL, or about 10 mg / mL to about 20 mg / mL. In some embodiments, the oxygen absorber comprises an antioxidant at a concentration of about 0.5 mg / mL, about 1.5 mg / mL, about 2.5 mg / mL, about 5 mg / mL, about 7.5 mg / mL, about 10 mg / mL, or about 20 mg / mL. In some embodiments, the oxygen absorber comprises an antioxidant at a concentration of at least about 0.5 mg / mL, about 1.5 mg / mL, about 2.5 mg / mL, about 5 mg / mL, about 7.5 mg / mL, or about 10 mg / mL. In some embodiments, the oxygen absorber comprises an antioxidant at a concentration of up to about 1.5 mg / mL, about 2.5 mg / mL, about 5 mg / mL, about 7.5 mg / mL, about 10 mg / mL, or about 20 mg / mL. In some embodiments, the device can reduce the presence of oxygen in the air during drying of the membrane after administration. In some embodiments, the device can improve the oxygen scavenging capacity in the return packaging, remove silica gel and molecular sieves (desiccant), increase the oxygen absorber, include an additional oxygen scrubber adjacent to the membrane, include an antioxidant coating, or combinations thereof.In some embodiments, the antioxidant coating may be applied to a component of the device or a component of the device that contacts blood. In some cases, the antioxidant coating may be applied to a funnel lock clip, a gasket, a capillary tube, a pore plug (e.g., a die-cut filter material), a port or outlet, or a membrane. In some embodiments, the coating may be applied by dip coating, spray coating, or other means during a plastic injection molding process. In some embodiments, the oxygen absorber may be included in a satchel or packet, surrounding the membrane without contacting it, or wrapped around the membrane. In some embodiments, a return kit may be provided with the device including the airtight packaging, the oxygen absorbing packet, and the molecular sieve. In some cases, the antioxidant coating may be included on the membrane.

[0108] In some embodiments, the antioxidant coating comprises an antioxidant or reducing agent comprising L-ascorbic acid, sodium L-ascorbate, calcium L-ascorbate, 6-o-palmitoyl-L-ascorbic acid (ascorbyl palmitate), a naturally derived extract rich in tocopherols, synthetic α-tocopherol, synthetic γ-tocopherol, synthetic δ-tocopherol, propyl gallate (propyl 3,4,5-trihydroxybenzoate), octyl gallate (octyl 3,4,5-trihydroxybenzoate), dodecyl gallate (dodecyl 3,4,5-trihydroxybenzoate), erythorbic acid, sodium erythorbate, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT) (2,6-di-tert-butyl-p-cresol), or a combination thereof.

[0109] In some embodiments, the membrane includes an antioxidant or reducing agent. In some embodiments, the antioxidant or reducing agent is dispensed onto the membrane. In some embodiments, the antioxidant or reducing agent is dispensed onto the membrane to form a coating. In some embodiments, the antioxidant or reducing agent is contained within the membrane. In some embodiments, applying an antioxidant onto the membrane increases analyte stability by about 20-30%. In some embodiments, applying an antioxidant onto the membrane increases analyte recovery by about 60%.

[0110] In some embodiments, the antioxidant solution is dispensed onto the portion of the membrane where the sample will be dispensed. In some embodiments, about 180 microliters (μL) of the antioxidant solution is dispensed onto the portion of the membrane where the sample will be dispensed. In some embodiments, about 90 microliters (μL) of the antioxidant solution is dispensed onto the portion of the membrane where the sample will be dispensed. In some embodiments, the antioxidant solution is dispensed onto the center of the membrane. In some embodiments, about 180 microliters (μL) of the antioxidant solution is dispensed onto the center of the membrane. In some embodiments, the membrane is immersed in the antioxidant solution until it is fully saturated. In some embodiments, the membrane with the antioxidant solution is allowed to dry for at least 1 hour before insertion into the device.

