This patent relates to precise collection of body fluids, such as a blood sample.
Blood used for diagnostic testing is most often extracted from a patient with a hypodermic needle and collected in a test tube. The collected blood is then packaged for shipment to a remote lab where various diagnostic tests are performed. However, many diagnostic tests require significantly less volume than the actual collected sample. Separation of cellular components from the sample is also needed for some tests.
Many tests only require small blood samples, where a finger stick rather than a hypodermic needle can produce enough blood. Convenient and widely accessible methods of collecting and preserving small, accurately measured amounts of blood are still needed, however.
A medium such as a membrane is used to collect a body fluid sample such as a blood sample. The membrane has hydrophobic patterns to define precisely dimensioned channels for fluid flow. break lines in the membrane defined predetermined areas (or volumes) of the membrane. After collection and transport, the membrane may be broken apart along the break lines to obtain a precisely measured blood sample.
More particularly, in one embodiment a device may include a medium, such as a membrane or microstructured environment, having a channel defined by at least one patterned hydrophobic region. At least one break line intersects the channel to define a predetermined area or collection volume of the medium.
The break lines can be used to define different areas of the medium that can be easily detached for further processing.
In some embodiments, two or more the break lines may define corresponding multiple areas of the medium. The different areas may be coated with different reagents, or may be of differing sizes or shapes.
The hydrophobic region or corresponding regions may define fluid pathways. The pathways can direct fluid samples to different areas, or regulate the fluid's speed of movement, or to encourage further saturation of the medium.
The medium may include multiple layers, some of which may be membranes, and others of which may be lateral flow strips that contain reagents, conjugates, or other materials.
The layers may contain hydrophobic or hydrophilic materials to further direct the fluid.
This patent application describes a membrane, or other medium such as a microstructured environment, medium that collects and stores precisely defined amounts of a blood or other fluid sample. In general, the medium has one or more channels defined by a wax or other hydrophobic region. In some embodiments, the channels can be defined by creating immiscible hydrophobic regions. Hydrophobic regions in the media can be arranged such that liquids are prevented from entering a region either from hydrophobic forces, via physical occlusion or similar physical barrier.
The one or more channels defined by wax or some other hydrophobic region direct the fluid while it is in the process of being collected along a defined path. These hydrophobic regions can not only be used to define paths but also keep reagents or layers of the medium separate. In addition, the hydrophobic region(s) can be used to define a reaction well where a sample is mixed with a reagent.
The hydrophobic regions may define different types or shapes of fluid pathways. Differently shaped and lengthened paths, such as serpentine or other tortuous paths, may be utilized to regulate and/or slow the speed of fluid movement through or along the medium. Slowing the speed of fluid sample movement may, in turn, allow the medium to more fully absorb the fluid, such as via a resulting slowed capillary action.
The medium may, in some embodiments, be enclosed within several different types of device housings that form a sample collection device.
In some embodiments, sections of the medium may be defined by break lines such as perforations. The sections may outline predetermined area(s) of the medium and/or further define one or more flow path(s). The break lines allow the medium to be subsequently split into sections that have collected predefined volume(s) of the fluid.
The break lines may take the form of different shapes. In one embodiment, break lines in the shape of one or more circles may allow precise volume of a dried body fluid sample, such as a blood sample, to be collected and easily removed from the medium. Currently circular holes are punched out of dried blood spot cards and predefining the circle could aid in automation. break lines can also allow for the easy detachment of a test region from the rest of the device.
In some embodiments break lines may allow for detachment of an assay region as well as a sample region which may then be used for subsequent analysis. In some embodiments break lines may define or control flow rate by narrowing channels. In some embodiments, break lines separate areas of membrane may be treated with different reagents.
The medium may also include a device that provides a microstructured environment. For an environment composed of a number of elements, such as fibers, pores or pillars, arranged in such a way that create a field that slows the flow of specific elements of a fluid such as red cells, white cells or other cellular materials.
Although only one side of the medium 400 is shown, it should be understood that the hydrophobic region may typically be coated on both face of the medium 400 or fully permeate the membrane 400. In some embodiments a section of medium 400 such as channel 401 may also be partially coated with a hydrophobic region to slow the flow of fluid through this section.
The medium 400 may be planar sheet of a sample medium such as a plasma separation membrane or filter of various types. For example, a mixed-cellulose ester membrane such as the Pall Vivid Plasma Separation available from Pall™ Corporation may be used. The membrane may also be an LF1 glass fiber membrane (sold by General Electric™ Company) or some other medium designed to receive serum or whole blood, which it then separates into a blood portion and a plasma portion.
A membrane-type medium 400 such as LF1 paper has a fibrous structure that causes differential migration of the sample, with a slower rate for red cells, resulting in a gradual separation of plasma sample as it migrates down the channel defined. LF1 paper, which separates plasma from red blood cells through a fiber matrix, is preferred in some embodiments, because it causes a slower migration rate for the blood cells. However other types of separation membranes for blood either liquid or dried may be used for the medium 400. The medium 400 can optionally be previously impregnated with heparin, EDTA, sugars, or other stabilization agents.
Plasma separation may also be achieved through mediums that are non-membrane microstructures that exclude red cells by size. For example, plasma separation can be achieved or enhanced by selectively binding red cells with an agent. Binding agents may typically be coated on a membrane or other micro structures but could also be deposited in a channel. Therefore, it should be understood that other types of microstructures can serve as the medium.
The channel portion of the medium 400 may also be coated with various chemicals to perform a test, such as an assay, on the collected sample.
