WO2008097573A1 - A device and method for sclerythrocytapheresis - Google Patents

Abstract

A device and a method for sclerythropheresis that include a screen for the selection of deformable erythrocytes and the blockage of hard erythrocytes in whole blood.

Description

A DEVICE AND A METHOD FOR SCLERYTHROCYTAPHERESIS

RELATED APPLICATION

[0001] This application is based on and claims priority to United States Provisional

Application Serial No. 60/888,409, filed on February 6, 2007, entitled Sclerythropheresis Using Artificial Spleen, to which a claim of priority is hereby made and the disclosure of which is incorporated by reference.

FIELD OF THE INVENTION

[0002] The present invention relates generally to a device and a method of selective removal of hardened, old erythrocytes from whole blood to increase the relative content of young erythrocytes in whole blood.

BACKGROUND OF THE INVENTION

[0003] The purpose of blood circulation is to deliver oxygen and nutrition to peripheral tissues. The carriers of the oxygen in blood are hemoglobin molecules in erythrocytes. Because the erythrocytes are the carriers of oxygen, it may be expected that having more erythrocytes in a given volume of blood is better. However, because whole blood viscosity critically depends on the content of erythrocytes increasing the content of erythrocytes results in the increase of whole blood viscosity. Note that the volume fraction, i.e. the relative content, of the erythrocytes in whole blood is often called hematocrit.

[0004] The life of erythrocytes is approximately 120 days. Young erythrocytes are very flexible and deformable. On the other hand, the old erythrocytes become less deformable or hardened. Old and less deformable erythrocytes cause a number of adverse effects on blood circulation. For example, the old, less deformable erythrocytes increase whole blood viscosity much more than the young, deformable erythrocytes. As the whole blood viscosity increases, the blood flow rate decreases, which can result in the retardation of oxygen delivery to the tissues. [0005] For maximum oxygen delivery the volume fraction of the erythrocytes in whole blood should be increased while decreasing whole blood viscosity. Hence, there is a trade-off between increased erythrocytes and decreased blood viscosity.

[0006] In order to find maximum oxygen delivery, the ratio of the hematocrit to blood viscosity corresponding to high shear viscosity (i.e., shear rate greater than 300 s^"1) can be used, which can be called oxygen delivery index (ODI). Most healthy male adults and female adults after menopause have values of hematocrit in a range of 45-50%. However, the range of the hematocrit for the optimum oxygen delivery is approximately 40% or below. Hence, to improve oxygen delivery a hematocrit of, for example, 50% should be reduced to or below about 40% by, for example, reducing the volume fraction of the erythrocytes, which can be accomplished by removing a fraction of the erythrocytes from the whole blood.

[0007] The procedure for removing blood constituents such as plasma, erythrocytes, leukocytes, or platelets is generally called apheresis. For example, plasma hyperviscosity is treated by exchanging plasma containing excessive paraproteins, fibrinogen, IgM, IgG, lipoproteins and others with a fluid of desired rheological properties such as plasma- volume expanders, including the Dextran solutions. In the case of polycythemia vera, where the hematocrit can increase beyond 60%, the erythrocytes can be removed to reduce the hematocrit, a procedure which is called erythrocytapheresis. Note that erythrocytapheresis minimizes the risk of hypo- or hypervolemia, where plasma volume is reduced via venesection or expanded, respectively. Moreover, excessive amounts of leukocytes can be removed to improve microcirculation, for example, through leukopheresis.

[0008] TThhee ffoolllloowwiinr g references disclose methods for the removal of erythrocytes:

[0009] US 6902539 6/2005 Bainbridge (Gambro)

[0010] US4350156 9/1982 Malchesky (Japan Foundation of

Artificial Organs)

[0011] US 6080322 6/2000 Deniega (Baxter)

[0012] US 6527957 3/2003 Deniega (Baxter)

[0013] US 5919369 6/1999 Ash (Hemocleanse) [0014] US 6099730 8/2000 Ameer (MIT)

[0015] US 5911698 6/1999 Cham (Aruba International)

[0016] US 4648974 3/1987 Rosskopf (Intermedicat BamH)

SUMMARY OF THE INVENTION

[0017] Since the old and less deformable erythrocytes significantly increase blood viscosity much more than the young and deformable erythrocytes, it is desirable in the process of the erythrocytapheresis to remove only the old and less-deformable erythrocytes from the whole blood, leaving the young and deformable erythrocytapheresis in the blood. In the present application the selective removal of the old and less deformable erythrocytes is referred to as sclerythrocytapheresis.

