System and method for extracorporeal blood filtration

Abstract

Extracorporeal organ (e.g., liver) perfusion is implemented to filter a patient's blood without direct interaction between the patient blood and the organ used for perfusion. Plasma is separated from the patient's blood and mixed with an isolated perfusate circulating in the machine perfusion system. The plasma-perfusate mixture is circulated through the organ to generate a filtered plasma-perfusate mixture. Filtered plasma is separated from the filtered plasma-perfusate mixture and reintegrated with the cell-rich patient blood, which is then circulated to the patient as filtered blood. In this way, blood components such as platelets are isolated from the organ in the machine perfusion system, while the plasma is filtered by the organ to provide removal of toxins or other waste in the patient blood.

Description

SYSTEM AND METHOD FOR EXTRACORPOREAL BLOOD FILTRATIONCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of U.S. Provisional Patent Application Serial No. 63 / 609,121, filed on December 12, 2023, and entitled “SYSTEM AND METHOD FOR EXTRACORPOREAL BLOOD FILTRATION,” which is herein incorporated by reference in its entirety.BACKGROUND

[0002] Acute liver failure (ALF) is a life-threatening condition characterized by the rapid loss of liver function due to inflammation, occurring in individuals without prior liver disease, and can lead to death within days in the absence of liver transplantation (LT). Likewise, acute-on-chronic liver failure (ACLF) represents a sudden worsening of pre-existing chronic liver disease, carrying a very high risk of death without timely LT.

[0003] Shortage of organ donors for LT often lead to fatal outcomes of the patients with ALF and ACLF. Although recovery or stabilization of ALF or ACLF can occur with nontransplant management, the complex and often fatal nature of the condition makes it difficult to predict the course. Also, rapid progression (e.g., progression in less than a few days) often does not allow for comprehensive patient assessment or the provision of appropriate medical treatment within a limited timeframe to prevent mortality without LT. Thus, absence of a method for forecasting spontaneous recoveiy without LT make the management of ALF and ACLF patients more difficult even with a risk of unnecessary LT.

[0004] To address the challenge, various extracorporeal liver assist devices, whether nonbiological dialysis-based systems or bioartificial devices that incorporate hepatocytes from various sources, have been explored to support liver function to allow LT or spontaneous recover}'. None of these methods, however, have provided a significant extension of survival.

[0005] In this context, historical case reports have shown favorable outcomes in stabilizing patients with ALF followed by LT, using extracorporeal liver perfusion (ECLP) with either human or porcine livers. ECLP distinguishes itself from other types of extracorporeal liver assist devices by employing an entire liver organ for perfusion with the patient’s blood. This approach enables the provision of biological liver functions and detoxification directly to the patient. ECLP may not support long-term survival, but can function sufficiently to support a patient through a critical period. Connected to a patient’scirculation via a catheter, these perfused livers are expected to fulfill metabolic demands, akin to extracorporeal liver assist therapy. This approach may provide additional time for thorough patient assessment and treatment. Additionally, ECLP circumvents invasive surgery and addresses donor-recipient size mismatch, especially in pediatric patients. If needed, livers can be replaced or supplemented with an additional liver for further resuscitation.

[0006] Meanwhile, normothermic machine perfusion (NMP), a technique for organ preservation, has gained increased usage in clinical LT. NMP operates by preserving the liver at body temperature with a continuous flow of perfusate and oxygenated red blood cells (RBCs), enabling the liver to sustain its metabolic activity.

[0007] Current machine perfusion technology can maintain liver graft viability for up to a week. Consequently, the technological challenges associated with ECLP could potentially be addressed by incorporating NMP technology into ECLP systems. However, the availability of human livers for ECLP is constrained by the existing organ shortage for liver transplantation, a critical issue for patients with liver diseases. As a result, the use of porcine livers presents a viable alternative.

[0008] The use of porcine organs in human organ transplantation is emerging as a practical alternative in certain areas, such as kidney and heart transplants. This advancement has been facilitated by the removal of alpha-Gal xeno-antigens and the inactivation of retroviruses. Despite these developments, the use of porcine livers for xenotransplantation faces a significant, yet unresolved challenge: the rapid and severe depletion of platelets, which can result in life-threatening bleeding complications. Furthermore, liver failure commonly leads to thrombocytopenia, a condition linked with increased bleeding risks. Thus, when porcine liver perfusion is used, this thrombocytopenia can be exacerbated, further elevating the bleeding hazards in patients with ALF and ACLF. Notably, thrombocytopenia induced by porcine liver perfusion remains a significant, unresolved challenge in considering xenotransplantation for LT.

