Abstract
A device for removing noxae from blood, in an extracorporeal perfusion system, includes a housing and a plurality of hollow fibers provided inside the housing, which can be perfused by the blood. The hollow fibers each have a plurality of pores that permit the plasma of the blood to flow through the pores from an inside of the hollow fibers to an outside of the hollow fibers. The hollow fibers are modified or pretreated, in particular chemically, in such a way that they have a functionalized surface which binds the noxae to itself and removes the noxae from the blood. An inside surface of the hollow fibers includes a coating, in particular a hemocompatible and anticoagulant coating, which is arranged to prevent damage to the cellular components of the blood when the blood flows through the hollow fibers. An extracorporeal perfusion system includes the device.
Claims
1. A device for removing noxae from blood which comprises plasma and cellular components in an extracorporeal perfusion system, comprising: a housing and a plurality of hollow fibers provided inside the housing and configured to be perfused by the blood, wherein the hollow fibers each have a plurality of pores configured such that the plasma of the blood can flow through the pores from an inside of the hollow fibers to an outside of the hollow fibers, and wherein the hollow fibers are modified or pretreated in such a way that they have a functionalized surface which binds the noxae to itself and removes the noxae from the blood, wherein an inside surface of the hollow fibers is further provided with a coating which is configured to prevent damage of the cellular components of the blood when the blood flows through the hollow fibers.
2. The device according to claim 1, wherein the coating is arranged or formed on the inside surface of the hollow fibers in such a way that the inner circumferential sides of the pores are not covered or incompletely covered by the coating.
3. The device according to claim 1, wherein the coating on the inside surface of the hollow fibers is both hemocompatible and anticoagulant as well as compatible with the functionalized surface of the hollow fibers which binds the noxae to itself and removes them from the blood, and to which the coating is applied on the inside surface of the hollow fibers.
4. The device according to claim 1, wherein the coating is applied to the inside surface of the hollow fibers by causing a solution to flow through the hollow fibers.
5. The device according to claim 4, wherein the solution is a negatively charged anionic solution.
6. The device according to claim 4, wherein the coating is only applied to the inside surface of the hollow fibers and a saturation of the inside surface of the hollow fibers with the solution is achieved, and a thickness of the coating is varied by adjusting a quantity, a flow rate and an anion concentration of the solution.
7. The device according to claim 4, wherein the housing is closed on an outlet side when the solution is introduced into the hollow fibers.
8. An extracorporeal perfusion system comprising a device for removing noxae from blood according to claim 1 and a pump which conveys the plasma of the blood out of the hollow fibers via the pores and feeds it back downstream of the device to the blood which has flowed through the device.
9. A method for producing a device for removing noxae from blood comprising the steps: a) producing a plurality of porous hollow fibers; b) modifying or pretreating the hollow fibers in such a way that they have a functionalized surface which binds the noxae to itself and removes the noxae from the blood; c) inserting said plurality of porous hollow fibers into a housing; and d) causing a solution to flow through the plurality of porous hollow fibers located in the housing; the method steps a) to d) being carried out in chronological order.
10. The method according to claim 9, further comprising the step: e) adjusting a quantity and a flow rate of the solution; wherein method step e) is carried out before method step d).
11. The method according to claim 9, further comprising the step: f) closing the housing on an outlet side before the solution is introduced into the hollow fibers.
Description
BRIEF DESCRIPTION OF THE DRAWING FIGURES
[0044] The present disclosure is further explained below with the help of Figures wherein:
[0045] FIG. 1 shows a schematic view of an extracorporeal perfusion system according to the present disclosure;
[0046] FIG. 2 shows a perspective view of a device according to the present disclosure for the removal of noxae from blood;
[0047] FIG. 3 shows a perspective side view of the device according to the present disclosure;
[0048] FIG. 4 shows a schematic sectional view of the device according to the present disclosure;
[0049] FIG. 5 shows a perspective view of a hollow fiber provided in the device;
[0050] FIG. 6 shows a schematic view of the hollow fiber;
[0051] FIG. 7 shows a schematic sectional view of the hollow fiber in which a blood treatment known from prior art is illustrated;
[0052] FIG. 8 shows a schematic sectional view of the hollow fiber in which a blood treatment according to the present disclosure is illustrated; and
[0053] FIG. 9 shows a flowchart of the method according to the present disclosure.