[0018] An objective of the present invention is to selectively remove the old and less deformable erythrocytes from the whole blood while leaving the young and deformable erythrocytes in the blood.

[0019] hi a device and a method according to the present invention, a screen having openings that allow for the passage of deformable erythrocytes is used to allow for the selection of deformable erythrocytes and the blockage of hard erythrocytes.

[0020] Other features and advantages of the present invention will become apparent from the following description of the invention which refers to the accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Fig. 1 schematically illustrates a device according to a first embodiment of the present invention.

[0022] Fig. 2 illustrates a cross-sectional view of a device according to the first embodiment along line 2-2 in Fig. 1 viewed in the direction of the arrows.

[0023] Fig. 3 illustrates a cross-sectional view of a device according to the first embodiment along line 3-3 in Fig. 1 viewed in the direction of the arrows. [0024] Fig. 4 illustrates a tubular screen suitable for use in an embodiment of a device or method according to the present invention.

[0025] Fig. 5 illustrates a portion (portion 5 from Fig. 4) of a screen according to a preferred embodiment of the present invention.

[0026] Fig. 6 illustrates how a screen according to the present invention separates hard and deformable erythrocytes.

[0027] Fig. 7 illustrates how deformable erythrocytes pass through a screen according to the present invention.

[0028] Fig. 8 illustrates how hard erythrocytes are blocked by a screen according to the present invention.

[0029] Fig. 9 illustrates a cross-sectional view of a device according to the second embodiment of the present invention as it would be viewed in the direction of the arrows along line 2-2 in Fig. 1.

[0030] Fig. 10 illustrates a cross-sectional view of a device according to the second embodiment of the present invention as it would be viewed in the direction of the arrows along line 3-3 in Fig. 1.

[0031] Fig. 11 illustrates a perspective view of a device according to the third embodiment.

[0032] Fig. 12 illustrates a cross-sectional view of the device of Fig. 11 along line 12-12 viewed in the direction of the arrows.

[0033] Fig. 13 illustrates a cross-sectional view of a device according to the fourth embodiment as it would be viewed in the direction of the arrows along line 12-12.

[0034] Fig. 14 illustrates an arrangement that includes a blood pump prior to the inlet of the chamber of a device according to the present invention.

[0035] Fig. 15 illustrates an arrangement including a blood pump and a vacuum pump both of which assist the flow of blood through the chamber of a device according to the present invention. DETAILED DESCRIPTION OF THE EMBODIMENTS

[0036] Referring to Figs. 1-3, an apheresis device according to an embodiment of the present invention includes a chamber 10, and a screen 12 disposed inside chamber 10 separating the space inside chamber 10 into first space 14 and second space 16. First space 14 is generally the space in the interior of screen 12, i.e. space surrounded by screen 12, and second space 16 is the space between the exterior surface of screen 12 and opposing interior surfaces of chamber 10. [0037] Chamber 10 includes a first opening 18 which is in direct communication with first space 14 and serves as an inlet port into chamber 10 and more specifically into first space 14. Chamber 10 may preferably include a second opening 20 which is in direct communication with second space 16 to serve as an outlet port. In use, first space 18 allows for the deposition of whole blood containing flexible and hard erytherocytes inside first space 14 (i.e. interior of screen 12), and second opening 20 serves as a port for receiving whole blood that has passed through screen 12 and reached second space 16.

[0038] Young erythrocytes are soft, flexible and deformable, whereas old erythrocytes are hard, not flexible and less deformable. The old erythrocytes become hard due to shrinkage with age rendering the cell membrane thereof stiff. Hence, the old cells cannot easily deform due to stiff membrane structure thereof.

[0039] Note that screen 12 can be preferably in the form of a bag positioned vertically

(i.e. along the central axis of chamber 10) inside chamber 10. As blood enters the bag and the old and hardened erythrocytes are collected to fill the bag, the bag may be stretched out vertically due to the weight of the collected erythrocytes.

[0040] According to an aspect of the present invention, screen 12 allows for selective passage of flexible erythrocytes and selective hindrance of passage of hard erythrocytes. Thus, whole blood that has passed through screen 12 from first space 14 into second space 16 includes a lower content of hard erythrocytes. [0041] According to a specific aspect of the present invention, screen 12 includes a plurality of openings large enough to allow passage of flexible erythrocytes, while the openings are small enough to hinder passage of hard erythrocytes.

[0042] Referring now to Figs. 4-8, screen 12 may be a fish-net type of arrangement which has been formed into, for example, a generally cylindrically-shaped body or tubular (see Fig. 4 specifically).