[0009] As such, there remains a need for methods and systems to temporarily support patient liver function, while patients wait for liver transplants.SUMMARY OF THE DISCLOSURE

[0010] It is an aspect of the present disclosure to provide a method for machine perfusion. The method includes receiving plasma separated from patient blood and forming a plasma-perfusate mixture by mixing the plasma with a perfusate in a blood circuit of a machineperfusion system containing an organ. A filtered plasma-perfusate mixture is formed by perfusing the organ in the machine perfusion system with the plasma-perfusate mixture, and filtered plasma is separated from the filtered plasma-perfusate mixture. The filtered plasma is then mixed with the patient blood to form filtered patient blood.

[0011] It is another aspect of the present disclosure to provide a method for filtering a patient’s blood using a machine perfusion system. The method includes receiving patient blood from a patient at a separation circuit that includes a first plasma separator and a second plasma separator. The patient blood is routed to the first plasma separator of the separation circuit, outputting separated plasma from a first outlet of the first plasma separator and cell-rich patient blood from a second outlet of the first plasma separator. The separated plasma is routed from the first outlet of the first plasma separator to a machine perfusion system containing an organ where the separated plasma is mixed with a perfusate and circulated through the organ to form a filtered plasma-perfusate mixture. The filtered plasma-perfusate mixture is received from the machine perfusion system at the separation circuit and the filtered plasma-perfusate mixture is routed to the second plasma separator, outputting filtered plasma from a first outlet of the second plasma separator and separated perfusate from a second outlet of the second plasma separator. Filtered patient blood is formed by mixing the filtered plasma output from the first outlet of the second plasma separator with the cell-rich patient blood output from the second outlet of the first plasma separator.

[0012] It is still another aspect of the present disclosure to provide a blood filtration system that includes a first plasma separator to separate plasma from patient blood, a machine perfusion system to receive the plasma from the first plasma separator and to filter the plasma, and a second plasma separator to receive filtered plasma from the machine perfusion system and reintroduce the filtered plasma with the patient blood.

[0013] It is yet another aspect of the present disclosure to provide a method for treating a patient with liver failure. The method includes separating plasma from a patient’s blood; providing the plasma to an extracorporeal liver perfusion (ECLP) system, where the plasma is combined with a perfusate circulating in the ECLP system to form a plasma-perfusate mixture that is filtered by a liver in the ECLP system; separating filtered plasma from the plasmaperfusate mixture; and reintegrating the filtered plasma with the patient’s blood.BRIEF DESCRIPTION OF THE DRAWINGS

[0014] FIG. 1 is a schematic view of an extracorporeal blood filtration system according to a configuration of the present disclosure.

[0015] FIG. 2A is a schematic view of a reservoir used by a machine perfusion system and having two compartments according to some embodiments described in the present disclosure.

[0016] FIG. 2B is a schematic view of two reservoirs used by a machine perfusion system according to some embodiments described in the present disclosure.

[0017] FIG. 3 illustrates an example organ chamber that can contain and fluidically couple an organ to an extracorporeal blood filtration system.

[0018] FIG. 4 illustrates an example process of harvesting a porcine liver, connecting the vascular components of the porcine liver to the inlet and outlet ports of an organ chamber, transporting the organ chamber to a clinical site, and fluidically coupling the organ chamber and vascularly connected porcine liver to an extracorporeal blood filtration system.

[0019] FIG. 5 is an example method for operating an extracorporeal blood filtration system in accordance with the present disclosure.

[0020] FIG. 6 is another example method for operating an extracorporeal blood filtration system in accordance with the present disclosure.

[0021] FIG. 7 is still another example method for operating an extracorporeal blood filtration system in accordance with the present disclosure.

