BLOOD COMPONENTS COLLECTION AND SEPARATION MEDIA, BLOOD COMPONENTS COLLECTION AND SEPARATION DEVICE COMPRISING SAID MEDIA, AND BLOOD COMPONENTS SEPARATION AND EXTRACTION PROCESS IMPLEMENTING SAID MEDIA
20220338770 · 2022-10-27
Inventors
Cpc classification
B01L2200/0631
PERFORMING OPERATIONS; TRANSPORTING
B01D2239/086
PERFORMING OPERATIONS; TRANSPORTING
B01L2300/165
PERFORMING OPERATIONS; TRANSPORTING
B01L3/502753
PERFORMING OPERATIONS; TRANSPORTING
B01D39/2024
PERFORMING OPERATIONS; TRANSPORTING
B01L2300/0864
PERFORMING OPERATIONS; TRANSPORTING
B01D2239/0421
PERFORMING OPERATIONS; TRANSPORTING
A61B5/150755
HUMAN NECESSITIES
B01L2300/069
PERFORMING OPERATIONS; TRANSPORTING
B01L3/5023
PERFORMING OPERATIONS; TRANSPORTING
B01L2300/0816
PERFORMING OPERATIONS; TRANSPORTING
International classification
B01D39/16
PERFORMING OPERATIONS; TRANSPORTING
B01D39/20
PERFORMING OPERATIONS; TRANSPORTING
Abstract
The present invention relates to a blood components collection and separation media (1) comprising a substrate (3) having a maximal flow pore size enabling the retention of at least red cells on the surface of the substrate (3), the blood components collection and separation media (1) comprises boundary walls (7) forming a pattern (9) and being made of a hydrophobic resin, and the pattern (9) presenting: a collection zone (91); at least one storage zone (93) aimed at collecting at least one component of the whole blood sample (5); and at least one channel (95) connecting the collection zone (91) to the at least one storage zone (93), the channel (95) forming a bottleneck between the collection zone (91) and the storage zone (93). The present invention further relates to a blood components collection and separation device and a blood components separation and extraction process.
Claims
1. Blood components collection and separation media (1) comprising a substrate (3) capable of being wetted by a whole blood sample (5), the substrate (3) having a maximal flow pore size comprised between 8 μm and 35 μm, such maximal flow pore size enabling the retention of at least red cells (51) on the surface of the substrate (3), characterized in that the blood components collection and separation media (1) further comprises boundary walls (7) which form a pattern (9) into said substrate (3), said boundary walls (7) being made of a hydrophobic resin, and in that the pattern (9) presents: a collection zone (91) aimed at receiving the whole blood sample (5); at least one storage zone (93) aimed at collecting at least one component of the whole blood sample (5) after its separation through the substrate (3); and at least one channel (95) connecting the collection zone (91) to the at least one storage zone (93), said channel (95) forming a bottleneck between the collection zone (91) and the storage zone (93).
2. Blood components collection and separation media (1) according to claim 1, wherein the substrate (3) has a mean flow pore size comprised between 2.5 μm and 5 μm.
3. Blood components collection and separation media (1) according to claim 1, wherein the hydrophobic resin forming the boundary walls (7) is chosen among photo-curable resins, UV-curable resins, or thermosetting resins.
4. Blood components collection and separation media (1) according to claim 1, wherein the hydrophobic resin is chosen among fluorinated resins, modified fluorinated resins, latexes, glycol ether acrylates, acrylate esters, or a combination thereof.
5. Blood components collection and separation media (1) according to claim 1, wherein the collection zone (91) of the pattern (9) has a substantially parallelogram shape; and wherein the at least one storage zone (93) is disposed at an angle (97) of the substantially parallelogram shape of the collection zone (91); and wherein the pattern (9) presents as many storage zones (93) as the collection zone (91) has angles (97).
6. (canceled)
7. (canceled)
8. Blood components collection and separation media (1) according to claim 1, wherein the at least one storage zone (93) has a substantially circular shape.
9. Blood components collection and separation media (1) according to claim 1, wherein the at least one channel (95) has a length (1) comprised between 1 mm and 5 mm and a width (w) comprised between 1 mm and 3 mm.
10. Blood components collection and separation media (1) according to claim 1, wherein the substrate (3) is a fibrous web comprising: first fibers, said first fibers being chosen among glass micro-fibers or synthetic micro-fibers; second fibers, said second fibers being chosen among fibrillated fibers; and a hydrophilic binder.
11. Blood components collection and separation media (1) according to claim 10, wherein the hydrophilic binder is at least one of latex binders, polyvinyl alcohol binders, styrene-butadiene binders, vinyl-acetate binders, polysaccharide binders or protein binders.
