A medium having a hydrophobic pattern and a break line that define a blood collection volume

Abstract

The blood sample collection and / or storage device includes a medium, such as a membrane or microstructured environment, for storing a bodily fluid sample, such as a blood sample. The medium has a hydrophobic pattern formed thereon or therein to define precisely sized channels for fluid flow or retention. Break lines in the medium define predetermined areas (or volumes) of the medium. After sample collection, the medium may be split along the break lines to obtain a precisely measured amount of fluid sample.

Description

Technical Field

[0001] Cross - Reference to Related Applications This application claims the benefit of U.S. Provisional Patent Application No. 62 / 896,715, filed on September 6, 2019, and U.S. Provisional Patent Application No. 63 / 060,279, filed on August 3, 2020, both of which are hereby incorporated by reference in their entirety.

Background Art

[0002] This patent relates to the precise collection of body fluids, such as blood samples.

[0003] Background Information Blood used in diagnostic tests is typically drawn from a patient with a hypodermic needle and collected in a test tube. The collected blood is then packaged for transport to a remote laboratory where various diagnostic tests are performed. However, many diagnostic tests require significantly less volume than the actual sample collected. There are also tests that require the separation of cellular components from the sample.

[0004] Many tests require only a small blood sample, where a finger prick rather than a hypodermic needle can produce sufficient blood. There is still a need for a convenient and widely available method to collect and hold a small, accurately measured amount of blood.

Summary of the Invention

[0005] Media such as membranes are used to collect body fluid samples such as blood samples. The membrane has a hydrophobic pattern to define precisely dimensioned channels for fluid flow. A break line in the membrane defines a predetermined area (or volume) of the membrane. After collection and transport, the membrane may be split along the break line to obtain a precisely measured blood sample.

[0006] More specifically, in one embodiment, the device may include a medium such as a membrane or a microstructured environment having channels defined by at least one pattern-processed hydrophobic region. At least one break line intersects the channels to define a predetermined area or collection volume of the medium.

[0007] The break lines can be used to define different areas of the medium that can be easily detached for further processing.

[0008] In some embodiments, two or more break lines may define corresponding multiple areas of the medium. The different areas may be coated with different reagents or may have different sizes or shapes.

[0009] The hydrophobic region or corresponding region may define a fluid path. The path can direct a fluid sample to different areas, or regulate the speed of fluid movement, or promote further saturation of the medium.

[0010] The medium may include multiple layers, some of which may be membranes, and others may include reagents, conjugates, or other substances. Lateral flow It may also be a strip.

[0011] The layers may include hydrophobic or hydrophilic materials to further direct the fluid.

Brief Description of the Drawings

[0012] Figures 1 - 18 are examples of collection media that may include channels defined by hydrophobic regions and / or precise volumes defined by break lines. Specifically, they are as follows.

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DETAILED DESCRIPTION OF THE INVENTION

[0013] This patent application describes membranes, other media such as microstructured environments, which collect and store precisely defined amounts of blood or other fluid samples. Generally, the medium has one or more channels defined by wax or other hydrophobic regions. In some embodiments, the channels can be defined by creating immiscible hydrophobic regions. The hydrophobic regions in the medium can be arranged to prevent liquid from entering a region where there is liquid, either through a physical occlusion region or a similar physical barrier, by hydrophobic forces.

[0014] One or more channels defined by wax or some other hydrophobic region direct fluid while collecting it along a defined path. The hydrophobic regions can be used not only to define the path but also to keep the reagents or layers of the medium in a separated state. Additionally, the hydrophobic regions can be used to properly define a reaction when mixing the sample with the reagent.

[0015] The hydrophobic region may define different types or different shapes of fluid pathways. Pathways having different shapes and lengths, such as a meandering pathway or other serpentine pathway, may be used to regulate and / or slow the speed of fluid movement through or along the medium. Slowing the speed of movement of a fluid sample may then allow the medium to more completely absorb the fluid via the resulting capillary action slowdown.

[0016] In some embodiments, the medium is housed within several different types of device housings that form a sample collection device.

[0017] In some embodiments, the compartment of the medium may be defined by a break line such as a perforation. The compartment may surround a predefined area of the medium and / or may further define one or more flow paths. The break line allows the medium to ultimately be divided into compartments that have collected a predefined volume of fluid.