[0022] FIG. 8 is yet another example method for operating an extracorporeal blood filtration system in accordance with the present disclosure.DETAILED DESCRIPTION

[0023] Described here are systems and methods for filtering a patient’s blood using machine perfusion, such as extracorporeal liver perfusion, in which only the plasma from the patient’s blood is exchanged with the machine perfusion system. Advantageously, this allows detoxification and other filtering of the patient’s blood using machine perfusion, but without the patient’s whole blood directly interacting with the machine perfusion system. As an example described below in more detail, this approach allows for the detoxification benefits of porcine liver perfusion without the risk of the patient’s blood cells directly interacting with the porcine liver tissue, which can cause depletion of platelets. The present disclosure thus relates to an extracorporeal system configured to filter waste from a patient’s blood by exchangingonly the plasma from the patient’s blood with a machine perfusion system. In some implementations, the systems and methods are provided for utilizing an extracorporeal liver to filter the blood of patients experiencing liver failure. Utilizing the extracorporeal liver may prolong the life of a patient that may be waiting for a liver transplant.

[0024] As discussed above, few viable methods exist for maintaining the health of patients waiting for a liver transplant. The present disclosure provides a method and system for filtering toxins from a bloodstream of a patient. More specifically, the system and method described below utilizes an extracorporeal liver to aid or replace the function of a diseased or failed patient liver. As described below, the extracorporeal liver utilized by the system may be non-human (e.g., porcine). Utilizing non-human extracorporeal liver to filter the blood of the patient may potentially solve issues related to the availability of functioning human livers. The system and method may therefore provide necessary liver functions to patients waiting for liver transplants. The system and method may also provide necessary liver functions to patients waiting for their liver to heal or otherwise regain functionality.

[0025] A described above, known complication of utilizing non-human livers to filter human blood is thrombocytopenia. While the underlying biological mechanism of thrombocytopenia is not fully understood, experimental data suggest that this condition is driven by the phagocytosis (engulfment) of human platelets by porcine liver cells, including liver sinusoidal endothelial cells and Kupffer cells. Therefore, the disclosed systems and methods overcome this challenge in using porcine liver for machine perfusion by preventing direct contact between the patient’s blood cells, including platelets, and porcine liver cells during ECLP. As a result, the disclosed systems and methods avert platelet depletion caused by phagocytosis from porcine livers. The system described below may therefore utilize one or more plasma separators to remove human blood cells from the blood traveling from the patient to the non-human liver.

[0026] The system described below may deliver patient fluids (e.g., blood plasma) to an extracorporeal liver disposed in a normothermic machine perfusion (NMP). The liver may be configured to filter toxins from the fluids. In some non-limiting example, a first plasma separator may separate human blood cells (e.g., red blood cells, white blood cells, and platelets) from the patient plasma, prior to the introduction of the plasma to the machine perfusion system and the non-human liver. The non-human liver may then filter the plasma without harm to the blood cells of the patient.

[0027] As a general example, blood from a patient with liver failure is routed to a plasma separator where plasma is separated from blood cells including platelets. The plasma, now devoid of blood cells, is received by a machine perfusion system, such as a normothermic machine perfusion (NMP) system. The plasma is combined or otherwise mixed with perfusate, which contains oxygenated red blood cells (RBCs), in the machine perfusion circuit and then circulated through a porcine liver. Here, the liver performs its natural detoxification and metabolic functions on the plasma from the patient, which has been combined or otherwise mixed with the perfusate in the machine perfusion circuit. After treatment through the porcine liver, the plasma-perfusate mixture is subsequently filtered through another plasma separator, which separates the filtered plasma from the plasma-perfusate mixture. The filtered plasma is then reintegrated with the patient’s cellular-rich blood, while the perfusate RBCs recycle back into the NMP circuit.

[0028] In use, the patient’s cellular elements, including platelets, flow through an isolated loop. The RBCs in the NMP perfusate also circulate within a different loop inside the NMP system, partitioned from the patient’s blood by the dual plasma separators. This configuration prevents the patient’s blood cells from coming into direct contact with the porcine liver, mitigating the risk of platelet depletion and bleeding complications. This system allows for the detoxification benefits of porcine liver perfusion without the risk of the patient’s blood cells directly interacting with the porcine liver tissue.