[0043] In order to prepare a sufficient volume for the collected hardened erythrocytes, the volume of the tubular structure should be larger than a certain value. For example, given that the total volume of whole blood in a body of approximately 5 liters and the value of hematocrit of 50%, the volume of the erythrocytes can be about 2.5 liters. Assuming that the goal of the hemopheresis is to reduce a maximum reduction of hematocrit of 20%, the volume of the tubular structure can be 500 ml. Furthermore, assuming that the length of the tubular structure is 20 cm, the diameter of the tubular structure should be 5.6 cm.

[0044] As illustrated specifically by Fig. 5, the fish-net that constitutes an embodiment of a screen 12 according to the present invention is made of a weave of, for example, 1 micron wide fibers 22, which form together a lattice having, for example, 3 micron X 3 micron wide openings 24. Note that a screen according to the present invention need not have the dimensions of 3 micron X 3 micron. Rather, it may have any dimension as long as the openings therein allow passage of soft erythrocytes.

[0045] Referring now to Fig. 6, a screen 12 according to the present invention allows for passage of deformable erythrocytes 26 from first space 14 into second space 16. However, screen 12 blocks the passage of hard erythrocytes 28 from first space 14 into second space 16, because opening 25 are too small to allow passage of hard erythrocytes 28 which are typically about 8 microns as specifically illustrated by Fig. 8. Deformable erythrocytes 26 can be deformed into an elliptic shape or be folded into a cane or umbrella shape to pass through openings in screen 12 despite being about 8 microns due to the flexibility thereof just as they would pass through capillaries in a human body that are about 2-5 microns wide, as illustrated specifically by Fig. 7. [0046] Thus, according to an aspect of the present invention, each dimension of an opening in a screen according to the present invention can be in the range of approximately 2-5 microns in that such a range is known to allow passage of flexible erythrocytes while hindering passage of hard erythrocytes.

[0047] Referring back to Figs. 1-3, chamber 10 in a first embodiment of the present invention is cylindrical. Also, screen 12 may be a generally cylindrical body. Interior space of screen 12 defines first space 14, while second space 16 is defined by the exterior surface of the cylindrical screen 12 and an interior wall 30 of chamber 10. Note that the top edge of screen 12 may be secured to the interior wall 30 of chamber 10 using an annular ring-shaped top plate 32 (a portion of which is removed from view in Fig. 2 to illustrate second space 16). The outer edge of plate 32 may reside against interior wall 30 of chamber 10 while the interior edge thereof can define an opening over first space 14 as illustrated by Fig. 2.

[0048] Referring to Fig. 3, a solid, preferably circular disk 34 may be used in the first embodiment to close the end of a cylindrical screen 12. Thus, in the first embodiment, screen 12 may include an open end for receiving whole blood, and a closed end.

[0049] Referring now to Figs. 9 and 10, in which like numerals identify like features, in a second embodiment of the present invention, plate 32 may be a circular body that includes a plurality of preferably circular openings therein. The mouth (i.e. open end) of a screen 12 is secured to the edge of each opening in plate 32. Thus, in the second embodiment, a plurality of screens 12 are provided inside a single chamber 10. Similar to the first embodiment, a respective plate 34 closes an end of each screen 12. Preferably, each screen 12 in a device according to the second embodiment is also cylindrically shaped.

[0050] Referring now to Figs. 11 and 12, in which like numerals identify like features, a device according to the third embodiment of the present invention includes a generally cubically- shaped chamber 10, and a planar screen 12 which extends from one interior wall 36 of chamber 10 to another, opposing wall 38 thereof to define a first space 14 and a second space 16 therein. Note that preferably screen 12 slopes (i.e. is tilted) negatively (in a descending manner) from wall 36 to wall 38 in order to create a ramp-like surface on which whole blood may travel downwardly.

[0051] Referring now to Fig. 13, in which like numerals identify like features, in a device according to the fourth embodiment of the present invention, a second screen 12' is provided to define a third space 40 inside chamber 10. In the fourth embodiment, third space 40 is in direct communication with second opening 20 which preferably serves as an outlet port for the device. Note that preferably second screen 12' extends from interior wall 36 to interior wall 38 of chamber 10 in an ascending manner (i.e. second screen slopes positively). Thus, preferably screen 12 and second screen 12' slope oppositely. In a similar manner, further embodiments can include a rectangular structure with 3, 4, or 5 tilted fish-net type screens without deviating from the present invention.