[0054] The Figures are merely schematic in nature and serve exclusively to understand the present disclosure. Identical elements are provided with the same reference signs.
DETAILED DESCRIPTION
[0055] FIG. 1 shows a schematic view of an extracorporeal perfusion system 2 according to the present disclosure comprising a device 4 for the removal of noxae from blood. In this method, blood is taken from a human 6, which is pumped by means of a first pump 10 via a first line 8 to the device 4. The device 4 comprises, as shown in FIG. 2, a housing 12 and a multitude of hollow fibers 14 located inside the housing 12. The blood is essentially supplied to the hollow fibers 14. The hollow fibers 14 are porous, so that the plasma of the blood (blood plasma) can at least partly be sucked/pumped by means of a second pump 16 out of the device 4 and into a second line 18. At least the cellular components of the blood, such as erythrocytes, leukocytes or thrombocytes, leave the device 4 via a third line 20. Downstream of the device 4, the second line 18 and the third line 20 converge again and the blood is returned to the human 6 via a fourth line 22. In the extracorporeal perfusion system 2 according to the present disclosure, the blood with all its components, i.e. in particular both with plasma and blood cells, is fed to the device 4. No separate plasma separator is required to separate the plasma from the blood cells. The device 4 is designed to clean the blood and remove noxae from the blood. A shut-off valve 24 is provided on the outlet side of the device 4 at the beginning of the third line 20.
[0056] FIG. 2 shows a perspective view of the device 4 according to the present disclosure, comprising a housing 12 and a plurality of hollow fibers 14 located within the housing 12. The housing 12 has an essentially tube-like/tubular/cylindrical shape. A first port 26 is provided on the outer peripheral surface of the housing 12 near an inlet side of the housing 12 and a second port 28 is provided near an outlet side of the housing 12. The second line 18 shown in FIG. 1 can be connected to the first port 26 and/or to the second port 28 in order to convey the plasma of the blood out of the device 4 by means of the second pump 16.
[0057] FIG. 3 shows a perspective side view of the device 4 according to the present disclosure. In the view shown in FIG. 3, the device 4 is covered on the inlet side by a first cover cap 30 and on the outlet side by a second cover cap 32. The cover caps 30, 32 are of identical design and are adapted in shape and size to the round/circular inlet or outlet of the housing 12.
[0058] FIG. 4 shows a schematic sectional view of the device 4 according to the present disclosure, taken along the section line A-A shown in FIG. 3. In the view shown in FIG. 4, the hollow fibers 14 are shown slightly enlarged in order to illustrate the arrangement of the hollow fibers 14 within the housing 12 better than is the case in FIG. 2. The plurality of hollow fibers 14 extend in the longitudinal/axial direction of the substantially tubular/cylindrical housing 12 and fill substantially the entire interior space defined by the housing 12 (see also FIG. 2). The entirety of the hollow fibers 14 fauns a hollow fiber membrane.
[0059] FIG. 5 shows an enlarged perspective view of a single hollow fiber 14 provided in the device 4. The base material of the hollow fiber 14 is preferably polyamide on which diethylaminoalkyl or diethylaminoaryl is grafted in tentacular fashion (not shown). As indicated in FIG. 5, the hollow fibers 14 are porous.
[0060] FIG. 6 shows a schematic view of the hollow fiber 14, in which the porous structure is represented by a plurality of enlarged pores 34. FIG. 7 and FIG. 8 are sectional views of the hollow fiber 14 shown in FIG. 6, taken at the section line B-B shown in FIG. 6.
[0061] The core aspects of this present disclosure are explained using FIG. 7 and FIG. 8. FIG. 7 illustrates a blood treatment known from the prior art of EP 1 602 387 A1 and FIG. 8 shows a blood treatment according to the present disclosure.
[0062] The hollow fiber 14 shown in FIG. 7 has a functionalized surface 36. The functionalized surface 36 is positively charged and is designed to bind noxae 38 to itself which are found in the blood 44 and to remove them from the blood 44. The functionalized surface 36 is provided both on an inside surface 40 of the hollow fiber 14 and an outside surface 42 of the hollow fiber 14 as well as in the area of the pores 34. The functionalized surface 36 is produced by a chemical modification, in particular by graft polymerization.