[0111] In some embodiments, the antioxidant solution is dispensed onto the membrane in an amount of about 20 μL to about 250 μL. In some embodiments, the antioxidant solution is dispensed onto the membrane in an amount of about 20 μL to about 50 μL, about 20 μL to about 90 μL, about 20 μL to about 120 μL, about 20 μL to about 150 μL, about 20 μL to about 180 μL, about 20 μL to about 210 μL, about 20 μL to about 250 μL, about 50 μL to about 90 μL, about 50 μL to about 120 μL, about 50 μL to about 150 μL, about 50 μL to about 180 μL, about 50 μL to about 210 μL, about 50 μL to about 250 μL, about 90 μL to about 120 μL, or about 9 μL. The solution is dispensed onto the membrane in an amount of 0 μL to about 150 μL, about 90 μL to about 180 μL, about 90 μL to about 210 μL, about 90 μL to about 250 μL, about 120 μL to about 150 μL, about 120 μL to about 180 μL, about 120 μL to about 210 μL, about 120 μL to about 250 μL, about 150 μL to about 180 μL, about 150 μL to about 210 μL, about 150 μL to about 250 μL, about 180 μL to about 210 μL, about 180 μL to about 250 μL, or about 210 μL to about 250 μL. In some embodiments, the antioxidant solution is dispensed onto the membrane in an amount of about 20 μL, about 50 μL, about 90 μL, about 120 μL, about 150 μL, about 180 μL, about 210 μL, or about 250 μL. In some embodiments, the antioxidant solution is dispensed onto the membrane in an amount of at least about 20 μL, about 50 μL, about 90 μL, about 120 μL, about 150 μL, about 180 μL, or about 210 μL. In some embodiments, the antioxidant solution is dispensed onto the membrane in an amount of at most about 50 μL, about 90 μL, about 120 μL, about 150 μL, about 180 μL, about 210 μL, or about 250 μL.

[0112] In some embodiments, the antioxidant solution comprises an antioxidant dissolved in a solvent. In some embodiments, the solvent is ethanol. In some embodiments, the solvent is 100% ethanol. In some embodiments, the solvent comprises ethanol, butyl carbitol, butyl cellosolve, glycol, glycerol, propyl cellosolve, ethoxy triglycol, diethylene glycol monoethyl ether, or a combination thereof.

[0113] In some embodiments, the antioxidant solution comprises an antioxidant at a concentration of about 0.5 mg / mL to about 20 mg / mL. In some embodiments, the antioxidant solution comprises an antioxidant at a concentration of about 0.5 mg / mL to about 1.5 mg / mL, about 0.5 mg / mL to about 2.5 mg / mL, about 0.5 mg / mL to about 5 mg / mL, about 0.5 mg / mL to about 7.5 mg / mL, about 0.5 mg / mL to about 10 mg / mL, about 0.5 mg / mL to about 20 mg / mL, about 1.5 mg / mL to about 2.5 mg / mL, about 1.5 mg / mL to about 5 mg / mL, about 1.5 mg / mL to about 7.5 mg / mL, about 1.5 mg / mL to about 10 mg / mL, or about The antioxidant solution contains an antioxidant at a concentration of about 1.5 mg / mL to about 20 mg / mL, about 2.5 mg / mL to about 5 mg / mL, about 2.5 mg / mL to about 7.5 mg / mL, about 2.5 mg / mL to about 10 mg / mL, about 2.5 mg / mL to about 20 mg / mL, about 5 mg / mL to about 7.5 mg / mL, about 5 mg / mL to about 10 mg / mL, about 5 mg / mL to about 20 mg / mL, about 7.5 mg / mL to about 10 mg / mL, about 7.5 mg / mL to about 20 mg / mL, or about 10 mg / mL to about 20 mg / mL. In some embodiments, the antioxidant solution contains an antioxidant at a concentration of about 0.5 mg / mL, about 1.5 mg / mL, about 2.5 mg / mL, about 5 mg / mL, about 7.5 mg / mL, about 10 mg / mL, or about 20 mg / mL. In some embodiments, the antioxidant solution comprises an antioxidant at a concentration of at least about 0.5 mg / mL, about 1.5 mg / mL, about 2.5 mg / mL, about 5 mg / mL, about 7.5 mg / mL, or about 10 mg / mL, hi some embodiments, the antioxidant solution comprises an antioxidant at a concentration of up to about 1.5 mg / mL, about 2.5 mg / mL, about 5 mg / mL, about 7.5 mg / mL, about 10 mg / mL, or about 20 mg / mL.