[0052] An advantage of the third and fourth embodiments is that old and hardened erythrocytes will be collected from the end of screen closest to first opening 18, thus the continuous entry of blood flow is not hampered. Thus, young and deformable erythrocytes pass through flat screen 12 and fall down by the inlet pressure and gravity toward second opening 20. [0053] Preferably, the first space 14 can be approximately 500 ml such that one can reduce the value of hematocrit by a maximum 20%.

[0054] Advantageously, in the fourth embodiment, two screens increase the efficiency of the removal of hard erythrocytes. Note that second screen 12' is also tilted (i.e. sloped) in order to promote the early collection of hard erythrocytes in order to not hamper blood flow. [0055] In an arrangement according to a preferred embodiment of the present invention, blood enters chamber 10 through first opening 18 with an increased pressure via a blood pump 19 as shown in Fig. 14. Blood leaves chamber 10 through second opening 20 with a reduced pressure. The pressure in the blood decreases as blood moves from first opening 18 to second opening 20 due to the friction between the blood and screen 12. To further accelerate the separation process, one can use a vacuum pump 21 after second opening 20 with a second chamber 23 as shown in Fig.15. [0056] In a method according to the present invention, whole blood containing deformable as well as hard erythrocytes are deposited inside first space 14. The whole blood so deposited is then screened with the application of an external pressure as shown in Figs. 14 and

15. That is, hard erythrocytes are trapped inside first space 14 while whole blood containing hard erythrocytes pass through screen 12 into second space 16. Alternatively, the whole blood is screened preferably without the application of an external pressure under gravity.

[0057] As a result, old and hardened erythrocytes are collected and left inside screen 12

(which can be in the form of a bag or the like), whereas plasma and the young and deformable erythrocytes pass through screen 12, leaving the bag which constitutes screen 12.

[0058] Thereafter, blood can be removed from second space 16 preferably through second opening 20.

[0059] Although the present invention has been described in relation to particular embodiments thereof, many other variations and modifications and other uses will become apparent to those skilled in the art. It is preferred, therefore, that the present invention be limited not by the specific disclosure herein, but only by the appended claims.

Claims

WHAT IS CLAIMED IS:

1. An apheresis device, comprising: a chamber; and a screen disposed inside said chamber and separating said chamber into a first space and a second space, wherein said screen includes openings that are large enough to allow passage of flexible erythrocytes from said first space into said second space but small enough to hinder passage of hard erythrocytes from said first space into said second space.

2. The device of claim 1, wherein said screen comprises a net.

3. The device of claim 1, wherein said openings are approximately 2-5 microns wide.

4. The device of claim 1, wherein said chamber includes a first opening serving as an inlet port in direct communication with said first space for deposition of whole blood containing flexible and hard erythrocytes and a second opening serving as an outlet port in direct communication with said second space for receiving whole blood with a reduced content of hard erythrocytes.

5. The device of claim 1, wherein said chamber is cylindrical.

6. The device of claim 5, wherein said screen is cylindrical, an interior of said cylindrical screen defines said first space, and said second space is defined between an exterior surface of said cylindrical screen and an interior wall of said chamber.

7. The device of claim 1, wherein said screen is a generally cylindrical body that includes an open end, an opposing closed end.

8. The device of claim 1, wherein said screen is a planar body extending from one wall of said chamber to an opposing wall of said chamber.

9. The device of claim 8, wherein said screen slopes from said one wall to said opposing wall.

10. The device of claim 1, further comprising another screen disposed within said chamber.

11. The device claim 10, wherein said screen extends from one wall of said chamber to an opposing wall of said chamber and said another screen extends from said opposing wall to said another wall of said chamber to define a third space within said chamber.

12. The device of claim 11, wherein said screen slopes from said wall to said opposing wall and said another screen slopes opposite to said slope of said screen from said opposing wall to said wall of said chamber.

13. The device of claim 12, wherein said screen slopes negatively and said another screen slopes positively.

14. The device of claim 11, wherein said chamber includes a first opening serving as an inlet port in direct communication with said first space and a second opening serving as an outlet port in direct communication with said third space.

15. An apheresis method, comprising: dividing a space into a first space and a second space using a screen; depositing a volume of whole blood containing flexible and hard erythrocytes into said first space; and removing blood that has passed through said screen to said second space; wherein said screen includes openings that are large enough to allow passage of flexible erythrocytes from said first space into said second space but small enough to hinder passage of hard erythrocytes from said first space into said second space.

16. The method of claim 15, wherein said openings are approximately 2-5 microns wide.

17. The method of claim 15, wherein said screen is comprised of a net.