12. (canceled)
13. (canceled)
14. (canceled)
15. (canceled)
16. (canceled)
17. Blood components collection and separation media (1) according to claim 10, wherein the fibrous web comprises between 5 and 7% by weight of the hydrophilic binder.
18. Blood components collection and separation media (1) according to claim 1, wherein the boundary walls (7) forming the pattern (9) exceed one surface of the substrate (3).
19. Blood components collection and separation media (1) according to claim 1, wherein the collection zone (91) further contains a salt capable of achieving at least partial crenation of red cells (51), the salt being chosen from the group of alkali metal and alkaline earth metal halogenides and sulfates, and hydrochlorides of organic bases.
20. Blood components collection and separation media (1) according to claim 1, wherein the boundary walls (7) extend at least through a whole depth (d) of the substrate (3).
21. Blood components collection and separation device (10), aimed at separating and collecting at least one component of a whole blood sample (5), wherein the blood components collection and separation device (10) comprises at least the blood components collection and separation media (1) according to claim 1 and a frame (11) surrounding the blood components collection and separation media (1).
22. Blood components separation and extraction process (100), wherein it implements a blood components collection and separation media (1) according to claim 1 and wherein it implements the following steps: deposition (S1) of a whole blood sample (5) in the collection zone (91); absorption (S3) of the whole blood sample (5) onto the substrate (3); retention (S5) of the red cells (51), the platelets (52) and the white cells (53) on the substrate (3) in the collection zone (91); diffusion (S7) of at least one component through the substrate (3) to the at least one storage zone (93); and extraction (S9) of at least one target component stored in the substrate (3) of the blood components collection and separation media (1).
23. Blood components separation and extraction process (100) according to claim 22, wherein the at least one target component is stored in the at least one storage zone (93) and wherein the extraction step (S9) of said at least one target component is performed by punching at least one part of said at least one storage zone (93) or by eluting said at least one target component from the at least one storage zone (93).
24. Blood components separation and extraction process (100) according to claim 22, wherein the at least one target component is stored in the collection zone (91) and wherein the extraction step (S9) of said at least one target component is performed by punching at least one part of said collection zone (91) or by eluting said at least one target component from the collection zone (91).
25. Blood components separation and extraction process (100) according to claim 22, wherein the whole blood sample (5) deposited in the collection zone (91) has a volume comprised between 50 μL and 500 μL.
26. Blood components separation and extraction process (100) according to claim 22, wherein the target component aimed at being extracted from the whole blood sample (5) is plasma (55).
27. Blood components separation and extraction process (100) according to claim 22, wherein the target component aimed at being extracted from the whole blood sample (5) is DNA, said DNA being stored in the white cells (53).
28. Blood components separation and extraction process (100) according to claim 22, wherein the target component aimed at being extracted from the whole blood sample (5) is lipids, said lipids being stored in the red cells (51).
Description
BRIEF DESCRIPTION OF THE DRAWINGS
[0098] Further advantages and characteristics will be better identified and understood with the following description, given as an illustrative and not a limitative way, and the enclosed drawings in which:
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DESCRIPTION OF EMBODIMENTS
[0110] On these figures and in the following description, the same elements have the same numeral references.
[0111] Moreover, the embodiment(s) in the following description are only to be considered as examples. Although the description refers to one or several embodiments, this does not mean inevitably that every reference concerns the same embodiment, or that characteristics apply only to a single embodiment. Simple characteristics of various embodiments can be also combined to provide new embodiments that are not explicitly described.
[0112] In the following, it is referred to a first and second element and/or parameter. Such indexation is only intended to differentiate two elements and/or parameters that are close but not identical. Such indexation can be interchanged without impacting the disposition or the implementation of those elements and/or parameters. Furthermore, this indexation is not intended to appreciate in time or in space the disposition of those first and second elements and/or parameters.
[0113] In the following, the following definitions are used.
[0114] A “whole blood sample” is any sample of blood from human or animal origin, stabilized or not, constituted by 55% plasma and 45% figured elements comprising erythrocytes (red blood cells), leucocytes (white blood cells) and platelets.
[0115] “Plasma” in whole blood generally comprises water and proteins. Typically, plasma contains about 92% water, 7% albumin, gamma globulin, anti-hemophilic factor and other clotting factors along with about 1% mineral salts, fats, hormones and vitamins, the percentage being calculated from the total weight of blood.
[0116] A “target component” is a component of a whole blood sample 5 aimed at being titrated after its extraction, such component being stored in the red cells 51, the platelets 52, the white cells 53, or the plasma 55.
[0117] “Pore size” (in μm) can be determined by the American Society of Testing and Materials (ASTM) Standard 316-03 (2011).