[0029] FIG. 1 illustrates a non-limiting example of a blood filtration system 100 that is configured to filter patient blood. As described above, the blood filtration system 100 receives patient blood 108 from a patient 112 and separates plasma 132 from the patient blood 108 thereby leaving cell-rich patient blood 138 in the patient blood circuit. The separated plasma 132 is then mixed or otherwise combined with a perfusate 155 circulating in a machine perfusion system 148 to form a plasma-perfusate mixture 156, which is used to perfuse an organ 116 (e.g., an extracorporeal liver, such as a porcine liver) by circulating the plasmaperfusate mixture 156 through the organ 116. Filtered plasma 133 (i.e., plasma that has been filtered after the plasma-perfusate mixture 156 has circulated through the organ 116) is separated from the plasma-perfusate mixture 156 and then mixed or otherwise combined with the cell-rich patient blood 138 to form filtered patient blood 110 that is reintroduced to the patient 112.

[0030] The blood filtration system 100 includes one or more pumps configured to pump patient blood 108 (e.g., whole blood) from a patient 112 toward the machine perfusion system148 for filtration. The one or more pumps may be any kind of pump configured to pump fluid. The pumps may advantageously mitigate cavitation in the blood and blood plasma, for example the pumps may be a displacement pump (e.g., a roller pump), a rotary pump (e.g., a centrifugal pump), or the like.

[0031] As an illustrative example, the blood filtration system 100 may include a first pump 120 to pump the patient blood 108 from the patient 112 to a separation circuit 124. The separation circuit 124 generally includes a first plasma separator 128 to separate plasma 132 from the patient blood 108 and a second plasma separator 150 to separate filtered plasma 133 from the plasma-perfusate mixture 156 circulating within the machine perfusion system 148.

[0032] The first plasma separator 128 and second plasma separator 150 may be any plasma separator configured to separate plasma from the blood, such as a hollow fiber plasma separator. In general, a hollow fiber plasma separator includes a semipermeable membrane that separates and removes plasma from blood, simultaneously replacing the removed plasma with an appropriate fluid. For instance, the hollow fiber plasma separator may include a permeable hollow fiber membrane. In some embodiments, the hollow fiber membrane may have a sieving coefficient that is sufficient to separate protein components with low blood cell loss, including platelets. Hollow fiber membranes can advantageously allow for efficient separation of plasma while maintaining the integrity of other blood components. Thus, the first plasma separator 128 can separate the patient blood 108 into plasma 132 and cell-rich patient blood 138, and the second plasma separator 150 can separate the plasma-perfusate mixture 156 into filtered plasma 133 and perfusate 155. The plasma separators 128, 150 may separate all or some of the plasma from the input blood, or may separate only a percentage of the plasma, such as between about 10% and about 60% of the plasma, from the input blood .

[0033] The first plasma separator 128 may include one or more ports configured to receive and convey the patient blood 108. The first plasma separator 128 may receive the patient blood 108 through an inlet port 136. The first plasma separator 128 may separate the patient blood 108 and convey separated cell-rich patient blood 138 and the plasma 132 to a blood outlet port 140 and a plasma outlet port 144, respectively. The first plasma outlet port 144 may be connected to a machine perfusion system 148to introduce the plasma 132 to the machine perfusion system 148.

[0034] The machine perfusion system 148 generally includes a perfusate 155 circulating in a machine perfusion circuit. The perfusate includes oxygenated RBCs. The perfusate is advantageously isolated from the patient blood 108. The plasma 132 is combinedor otherwise mixed with the perfusate to form a plasma-perfusate mixture 156 that circulates through the machine perfusion circuit. For instance, the plasma-perfusate mixture 156 is routed to a reservoir 166.

[0035] The machine perfusion system 148 includes a reservoir 166 that receives plasma-perfusate mixture 156 from the separation circuit 124. A second pump 152 pumps the plasma-perfusate mixture 156 from the reservoir 166 to the organ 116 (e.g., extracorporeal liver, such as a porcine liver) to perfuse the organ 116 with the plasma-perfusate mixture 156. The plasma-perfusate mixture 156 that has circulated through the organ 116 is then returned to the reservoir 166. In some embodiments, the reservoir 166 may include a single volume in which plasma-perfusate mixture 156 from the separation circuit 124 and organ 116 are allowed to mix. In some other embodiments, such as those shown in FIG. 2A, the reservoir 166 may include separate compartments or chambers: one for receiving plasma-perfusate mixture 156 from the separation circuit 124 and one for receiving the filtered plasma-perfusate mixture 156 from the organ 116. In still other embodiments, such as those shown in FIG. 2B, more than one reservoir may be used (e.g., one reservoir for receiving the plasma-perfusate mixture 156 from the separation circuit 124 and one reservoir for receiving the plasma-perfusate mixture 156 from the organ 116).