[0063] If now blood 44, which has blood plasma 46 and blood cells 48, flows through the hollow fiber 14 shown in FIG. 7, the negatively charged noxae 38 located in the blood 44 and in particular in the blood plasma 46 are bound to the positively charged (surface of the) hollow fiber 14 both on the inside surface 40 and outside surface 42 as well as in the area of the pores 34 and are thus removed from the blood. The size or diameter of the pores 34 is such that the blood cells 48 cannot flow through the pores 34. If the blood cells 48 shown in FIG. 7 come into contact with the functionalized surface 36, the blood cells 48 are damaged/destroyed, as indicated by a flash in FIG. 7. In the prior art, the blood cells 48 must therefore be separated from the blood plasma 46 so that the blood cells 48 do not enter the device 4 or the hollow fibers 14.
[0064] According to the present disclosure, the inside surface 40 of the hollow fibers 14 is further provided with a hemocompatible and anticoagulant coating 50 (see FIG. 8). The coating 50 is applied by causing a flow of a negatively charged anionic solution (e.g. an anticoagulant polyanion such as heparin) through the hollow fibers 14 (before the blood treatment shown). This ensures that, on the one hand, the functionalized, positively charged surface 36 on the inside surface 40 of the hollow fibers 14 is bound/discharged/neutralized by the negatively charged anionic solution, as illustrated in FIG. 8 by the contiguous positive and negative, hence neutralizing charges on the inside surface 40 of the hollow fibers 14. On the other hand, a coating 50 binds to the (previously) functionalized surface 36. The coating 50 is hemocompatible and anticoagulant, so that the blood cells 48 flowing through the hollow fibers 14 are not damaged when they hit the inside surface 40 (indicated by a checkmark in FIG. 8). The coating 50 is compatible with the functionalized surface 36 and adheres to it.
[0065] If now blood 44, which contains blood plasma 46 and blood cells 48, flows through the hollow fiber 14 shown in FIG. 8, the negatively charged noxae 38 located in the blood 44 and in particular in the blood plasma 46 are only bound to the outside surface 42 and in the region of the pores 34 to the positively charged (surface of the) hollow fiber 14 and thus removed from the blood. No noxae 38 are bound to the inside surface 40 of the hollow fiber 14 and, as already explained, the blood cells 48 are thus not damaged. In the device 4 according to the present disclosure, it is therefore not necessary to separate the blood cells 48 from the blood plasma 46 upstream of the device 4.
[0066] By setting a flow rate and an anion concentration of the anionic solution which flows through the hollow fiber 14 before the blood treatment shown, it is possible to coat only the inside surfaces 40 of the hollow fibers 14, but not the pores 34 and the outside surfaces 42 of the hollow fibers 14. This is achieved in particular by setting the flow rate to a low value and the anion concentration to a high value (more viscous anionic solution). By adjusting the quantity of the anionic solution, a saturation of the inside surfaces 40 of the hollow fibers 14 and a thickness of the coating 50 can be adjusted.
[0067] Here it applies that the coating 50 becomes the thicker the larger the quantity/amount of liquid is which enters the hollow fibers 14.
[0068] The shut-off valve 24 shown in FIG. 1 is closed when the anionic solution is introduced into the device 4 or the multitude of hollow fibers 14.
[0069] FIG. 9 illustrates a flow chart of the method according to the present disclosure. In accordance with the method according to the present disclosure, a plurality of porous hollow fibers 14 is first produced in step S1. The hollow fibers 14 are then modified/pretreated in step S2 in such a way that they have a functionalized surface 36 which binds the noxae to itself and removes them from the blood. Then, in step S3, the plurality of porous hollow fibers 14 is inserted into a housing 12. In step S4, the housing 12 is closed on the outlet side by a valve (the shut-off valve 24) and, in parallel, a quantity, a flow rate and an anion concentration of an anionic solution are adjusted in step S5. Finally, in step S6, the anionic solution is caused to flow through the hollow fibers 14 located in the housing 12.