[0118] The maximum pore size, minimum pore size and mean flow pore size can measured using a technique known as capillary flow porometry. A sample of the nonwoven fibrous web sample is first wetted with a wetting fluid such that all the pores in the sample are filled. A nonreacting gas of increasing pressure is applied to one side of the wet sample to displace the wetting fluid from the pores. The gas pressure and gas flow rate downstream of the sample are measured and plotted for the wet sample. After the sample is dry, the test is repeated to plot a similar curve for the dry sample.
[0119] The “maximum pore size” is calculated from the bubble point, i.e., the gas pressure at which air flow through the wet sample is first detected. The term “mean flow pore size” is calculated from the gas pressure at which the flow through a wetted sample is 50% of the flow through the dry sample. The term “minimum pore size” is calculated from the pressure at which the wet flow rate curve merges with dry flow rate curve. The term “pore size range” is defined as the difference between the “maximum pore size” and the “minimum pore size” (i.e. Pore Size Range=Maximum Pore Size−Minimum Pore Size).
[0120] According to
[0121] The blood components collection and separation device 10 presents a length M and a width N. According to the particular embodiment of
[0122] The frame 11 can be made of cardboard (also called “paperboard”). Advantageously, cardboard is a rigid material generally low cost and biodegradable. Such frame 11, made of cardboard, also enables a reduction of the production costs of this blood components collection and separation device 10 as well as reducing the amount of non-biodegradable waste. Furthermore, even if this blood components collection and collection device 10 is aimed at being used by a human or by an automaton, this device has to present a minimal rigidity in order at least to enable this device be easily taken and processed by the human or the automaton. The use of cardboard for the frame 11 enable to easily adapt the length M and the width N of the blood components collection and separation device 10 as such material is easy to cut for example. This frame 11 can be further constituted by other rigid materials such as wood, plastic, metal.
[0123] According to the particular embodiment of
[0124] Optionally and as represented on
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[0126] In the embodiments depicted, the substrate 3 is aimed at, and preferably capable of being wetted (for example fully wetted), by the whole blood sample 5. The substrate 3 has a maximal flow pore size comprised between 8 μm and 35 μm, such maximal flow pore size enabling the retention of at least red cells 51 in the substrate 3. More particularly, the substrate 3 presents a maximal flow pore size configured for the retention of the red blood cells 51 and the white blood cells 53 at its surface. According to a particular embodiment, the maximal flow pore size of the substrate 3 can be preferably comprised between 9.5 μm and 10.5 μm. In addition or as a further variant, the substrate 3 further can have a minimal flow pore size comprised between 0.5 μm and 2 μm, and preferably comprised between 0.9 μm and 1.3 μm. Then, still in addition or as an alternative, the substrate 3 can have a mean flow pore size comprised between 2.5 μm and 5 μm, and preferably comprised between 3 μm and 3.5 μm. Such characteristics for the substrate 3, taken alone or in combination, enable the substrate 3 to separate plasma 55 (represented on
[0127] According to the particular embodiment of
[0128] The first fibers may present one or more of the following characteristics: a diameter of less than 5 μm, and preferably comprised between 0.4 μm and 1 μm, a specific surface area greater than 1.5 m.sup.2/g, a length/diameter ratio greater than 100 and more preferably greater than 500. Such characteristics for the first fibers of the substrate 3 enable to retain the red blood cells 51 through the substrate 3 and also slow down their diffusion speed through the substrate 3 compared to the plasma 55 and enable the separation of the components forming the whole blood sample 5 through this substrate 3. Such characteristics for the first fibers will have improved affinity with red blood cells 51.
[0129] The second fibers can be cellulosic-based fibers, and in particular cotton linters, lyocell, or viscose fibers. According to the particular embodiment of
[0130] Optionally, the fibrous web can comprise at least one additive for improving characteristics of the substrate 3. For example, this additive can be a stabilizing agent for biomarkers extracted from the plasma 55, for example an animal protein as bovine serum albumin (BSA) or gelatin derivatives. According to another aspect, this stabilizing agent can be sucrose to retain humidity and also preserve the biomarkers.
[0131] In the embodiment shown
[0132] The boundary walls 7 are made of a hydrophobic resin. The use of a hydrophobic resin extending at least through the whole depth d of the substrate 3 enables to maintain the whole blood sample 5 into the pattern 9 and also the separation of its several components in this pattern 9. Furthermore, the use of a hydrophobic resin for forming the boundary walls 7 enables the plasma 55 to be easily guided without any risk for this constituent to diffuse outside the pattern 9. More particularly, the hydrophobic resin forming the boundary walls 7 can be chosen among photo-curable resins, more preferably UV-curable resins, or thermosetting resins. According to another embodiment, the hydrophobic resin can be chosen among fluorinated resins, modified fluorinated resins, latexes, glycol ether acrylates, acrylate esters, or a combination of thereof. More particularly, the hydrophobic resin can be chosen among a polymethyl methacrylate resin (PMMA) or a polydimethylsiloxan resin (PDMS). Such hydrophobic resins can be applied onto the substrate 3 without any contact with the fibrous web, such as by a non-contact dispensing system for example. According to another embodiment, the hydrophobic resin can be applied onto the substrate 3 with contact with the fibrous web, such as by screen printing for example.