[0036] The blood filtration system 100 may include a third pump 174 to pump the plasma-perfusate mixture 156 from the reservoir 166 to the separation circuit 124, or alternatively to pump filtered plasma-perfusate mixture 156 from a separate compartment of the reservoir 166 to deliver the filtered plasma-perfusate mixture 156 to the separation circuit 124. The plasma-perfusate mixture 156 received by the separation circuit 124 from the machine perfusion system 148 is routed to the second plasma separator 150. For instance, the plasmaperfusate mixture 156 may be received at an inlet port 154 of the second plasma separator 150. The separated, filtered plasma 133 may then exit the second plasma separator 150 via a plasma outlet port 162 and the perfusate 155 may exit the second plasma separator 150 via a perfusate outlet port 158.

[0037] The second plasma separator 150, may be any plasma separator configured to separate the filtered plasma 133 from the plasma-perfusate mixture 156. For example, as described above, the second plasma separator 150 may be a hollow fiber plasma separator. In some configurations, the first plasma separator 128 and the second plasma separator 150 may be configured to separate a similar amount of plasma from the patient blood 108 and the plasma-perfusate mixture 156, respectively.

[0038] As described above, the filtered plasma 133 received from the second plasma separator 150 is mixed or otherwise combined with the cell-rich blood 138 that is output from the first plasma separator 128 to reintegrate the filtered plasma 133 with the cell-rich blood 138. The resultant filtered patient blood 110 is then circulated back to the patient 112, thereby at least partially replacing the function of the failing or failed liver of the patient 112.

[0039] In some configurations, the separation circuit 124 may be a parallel circuit, such that the first plasma separator 128 and the second plasma separator 150 are connected in parallel. In some configurations, the blood outlet port 140 of the first plasma separator 128 may be connected to the plasma outlet port 162 of the second plasma separator 150. The connection of the blood outlet port 140 and the plasma outlet port 162 allows for the filtered plasma 133 and the cell-rich patient blood 138 to mix prior to being introduced to the patient 112. The filtered plasma 133 and the cell-rich patient blood 138 may mix to form the filtered patient blood 110.

[0040] In some configurations, the blood outlet port 158 of the second plasma separator 150 may be connected to the plasma outlet port 144 of the first plasma separator 128. The connection of the blood outlet port 158 and the plasma outlet port 144 allows the plasma 132 and the perfusate 155 to mix prior to being introduced to the reservoir 166 of the machine perfusion system 148. The plasma 132 and the perfusate 155 may mix to form the plasmaperfusate mixture 156.

[0041] As described above, the machine perfusion system 148 includes an organ 116 that is perfused by the plasma-perfusate mixture 156. The organ may be a liver, a kidney, or the like. As an illustrative example, the organ 116 may be a liver from any animal type (e.g., human, pig, sheep, or the like). The liver may advantageously be porcine due to a greater availability of healthy pig liver. The plasma-perfusate mixture 156 circulated through the organ 116 may be filtered by the organ 116. For example, the organ 116 may be a liver that breaks down and removes toxins and waste from the plasma contained in the plasma-perfusate mixture 156.

[0042] In some embodiments, the organ 116 may be provided to the blood filtration system 100 via an organ chamber that allows for simpler fluid coupling of the organ 116 to the other components of the blood filtration system 100 (e.g., pumps, reservoirs, etc.). For example, as illustrated in FIG. 3, the organ 116 can be housed in an organ chamber 180 that is constructed as a housing 182 having a base 184, side walls 186, and a top 188. The top 188 may be, for instance, a lid that allows for opening and closing the housing 182 to provide access to theinterior volume of the organ chamber 180 for placing and removing the organ 116 from the organ chamber 180. In other embodiments, the housing 182 may not have atop 188, such that the interior volume of the organ chamber is always accessible by a user.