The different sections 408 of the medium 400 may serve different purposes. For example, selected sections 408 may be coated with different chemicals to perform different tests, such as an assay, on the cells collected in that section. Thus, a single medium 400 may be used to perform multiple tests and/or apply multiple reagents in the predetermined sections 408.
In other arrangements, the different sections 408 may have different filtering properties, to process different cells of different sizes.
In this and the other embodiments, the medium 400 may also be a lateral flow strip held in a housing 410 which is partially or fully formed from the hydrophobic region 402. break lines 406 allow the separation of the lateral flow strip from such a hydrophobic housing 410.
The embodiment of
The hydrophobic region regions may therefore define different types or shapes of fluid pathways for the channel(s) 401. Differently shaped and lengthened paths, such as the illustrated serpentine path, or other types of tortuous paths, may regulate and/or slow the speed of fluid movement through or along the medium 400. Slowing the speed of fluid sample movement may, in turn, allow the medium to more fully absorb the fluid, such as via a resulting slowed capillary action.
The embodiment of
The device 100 includes a two-piece housing 101 that supports and encloses a fluid sample port 102. The housing 101 includes a first housing piece 101-A and second housing piece 101-B. In this view, the housing is in the open position with the two housing pieces 101-A, 101-B spaced apart from one another, to provide access to the sample port 102. A sample collection well 104 and one or more capillaries 105 located adjacent the sample port 102 are partially visible in this figure. A window 150 in the housing permits a user to confirm the status of one or more portions of a fluid sample in the process of being collected and/or stored within the device 100.
The device 100 is initially presented in its open position, as per
Blood is then eventually drawn into the rest of the device 100 in one or more different ways. As will be explained in more detail below for one embodiment, blood flows and/or is first drawn from the well 104 by one or more collection capillaries 105 adjacent to the sample port via capillary action. The capillaries may be visibly transparent so that the user can confirm that blood is being properly drawn into the device 100. The capillaries 105 can optionally be pre-coated with reagents such as heparin and/or EDTA for subsequent stabilization and preservation of the sample. The capillaries 105 can also have a known and predetermined volume, in which case the incoming sample is precisely metered. The collection capillaries 105 then direct the metered sample to a medium (such as any of the medium 400 described herein) inside the device housing 101.
The user, who can be the patient himself/herself or a healthcare professional, then manually closes the device 100 by pushing the two housing pieces 101-A, 101-B together, causing the sample to be deposited onto the medium 400.
A backbone structure 203 provides a support for the housing pieces 101-A, 101-B, allowing them to slide back and forth, and thus to move the housing into the open or closed position.
The backbone 203 also supports other components of the device 100. For example, the backbone 203 provides a location for the sample collection port 102, a plunger rack 202, or a ribbed section 230 to support a desiccant tablet (not shown) to further dry the collected sample. The backbone 203 may also have tines at an end that provide a ratcheting closure 240, which is activated when the two housing pieces 101-A, 101-B are pushed together.
Capillaries 204 are inserted into and held in place by longitudinal holes in an inlay 252 piece. The capillaries and may be formed as a rigid tube of precisely defined volume, in which case they also serve a metering function. The capillaries 204 extract a defined quantity of blood by engagement with the blood in the sample collection port 102 through capillary action. The inlay 252 may fit into a hole 221 in backbone 203. The capillaries 204 can optionally be pre-coated with reagents, heparin, EDTA, or other substances.
One or more capillaries 204 may also store a predetermined amount of a liquid reagent. Such a reagent may then be dispensed together or in parallel with the blood sample when the housing is moved from the open to the closed position. However, reagents of other types may also be located in a storage region within the housing. The storage region (not designated in the Figures), may hold a first type of reagent such as a solid surface or substrate, and a second type being a liquid storage chamber, each of which are placed in the path of the blood sample collected by the device 100.
In one arrangement, the one or more plungers 202 firmly engage with the inner diameter of the capillaries 204, creating a shutoff that blocks off any excess blood sample while also pushing the metered sample volume to the subsequent downstream processing steps.
A base 206 may also fit into the backbone 203 to provide additional mechanical support for the medium 400 in the form of a blood collection membrane 209. The membrane-type medium may be supported and/or held in place by other components that assist with handling the membrane 209 when it is removed from the device 101 for processing by a laboratory.
This particular device 100 has two media—including 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 receives and stores a blood sample exiting from some capillaries, and the immunoassay (or other test) strip 309 may receive and process a blood sample exiting from other capillaries.
In this embodiment:
620 is a liquid reagent reservoir;
621 is a fluid channel that connects the liquid reagent reservoir 621 with the sample collection port once the cap is placed on and/or slid inward to close the device;
622 is an empty region in the device that the sample collection port moves into when the device is closed;
623 is a rigid support underneath the lateral flow strip that extends into the liquid reagent portion of the housing;
624 is a lateral flow strip provided by a medium 400 contains one or more hydrophobic patterns and/or break lines as described in any of the embodiments above;
625 is a sample absorbent pad at the end of the lateral flow strip; and
626 is a desiccant tab.
Therefore, it should be understood that in light of the above, various modifications and additions may be made to the embodiments described herein without departing from the true scope of the inventions made.
This application claims priority to a co-pending U.S. Provisional Application Ser. No. 62/896,715 filed Sep. 6, 2019, and to a co-pending U.S. Provisional Application Ser. No. 63/060,279 filed Aug. 3, 2020, each of which is hereby incorporated by reference in its entirety.
Number | Date | Country | |
---|---|---|---|
62896715 | Sep 2019 | US | |
63060279 | Aug 2020 | US |