[0133] Still referring to
[0134] The collection zone 91 can be dimensioned to receive a volume of whole blood sample 5 that can be comprised between 50 and 500 μL. Moreover, the collection zone 91 can be aimed at being punched in order to allow the collection of a component of the whole blood sample 5 (represented on
[0135] According to a particular embodiment, the collection zone 91 can further contain a salt capable of achieving at least partial crenation of red cells 51. The crenation of the red blood cells 51 enables to improve the separation of speed of the components of the whole blood sample 5. This salt can be chosen from the group of alkali metal and alkaline earth metal halogenides and sulfates, and hydrochlorides of organic bases, and more particularly among calcium chloride, potassium sulfate, or guanine hydrochloride. The salt may be present at a concentration in the substrate 3 comprised between 1 and 25% of the total weight of the substrate 3, and more particularly between 10 and 20% of the total weight of the substrate 3.
[0136] The storage zone 93 can be aimed at being punched and/or eluted in the case where the component of the whole blood sample 5, such as plasma 55 for example, aimed at being extracted has diffused to the storage zone 93. Furthermore, according to the particular embodiment illustrated by
[0137] According to the specific embodiment illustrated by
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[0139] More particularly, according to the first particular embodiment illustrated by
[0140] Furthermore, according to the second particular embodiment, illustrated by
[0141] Still referring to the particular embodiment of
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[0143] Now referring to
[0144] The blood components separation and extraction process 100 implements a deposition step S1 of a whole blood sample 5 in the collection zone 91. This deposition step S1 is better illustrated on
[0145] Then, the blood components separation and extraction process 100 implements an absorption step S3 of the whole blood sample 5 onto the substrate 3. The separation of the blood components of the whole blood sample 5 starts during this absorption step S3. At the same time, the blood components separation and extraction process 100 implements a retention step S5 of the red cells 51, the platelets 52, and the white cells 53 on the substrate 3 in the collection zone 91. Moreover, still in parallel of those absorption S3 and retention S5 steps, the blood components separation and extraction process 100 implements diffusion S7 of at least one component through the substrate 3 to the at least one storage zone 93. Those different steps are illustrated by
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[0147] Furthermore, this blood components separation and extraction process 100 can be aimed at being implemented by an automaton. In such a case, the deposition step S1 is directly implemented by the automaton and the extraction step S9 of performed directly by the automaton after a given time, said given time depending for example on the volume of the whole blood sample 5, or the porosity of the substrate 3 forming the blood components collection and separation media 1. In such a case, the blood components collection and separation device 10 presents the at least two indicators 15 (represented on
[0148] The several embodiments described here-above are examples given in an illustrative manner and not a limitative one. Indeed, the man skilled in the art can envision other ranges for the length M and the width N of the blood components collection and separation device 10; or adapt the flow pore sizes of the substrate 3, the depth d of the substrate 3 without departing from the teachings of the present specification. Furthermore, the man skilled in the art can adapt the kinds and properties of additives aimed at being added to the fibrous web in order to change the properties of the substrate 3. Then, the dimensions of the collection zone 91, of the storage zone 93 and of the channels 95 can be changed to be adapted to the volume of the whole blood sample 5, and also envision greater volumes of whole blood samples 5 without departing from the teachings of the here-above disclosed embodiments. Moreover, the number of indicators 15 as well as their shape can be changed without departing from the present teachings. Then, other elements than the triangle 12 or the notched angle 13 can be envisioned to determine the position of the blood components collection and separation device 10.
[0149] Thus, it is possible to simplify the deposition and the extraction of blood components from a whole blood sample 5 due to the blood components collection and separation media 1 as disclosed here-above. Indeed, the pattern 9, comprising at least one channel 95, formed by the boundary walls 7 enable a direction of the plasma 55 to the at least one storage zone 93. Moreover, this pattern 9 allows a simplification of the deposition of the whole blood sample 5, because it is only necessary to dispose the whole blood sample 5 anywhere in the collection zone 91, the several components being then separated through the substrate 3 and the diffusion of those components in the several zones of the pattern 9 being allowed by the at least one channel 95. Furthermore, such a blood components collection and separation media 1 enables an automation of the blood components separation and extraction process 100.