[0043] The organ chamber 180 also includes a tubing system that includes an inlet 190 and an outlet 192 for fluidi cally coupling the organ 116 to one or more components of the blood filtration system 100. The inlet 190 and the outlet 192 can pass through respective openings in a side wall 186 of the housing 182. When the organ 116 is placed within the interior volume of the housing 182, the tubing 190 and the outlet 192 can be fluidi cally coupled to the organ 116. For example, the inlet 190 can be coupled to a vascular component of the organ 116 (e.g., an artery, a vein) via an inlet tubing 194 and the outlet 192 can be coupled to another vascular component of the organ 116 (e.g., another artery, another vein) via an outlet tubing 196. By fluidically coupling the organ 116 to the inlet 190 and the outlet 192, subsequently connecting the organ chamber 180 to the blood filtration system 100 results in the organ 116 being fluidically coupled to the components of the blood filtration system 100 via the inlet 190 and the outlet 192. For example, the inlet 190 can fluidically couple the organ 116 to a pump (e.g., the second pump 152 that pumps the plasma-perfusate mixture 156 from the reservoir 166 to the organ 116) and the outlet 192 can fluidically couple the organ 116 to a reservoir (e.g., reservoir 166).

[0044] The organ chamber 180 allows for safe transport of the organ 116 and also for the organ 116 to be quickly and efficiently introduced into the blood filtration system 100. As illustrated in FIG. 4, the organ 116 can be placed within the organ chamber 180 at a remote site (e.g., shortly after the organ 116 has been harvested). The organ 116 can then be fluidically coupled to the tubing system of the organ chamber 180 by coupling one end of the inlet tubing 194 to a vascular component in the organ (e.g., an artery, a vein) and the other end of the inlet tubing 194 to the inlet 190. Similarly, one end of the outlet tubing 196 may be coupled to another vascular component in the organ (e.g., a second artery, a second vein) and the other end of the outlet tubing 196 may be coupled to the outlet 192. The organ chamber 180 can then be transported to the clinical site where the blood filtration system 100 resides, where the organ chamber 180 is then coupled to the blood filtration system 100 by connecting the inlet 190 and outlet 192 of the organ chamber 180 to the respective components of the blood filtration system 100.

[0045] Referring now to FIG. 5, a method 500 is illustrated for filtering blood utilizing an extracorporeal blood filtration system, which may include fewer or more steps than depicted.In some embodiments, the following steps are performed in any order. At a first step 504, the method 500 includes receiving patient blood at a separation circuit. At a second step 508, the method 500 includes at least partially separating the patient blood into plasma and separated cell-rich patient blood. At a third step 512, the method 500 includes filtering the plasma in a machine perfusion system. At a fourth step 516, the method 500 includes reintroducing the now-filtered filtered plasma into the cell-rich patient blood, which is then circulated through the patient.

[0046] Referring now to FIG. 6, a method 600 is illustrated for filtering blood utilizing an extracorporeal blood filtration system, which may include fewer or more steps than depicted. In some embodiments, the following steps are performed in any order. At a first step 604, the method 600 includes providing a patient, a plurality of plasma separators, a plurality of pumps, an organ (e.g., a liver), and a machine perfusion system. At a second step 608, the method 600 includes extracting and at least partially separating blood of the patient into plasma and separated cell-rich patient blood. At a third step 612, the method 600 includes pumping the plasma to the machine perfusion system. At a fourth step 616, the method 600 includes filtering the plasma utilizing the organ in the machine perfusion system. At a fifth step 620, the method 600 includes reintroducing the now filtered plasma into the cell-rich patient blood, which is then circulated back through the patient.