[0114] Embodiments may also include the following.

[0115] The fluid sampling device includes a housing configurable from a first position to a second position, a sampling well for sampling fluid, one or more capillaries arranged to draw fluid from the sampling well, a membrane including a test strip, and one or more plungers arranged in line with the capillaries and arranged to dispense fluid from the capillaries onto the membrane when the housing moves from the first position to the second position, wherein moving the device from the first position to the second position includes forming an airtight seal defining a volume of air within the device, and the device is configured to prevent oxidation of a sample stored within the device.

[0116] The device may include an oxygen absorber or antioxidant disposed within the housing.

[0117] The oxygen absorber may include silica gel, iron powder, carbon, charcoal, calcium sulfate, calcium chloride, zeolite, a mixture of iron powder and sodium chloride, ascorbate with NaHCO3, oxygen scavenging polymers, ferrous carbonate with a metal halide catalyst, oxygen scavenging packets, pyrogallic acid, oxygen scavenging sachets, or combinations thereof.

[0118] The antioxidant may include L-ascorbic acid, sodium L-ascorbate, calcium L-ascorbate, 6-o-palmitoyl-L-ascorbic acid (ascorbyl palmitate), naturally derived extracts rich in tocopherols, synthetic α-tocopherol, synthetic γ-tocopherol, synthetic δ-tocopherol, propyl gallate (propyl 3,4,5-trihydroxybenzoate), octyl gallate (octyl 3,4,5-trihydroxybenzoate), dodecyl gallate (dodecyl 3,4,5-trihydroxybenzoate), erythorbic acid, sodium erythorbate, butylated hydroxyanisole (BHA), or combinations thereof.

[0119] The housing may include a gasket configured to seal the membrane from the ambient environment when the housing is in the second position.

[0120] The housing may form a substantially airtight seal defining an enclosed space within the housing when in the second position.

[0121] The sealed space within the housing may be configured to enclose an air gap in contact with the membrane, oxygen absorber, and optionally, the desiccant.

[0122] The membrane may include an oxygen absorber.

[0123] The housing may additionally include a dry region adjacent the membrane.

[0124] A desiccant tablet may be placed in the drying area.

[0125] The tablet-type desiccant may further contain an oxygen absorber.

[0126] One or more of the capillaries may be coated with a reagent that includes an oxygen absorber or antioxidant configured to prevent oxidation of the sample.

[0127] The membrane may include an oxygen absorbing region that includes an oxygen absorber and optionally an antioxidant.

[0128] The device may be configured to prevent oxidation of a sample stored within the device in order to preserve the sample for subsequent assays, which may include essential fatty acid and metabolic fatty acid analysis (EMFA), a lipid panel, a fatty acid test, a free fatty acid test, a fatty acid profile, a fatty acid panel, an oxidized low-density lipoprotein (OxLDL) assay, an assay measuring oxidation of components in a blood sample, a complete metabolic panel, a complete blood count, a basic metabolic panel, a liver panel, a prothrombin time assay, a hemoglobin A1c assay, a thyroid-stimulating hormone assay, or a combination thereof.

[0129] The device may be configured to separate a blood sample into plasma and cellular components, the device being configured to prevent oxidation of the plasma and cellular components with an oxygen absorber.

[0130] The device may include an antioxidant coating on one of the funnel clip, gasket, capillary, pore plug, port or outlet, or membrane.

[0131] The oxygen absorber may surround the membrane without contacting it or may be wrapped around the membrane.

[0132] A method of preserving a sample for subsequent analysis includes inserting a sample into a sample collection well of the device as described above; moving the housing from a first position to a second position to form an airtight seal within the housing defining an enclosed space; and removing oxygen from the enclosed space, wherein oxygen is removed from the enclosed space using an oxygen absorber or oxygen scavenger.

[0133] The method may further include removing moisture from the space using a desiccant.

[0134] The kit includes a device as described above and an oxygen absorbing packet, a desiccant, a molecular sieve, or a combination thereof contained within an airtight package.