[0018] The break line may take the form of different shapes. In one embodiment, one or more circularly shaped break lines allow for precise volumes of a dried body fluid sample, such as a blood sample, to be collected from the medium and easily removed. Currently, circular holes are punched into dried blood spot cards and the predefinition of the circles can assist in automation. The break line also allows for easy detachment of the test area from the rest of the device.

[0019] In some embodiments, the break line may allow for detachment of the assay area and the sample area that can then be used for final analysis. In some embodiments, the break line may define or control the flow rate by narrowing the channel. In some embodiments, the areas separated by the break line of the membrane may be treated with different reagents.

[0020] The media may also include a device that provides a microstructured environment. An environment composed of a number of elements, such as fibers, small holes, or pillars, is arranged to create a field that decelerates the flow of specific elements of the fluid, such as red blood cells, white blood cells, or other cellular substances.

[0021] Figure 1 is a plan view of such a media (400). The primary area (401) includes a portion of the membrane through which fluid flows (also referred to herein as channel (401)). That portion of the media (400) through which the fluid flows is exposed and uncoated. The other area (402) is coated with a hydrophobic region such as wax (and as shown by hatching in the drawing). The outer edge of the hydrophobic region provides a boundary (404) that defines a precise area to the fluid channel (401).

[0022] Although only one side of the media (400) is shown, it should be understood that the hydrophobic region may generally coat both sides of the media (400) or extend completely across the membrane (400). In some embodiments, compartments of the media (400), such as channel (401), may also be partially coated with a hydrophobic region to decelerate the flow of fluid through this compartment.

[0023] The media (400) may be a planar sheet-like sample media, such as membranes or filters of various types for plasma separation. For example, a mixed cellulose ester membrane such as Pall Vivid Plasma Separation from Pall (trademark) Corporation may be used. The membrane may also be an LF1 glass fiber membrane (sold by General Electric (trademark) Company) designed to receive lymph fluid or whole blood, or some other media, by which the blood portion and the plasma portion are separated.

[0024] Cell membrane type media (400), such as LF1 paper, cause different migrations of samples at a slower rate for red blood cells, resulting in a fibrous structure such that as the plasma sample travels down the defined channel, a gradual separation of the plasma sample is brought about. LF1 paper, which separates plasma from red blood cells through a fibrous matrix, is preferred in some embodiments as it causes the slow movement of blood cells. However, other types of separation membranes for liquid or dry blood may be used for the media (400). The media (400) can optionally be pre-impregnated with heparin, EDTA, sugars, or other stabilizers.

[0025] Plasma separation may also be achieved through a media that is a non-cell membrane microstructure that excludes red blood cells by size. For example, plasma separation can be achieved or enhanced by selectively binding red blood cells using an agent. The binding agent may generally be coated on a membrane or other microstructure, but can also be deposited in the channel. Thus, it should be understood that other types of microstructures can function as the media.

[0026] The channel portion of the media (400) may also be coated with various chemicals for performing tests such as assays on the collected sample.

[0027] Figure 2 is an example of a medium (400) having channels of a similar shape. However, here, a break line (406) (as indicated by the dotted line) defines individual compartments (408), along which the medium (400) may ultimately be split. For example, the initially collected blood may be capable of being separated, stabilized, and dried on the medium (400). After a period of time, such as that required to transport the medium (400) to a remote laboratory, the medium is split along the break line. In this example, the laboratory will have five (5) different compartments (408) of the medium (408) for processing. Of course, the medium (400) may have a different number of break lines than that shown in Figure 2, such that the number of compartments is less than 5 or more than 5.

[0028] The different compartments (408) of the medium (400) may serve different purposes. For example, a selected compartment (408) may be coated with different chemicals to perform different tests, such as an assay, on the cells collected in that compartment. Thus, a single medium (400) may be used to perform multiple tests and / or apply multiple reagents within a given compartment (408).

[0029] In other configurations, the different compartments (408) may have different filtering characteristics for processing different sized different cells.

[0030] Figure 3 is another example of a medium (400), where the channel (401) is a rectangle extending across the length of the medium (400).

[0031] Figure 4 is a medium (400) similar to the example of Figure 3, but having a break line (406) that defines a plurality of compartments (408).

[0032] Figure 5 is an exemplary medium (400) having a hydrophobic region (402) that defines two parallel channels (401-1), (401-2).

[0033] Figure 6 shows an implementation of the medium (400) that has only break lines defining different compartments (408) and no hydrophobic region patterning.