[0047] Referring now to FIG. 7, a method 700 is illustrated for filtering blood utilizing an extracorporeal blood filtration system, which may include fewer or more steps than depicted. In some embodiments, the following steps are performed in any order. At a first step 704, the method 700 includes providing a patient, a plurality' of plasma separators, a plurality of pumps, one or more reservoirs, an organ (e.g., a liver), and a machine perfusion system. At a second step 708, the method 700 includes pumping patient blood from the patient to a first plasma separator. At a third step 712, the method 700 includes at least partially separating the patient blood into plasma and separated cell-rich patient blood. At a fourth step 716, the method 700 includes mixing the plasma with perfusate in the machine perfusion system to form a plasmaperfusate mixture. At a fifth step 720, the method 700 includes storing the plasma-perfusate mixture in a reservoir. At a sixth step 724, the method 700 includes pumping the plasmaperfusate mixture from the reservoir to the organ. At a seventh step 728, the method 700 includes filtering the plasma-perfusate mixture using the organ. At an eighth step 732, the method 700 includes receiving the filtered plasma-perfusate mixture in the reservoir. At a ninth step 736, the method 700 includes pumping the filtered plasma-perfusate mixture from thereservoir to a second plasma separator. At a tenth step 740, the method 700 includes at least partially separating the filtered plasma-perfusate mixture into plasma and the separated perfusate. At an eleventh step 744, the method 700 includes mixing the plasma with the separated cell-rich patient blood to form filtered patient blood. At a twelfth step 748, the method 700 includes introducing the filtered patient blood to the patient.

[0048] Referring now to FIG. 8, a method 800 is illustrated for filtering blood utilizing an extracorporeal blood filtration system, which may include fewer or more steps than depicted. In some embodiments, the following steps are performed in any order. At a first step 804, the method 800 includes providing a patient, a plurality of plasma separators, a plurality of pumps, one or more reservoirs, an organ (e.g., a liver), and a machine perfusion system. At a second step 808, the method 800 includes pumping patient blood from the patient to a first plasma separator. At a third step 812, the method 800 includes at least partially separating the patient blood into plasma and separated cell-rich patient blood. At a fourth step 816, the method 800 includes mixing the plasma with perfusate circulating the machine perfusion system to form a plasma-perfusate mixture. At a fifth step 820, the method 800 includes storing the plasmaperfusate mixture in a first reservoir. At a sixth step 824, the method 800 includes pumping the plasma-perfusate mixture from the first reservoir to the organ in the machine perfusion system. At a seventh step 828, the method 800 includes filtering the plasma-perfusate mixture using the organ. At an eighth step 832, the method 800 includes receiving the filtered plasmaperfusate mixture in a second reservoir. At a ninth step 836, the method 800 includes pumping the filtered plasma-perfusate mixture from the second reservoir to a second plasma separator. At a tenth step 840, the method 800 includes at least partially separating the filtered plasmaperfusate mixture into filtered plasma and the separated perfusate. At an eleventh step 844, the method 800 includes mixing the filtered plasma with the separated cell-rich patient blood to form filtered patient blood. At a twelfth step 848, the method 800 includes introducing the filtered patient blood to the patient.

[0049] It is to be understood that the systems and methods described in the present disclosure are not limited in their application to the details of construction and the arrangement of components set forth in the preceding description or illustrated in the drawings. The disclosed systems and methods are capable of other embodiments and of being practiced or of being carried out in various ways. Also, it is to be understood that the phraseology and terminology used herein is for the purpose of description and should not be regarded as limiting. The use of “including,” “comprising,” or “having” and variations thereof herein ismeant to encompass the items listed thereafter and equivalents thereof as well as additional items. Unless specified or limited otherwise, the terms “mounted,” “connected,” “supported,” and “coupled” and variations thereof are used broadly and encompass both direct and indirect mountings, connections, supports, and couplings. Further, “connected” and “coupled” are not restricted to physical or mechanical connections or couplings, and may also include fluid and electrical connections.

[0050] One or more embodiments are described and illustrated in the preceding description and accompanying drawings. These embodiments are not limited to the specific details provided herein and may be modified in various ways. Further, other embodiments may exist that are not expressly described herein. Also, functions described as being performed by multiple components may be consolidated and performed by a single component. Similarly, functions described herein as being performed by one component may be performed by multiple components in a distributed manner. Additionally, a component described as performing particular functionality may also perform additional functionality not expressly described herein. For example, a device or structure that is “configured” in a certain way is configured in at least that way, but may also be configured in ways that are not expressly listed.

[0051] The present disclosure has described one or more preferred embodiments, and it should be appreciated that many equivalents, alternatives, variations, and modifications, aside from those expressly stated, are possible and within the scope of the invention.