[0135] While preferred embodiments of the present invention have been shown and described herein, it will be apparent to those skilled in the art that such embodiments are provided by way of example only. Numerous variations, changes, and substitutions will occur to those skilled in the art without departing from the invention. Various alternatives to the specific embodiments of the invention described herein may be employed in practicing the invention. It is intended that the following claims define the scope of the invention, and that methods and structures within the scope of these claims and their equivalents be covered thereby.

Claims

1. a housing configured to transition between a first position and a second position, the housing including a skeleton; a sampling well for collecting fluid; one or more capillaries positioned to draw fluid from said sampling well; A membrane and one or more plungers disposed in line with the capillary tube and positioned to dispense fluid from the capillary tube onto the membrane when the housing moves from the first position to the second position; an oxygen absorber secured to a ridge on the skeleton of the housing, the ridge configured to suspend the oxygen absorber and prevent contact between the oxygen absorber and the membrane.

2. A tablet-type desiccant; 10. The device of claim 1, further comprising an inert layer separating the desiccant tablet and the oxygen absorber.

3. The device of claim 1 , wherein at least a portion of the membrane is configured to separate cellular material from the fluid when the fluid is dispensed from the capillary onto the membrane.

4. The device of claim 1 , wherein the capillary is coated with a reagent.

5. The device of claim 1 , wherein the scaffold and the sampling well are integrally formed.

6. The support further includes: one or more inserts configured to receive one or more of said capillaries; a ridge formed on an upper edge of the support and positioned adjacent the sampling well.

7. The device of claim 1 , further comprising a lock configured to lock the housing in the second position and engaged when the housing is transitioned from the first position to the second position.

8. a housing configured to transition between a first position and a second position, the housing including a skeleton; a sampling well for collecting fluid; one or more capillaries positioned to draw fluid from said sampling well; A membrane and one or more plungers disposed in line with the capillary tube and positioned to dispense fluid from the capillary tube onto the membrane when the housing moves from the first position to the second position; an oxygen absorber secured to a ridge on the skeleton of the housing, the ridge configured to suspend the oxygen absorber and prevent contact between the oxygen absorber and the membrane; a funnel removably coupled to the sampling well, the funnel preventing the housing from moving between the first position and the second position when coupled to the sampling well, and the funnel allowing the housing to move between the first position and the second position when uncoupled from the sampling well.

9. 9. The device of claim 8, wherein the funnel includes a plurality of interior walls, each interior wall including at least one groove configured to guide fluid into the sampling well.

10. A tablet-type desiccant; 9. The device of claim 8, further comprising an inert layer separating the desiccant tablet and the oxygen absorber.

11. The device of claim 8 , wherein the capillary is coated with a reagent.

12. The device of claim 8 , wherein the scaffold and the sampling well are integrally formed.

13. The support further includes: one or more inserts configured to receive one or more of said capillaries; a ridge formed on an upper edge of the support and positioned adjacent the sampling well.

14. The device of claim 8 , further comprising a lock configured to lock the housing in the second position and engaged when the housing is transitioned from the first position to the second position.

15. a housing configured to transition between a first position and a second position, A first part; A second part; a skeleton fixed to the first part and the second part, a housing that transitions between the first position and the second position by longitudinal movement of the first and second parts; a sampling well for collecting fluid; one or more capillaries positioned to draw fluid from said sampling well; A membrane and one or more plungers disposed in line with the capillary tube and positioned to dispense fluid from the capillary tube onto the membrane when the housing moves from the first position to the second position; an oxygen absorber secured to a ridge on the skeleton of the housing, the ridge configured to suspend the oxygen absorber and prevent contact between the oxygen absorber and the membrane; a gasket provided on a mating surface of the first part of the housing, the mating surface of the second part of the housing being configured to mate with the gasket in the second position to seal the interior of the housing.

16. A tablet-type desiccant; 16. The device of claim 15, further comprising an inert layer separating the desiccant tablet and the oxygen absorber.

17. 16. The device of claim 15, wherein at least a portion of the membrane is configured to separate cellular material from the fluid when the fluid is dispensed from the capillary onto the membrane.

18. The device of claim 15 , wherein the capillary is coated with a reagent.

19. The device of claim 15 , wherein the scaffold and the sampling well are integrally formed.

20. The support further includes: one or more inserts configured to receive one or more of said capillaries; a ridge formed on an upper edge of the support and positioned adjacent the sampling well.

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