[0034] Figure 7 shows an example similar to Figure 6, but the break lines (406) run vertically across the medium (400) to define four (4) compartments (408).

[0035] Figure 8 is an exemplary embodiment where the break lines (406) run in both the vertical direction and the direction across the channels (401). Here, for example, nine (9) compartments of the medium (400) are outlined.

[0036] Figure 9 is yet another example of the medium (400), which has break lines (406) formed along the ends of the channels (401), that is, at the ends of the hydrophobic region pattern (402), near the ends, or equiangular to the ends.

[0037] In this and other embodiments, the medium (400) is also held in a housing (410) that is partially or fully formed by the hydrophobic region (402). Lat eral flow It may be a strip. The break lines (406) Lateral flow allow for separation of the strip from such a hydrophobic housing (410).

[0038] Figure 10 shows an example where the medium (400) includes a single channel (401) following a curved path.

[0039] Figure 11 is a similar implementation to Figure 10 having a single channel (401) following a curved path, but having three (3) break lines (406) that define four (4) compartments (408). Some of the compartments (408-1), (408-2), (408-3) include two (2) collection areas (409).

[0040] The embodiment of FIG. 12 is similar to that of FIG. 11, but has a break line (406) formed only on a specific part of the side surface of the channel (401). Therefore, when the medium (400) is split along the break line (406), compartments (408) of different sizes and shapes will result, different from the embodiment of FIG. 11.

[0041] FIG. 13 is another example similar to FIG. 12, where the break line follows a curved channel (401) along its entire length.

[0042] FIG. 14 shows a different configuration, where the medium (400) is coated with a substance (402) such as a hydrophobic substance. The hydrophobic substance (402) guides a blood sample into eight compartments formed in the channel (401). In this embodiment, the channel (401) may follow a curved path, but other paths are also possible. FIG. 14 also shows that the break line (406) does not necessarily run at the end of the channel.

[0043] FIG. 15 shows an example where a meandering channel (401) runs along the length of the medium (400), and has break lines (406) defining some compartments of the meandering channel. Compartments (408-1) and (408-2) may have different shapes and sizes. As in other embodiments, different compartments may be coated with various reagents.

[0044] Therefore, the hydrophobic region may define different types or shapes of the flow path of the channel (401). Paths with different shapes and lengths, such as the meandering paths shown or other types of serpentine paths, regulate and / or slow down the speed of fluid movement through or along the medium (400). Slowing down the speed of fluid sample movement may then allow the medium to more completely absorb the fluid through the resulting deceleration of capillary action.

[0045] FIG. 16 is similar to FIG. 15, but without a break line.

[0046] FIG. 17 shows another configuration of a break line having a meandering channel (401).

[0047] The embodiment of FIG. 18 is a “three-dimensional” implementation, where the channel occupies more than one layer. In this example, the channel (401) defined by the hydrophobic region (402) may start at the top layer (421) and may be straight as shown, or may be meandering, or may follow another path. The channel (401) on the top layer (421) defines a path to a location where fluid can pass through the intermediate layer (422). Here, the intermediate layer (422) is substantially a hydrophobic region (402) and has only selected small areas (408) or vias through which fluid can pass to the bottom layer (423). The bottom layer (423) may then define a path (410) (which may be straight as shown, or may be meandering, or may follow another path) bounded by the hydrophobic region (402). Each of these layers (421), (422), (423) may be made of different media materials or may have different hydrophobic or hydrophilic treatments to conduct fluid. Other three-dimensional configurations are possible, such as those having different patterns of channels (401) and (410), those having additional vias (408), and those having more than three layers. Embodiments with multiple layers may include break lines as described for other embodiments.

[0048] FIG. 18 may also be used to define a sample collection well (430), which leads a sample to a prefilter (such as one disposed within the via (408)) disposed on the bottom layer (423) that provides the strip. This configuration also allows the sample to Lateral flow be led to a prefilter (such as one disposed within the via (408)) disposed on the bottom layer (423) that provides the strip. This configuration also allows the sample to Lateral flowBefore being directed to the strip (410), it enables pre-treatment of the sample with a reagent contained in either channel (400) or (408). The hydrophobic region (402) maintains these layers and the reagent physically separated from the sample to reach in the intended order.