Claims

CLAIMS1. A method for machine perfusion, comprising: receiving plasma separated from patient blood; forming a plasma-perfusate mixture by mixing the plasma with a perfusate in a blood circuit of a machine perfusion system containing an organ; forming a filtered plasma-perfusate mixture by perfusing the organ in the machine perfusion system with the plasma-perfusate mixture; separating filtered plasma from the filtered plasma-perfusate mixture; and mixing the filtered plasma with the patient blood to form filtered patient blood.

2. The method of claim 1, wherein the organ is a liver.

3. The method of claim 2, wherein the liver is a porcine liver.

4. The method of claim 1, wherein the machine perfusion system comprises a normothermic machine perfusion system.

5. The method of claim 1, wherein the filtered plasma is separated from the filtered plasma-perfusate mixture using a plasma separator.

6. The method of claim 1, wherein receiving the plasma separated from the patient blood comprises: receiving the patient blood at a plasma separator; and separating the patient blood into the plasma and cell-rich patent blood using the plasma separator.

7. A method for filtering a patient’s blood using a machine perfusion system, the method comprising: receiving patient blood from a patient at a separation circuit comprising a first plasma separator and a second plasma separator; routing the patient blood to the first plasma separator of the separation circuit, outputting separated plasma from a first outlet of the first plasma separator and cell-rich patient blood from a second outlet of the first plasma separator;routing the separated plasma from the first outlet of the first plasma separator to a machine perfusion system containing an organ, wherein the separated plasma is mixed with a perfusate and circulated through the organ to form a filtered plasmaperfusate mixture; receiving the filtered plasma-perfusate mixture from the machine perfusion system at the separation circuit; routing the filtered plasma-perfusate mixture to the second plasma separator, outputting filtered plasma from a first outlet of the second plasma separator and separated perfusate from a second outlet of the second plasma separator; and forming filtered patient blood by mixing the filtered plasma output from the first outlet of the second plasma separator with the cell-rich patient blood output from the second outlet of the first plasma separator.

8. The method of claim 7, wherein the organ is a liver.

9. The method of claim 8, wherein the liver is a porcine liver.

10. The method of claim 7, wherein the machine perfusion system is a normothermic machine perfusion system.

11. A blood filtration system, comprising: a first plasma separator to separate plasma from patient blood; a machine perfusion system to receive the plasma from the first plasma separator and to filter the plasma; a second plasma separator to receive filtered plasma from the machine perfusion system and reintroduce the filtered plasma with the patient blood.

12. The blood filtration system of claim 11, wherein the machine perfusion system comprises: an organ chamber; and a reservoir fluidically coupled to the organ chamber, the first plasma separator, and the second plasma separator.

13. The blood filtration system of claim 12, wherein the reservoir contains a perfusate and the reservoir receives the plasma from the first plasma separator to mix the plasma with the perfusate thereby forming a plasma-perfusate mixture.

14. The blood filtration system of claim 13, further comprising a first pump to pump the plasma-perfusate mixture from the reservoir to an inlet of the organ chamber, thereby returning a filtered plasma-perfusate mixture to the reservoir.

15. The blood filtration system of claim 14, further comprising a second pump to pump the filtered plasma-perfusate mixture from the reservoir to the second plasma separator to separate filtered plasma from the perfusate and return the perfusate to the reservoir.

16. The blood filtration system of claim 12, wherein the organ chamber comprises a housing, an inlet, and an outlet, wherein the inlet and the outlet fluidically couple the organ chamber to the reservoir.

17. The blood filtration system of claim 16, wherein the organ chamber contains an organ having a first vascular component coupled to the inlet and a second vascular component coupled to the outlet.

18. The blood filtration system of claim 17, wherein the organ is a liver.

19. The blood filtration system of claim 18, wherein the liver is a porcine liver.

20. A method for treating a patient with liver failure, the method comprising: separating plasma from a patient’s blood; providing the plasma to an extracorporeal liver perfusion (ECLP) system, wherein the plasma is combined with a perfusate circulating in the ECLP system to form a plasma-perfusate mixture that is filtered by a liver in the ECLP system; separating filtered plasma from the plasma-perfusate mixture; and reintegrating the filtered plasma with the patient’s blood.

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