[0049] Figure 19 is an example of a blood collection device (100) that can use any of the media (400) as described herein. However, there are other types of devices that can use the media (400) and enjoy the advantages of the same principle. Some exemplary devices are described in co-pending U.S. Patent Application No. 16 / 164,988, filed October 19, 2018, as a "Fluid Sample Collection Device", the entire content of which is incorporated herein by reference.

[0050] The device (100) includes a two-piece housing (101) that supports and houses the fluid sample port (102). The housing (101) includes a first housing portion (101-A) and a second housing portion (101-B). In this figure, the housing is in the open position, and the two housing portions (101-A), (101-B) are spaced apart from each other, thus providing access to the sample port (102). A sample collection well (104) and one or more capillaries (105) located adjacent to the sample port (102) can be partially seen in the figure. Through the window (150) in the housing, the user can view the state of one or more portions of the fluid sample during the process of being collected and / or stored within the device (100).

[0051] The device (100) is initially in its open position as shown in FIG. 18, providing access to the well (104). A user, such as the patient himself or a medical professional, then uses a lancet to generate a blood sample, for example from the fingertip. A droplet of whole blood is then collected with that finger, located near, above, adjacent to, or even in contact with the well (104) or other parts of the sample port (102), minimizing blood leakage.

[0052] The blood is then finally drawn into the remainder of the device (100) in one or more different ways. As will be described in detail below for one embodiment, the blood flow first flows and / or is drawn from the well (104) via capillary action by one or more collection capillaries (105) adjacent to the sample port. The capillary may be visibly transparent so that the user can confirm that the blood is properly drawn into the device (100). The capillary (105) can optionally be pre-coated with a reagent such as heparin and / or EDTA for subsequent stabilization and storage of the sample. The capillary (105) can also have a known and predefined volume, in which case the inflowing sample is precisely measured. The collection capillary (105) then guides the measured sample to a medium (such as any of the media (400) described herein) inside the device housing (101).

[0053] A user, who can be the patient himself or a medical professional, then manually closes the device (100) by pressing the two housing parts (101-A), (101-B) together, thereby placing the sample on the medium (400).

[0054] FIG. 20 is a more detailed exploded assembly view of the components of the device (100).

[0055] The backbone structure (203) provides support for the housing parts (101-A), (101-B), enabling the housing parts to slide back and forth and thereby move the housing to the open or closed position.

[0056] The backbone (203) also supports other components of the device (100). For example, the backbone (203) supports a desiccant tablet (not shown) on the sample collection port (102), the plunger rack (202), or the ridge-like section (230), providing a place for further drying the collected sample. The backbone (203) also has tines at its ends, thereby providing a ratchet-type closure (240), which is activated when the two housing parts (101-A), (101-B) are pushed together.

[0057] The capillary (204) is inserted and held in place by a longitudinal hole in the inlay (252) part. The capillary may be formed of a precisely defined rigid tube, in which case the capillary also performs a measuring function. The capillary (204) extracts a defined quantity of blood by means of capillary action engagement with the blood in the sample collection port (102). The inlay (252) may fit into the hole (221) of the backbone (203). The capillary (204) may optionally be pre-coated with a reagent, heparin, EDTA, or other substance.

[0058] One or more capillaries (204) may also store a pre-determined quantity of a liquid reagent. Such a reagent may then be dispensed with or in parallel with the blood sample when the housing is moved from the open position to the closed position. However, other types of reagents may also be located in storage areas within the housing. The storage areas (not designated in the figure) 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 of which is arranged in the path of the blood sample collected by the device (100).

[0059] In one configuration, one or more plungers (202) engage tightly with the inner diameter of the capillary (204) to create a blocking portion that blocks any excess blood sample and also pushes the measured sample volume into subsequent downstream processing steps.

[0060] The base (206) may also fit into the backbone (203) to provide additional mechanical support to the medium (400) in the form of the blood collection membrane (209). The membrane-type medium may be supported / held in place by other components that assist in handling the membrane (209) when it is removed from the device (101) for laboratory processing.

[0061] In particular, this device (100) includes two media - the collection membrane (209) and the immunoassay strip (309). The membrane (209) and the strip (309) may be arranged in parallel. The collection membrane (209) receives and stores blood samples from several capillaries, and the immunoassay (or other test) strip (309) may receive and process blood samples emerging from other capillaries.

[0062] Figure 21 is an exploded view of a device (450) having a medium (400) formed of multiple layers of membranes. In this case, the medium (400) includes a first layer (412) that is a membrane having a hydrophobic compartment (402), and a second layer (416) that is a strip located below the first layer (412). The hydrophobic compartment (402) creates a channel (401) for guiding a fluid sample onto the sample pad (414) of the strip (416) located below. The channel (401) may be used to guide the sample into a housing (not shown) that holds these membranes in place. Additionally, one or more break lines (406) are provided to separate the membrane (412) having the channel from Lateral flow the strip (416) located below. Lateral flow the strip (416). Lateral flowPortions that are not in contact with the strip (416) can be cut off. This allows all sections of the membrane (412) that may contain undesired substances such as red blood cells to be removed from the housing without removing them, or simply fixed within the device, while Lateral flow the strip (416) can be removed. In some embodiments, Lateral flow the strip (416) itself may further include a plurality of strips or other collection media (400). Still further additional layers can be added as a means of providing reagents or directing fluid paths, or for holding other components in place, or for other purposes.

[0063] Figure 22 shows a section of a membrane-type medium (400) having a channel (401) that includes a plurality of branches (415) defined by a hydrophobic region (402). At the end of each branch (415), there is a circular area (418) bounded by a break line (406), which allows the circular area (418) of the membrane to be removed for analysis. These removable portions may be of various shapes other than circles and may be sized to ensure a desired volume of sample. Alternatively, these perforated areas (418) may function as removable reaction wells.

[0064] Figures 23A and 23B show another device (600) that defines a medium (400) that provides a strip using the principle of hydrophobicity. This device (600) consists of a movable or removable cap (601) and a main body (602). The sample collection port (610) provides a location for collecting a blood sample, the filling window (411) provides visual feedback as to whether a sufficient amount of sample has been introduced into the device (600), and the result window (612) Lateral flow allows for visual confirmation of the result area of the strip. Lateral flow

[0065] ​ In this embodiment, (620) is a liquid reagent reservoir, (621) is a fluid channel that connects the liquid reagent reservoir (621) to the sample collection port once the device is capped and / or the cap is slid inside to close the device, (622) is an empty area in the device where the sample collection port moves into when the device is closed, (623) is a rigid support under the strip that extends into the liquid reagent portion of the housing, Lateral flow (624) is provided by a medium (400) including one or more hydrophobic patterns and / or break lines as described in any of the above embodiments, Lateral f low a strip, (625) is, Lateral flow a sample absorption pad at the end of the strip, and (626) is a desiccant tablet.

[0066] Accordingly, it should be understood that various modifications and additions can be made to the embodiments described herein without departing from the true scope of the invention.

Claims

1. A medium having channels defined by at least one hydrophobic region, and at least one breaking line that intersects the channels and defines a predetermined area of the medium, wherein the partition of the medium is defined by the at least one breaking line, the partition of the medium surrounds the predetermined area of the medium, and the at least one breaking line is a perforation, and the medium is a membrane, a fluid sample collection device.

2. The fluid sample collection device according to claim 1, wherein at least one breaking line defines an area that provides a predetermined volume for the collection of a fluid sample.

3. Further comprising two or more breaking lines that define corresponding plural areas of the medium coated with a reagent, and at least one selection reagent coats a selection area different from another area coated with another reagent, the fluid sample collection device according to claim 1.

4. The fluid sample collection device according to claim 1, wherein the hydrophobic region further defines one or more fluid paths.

5. The fluid sample collection device according to claim 1, wherein the hydrophobic region regulates the speed of fluid movement.

6. The fluid sample collection device according to claim 5, wherein the hydrophobic region defines a meandering path to decelerate the movement of fluid through the device.

7. The fluid sample collection device according to claim 5, wherein the hydrophobic region decelerates the movement of the fluid and then partially saturates the medium to decelerate capillary action.

8. The fluid sample collection device according to claim 1, wherein the medium comprises a plurality of layers.

9. The fluid sample collection device according to claim 8, wherein the first layer is a first membrane that collects and guides a sample to a second layer through a channel defined by a hydrophobic region.

10. The fluid sample collection device according to claim 8, wherein one of the plurality of layers is a lateral flow strip.

11. The fluid sample collection device according to claim 8, wherein one of the plurality of layers contains a reagent.

12. The fluid sample collection device according to claim 8, wherein one of the plurality of layers redirects fluid flow through one or more of a hydrophobic material or a hydrophilic material.

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