dialysis filter device

Abstract

The present invention relates to a peritoneal dialysis filter device comprising a housing with a first port and a second port, and a hollow fiber membrane formed from hydrophilic hollow fibers within the housing. In use, dialysate from a subject enters the filter device through the first port and exits in an outflow direction via the second port, and regenerated dialysate from a sorbent system enters the filter device through the second port and exits in an inflow direction via the first port. Also disclosed herein are a peritoneal dialysis system, a method for controlling dialysate flow in a peritoneal dialysis system, and a hemodialysis machine comprising the filter device.

Description

[Technical Field]

[0001] The present invention relates to the field of peritoneal dialysis and hemodialysis filter devices. Also disclosed herein are dialysis systems and methods that utilize filters. [Background technology]

[0002] The listing or description of any prior-published document in this specification should not necessarily be construed as an acknowledgement that the document is part of the state of the art or is common general knowledge.

[0003] Peritoneal dialysis (PD) is a type of dialysis that uses the peritoneal membrane within the subject's abdomen as a membrane through which mass transfer of fluid and solutes occurs between the dialysate and the blood. This process is used to remove excess fluid, correct electrolyte and acid-base imbalances, and remove toxins in the treatment of patients with kidney failure.

[0004] In peritoneal dialysis, dialysate (usually a solution containing sodium chloride, sodium bicarbonate / sodium lactate, and an osmotic agent) is introduced through a permanent tube in the lower abdomen, allowed to dwell for a period of time, and then removed. This can be done at regular intervals throughout the day (known as continuous ambulatory peritoneal dialysis (CAPD)) or overnight with the assistance of a machine (known as automated peritoneal dialysis (APD)). Compared to hemodialysis, PD allows for greater patient mobility, results in less fluctuation in symptoms because of its continuous nature, and is inherently safer because it does not rely on extracorporeal circulation of the patient's blood.

[0005] However, due to the oncotic gradient in the peritoneal dialysis system, proteins excreted by the subject are transported into the subject's peritoneal membrane, where they mix with toxins and electrolytes present in the dialysate fluid. There are several problems associated with this mixing. These include: (a) this mixing leads to significant protein loss from subjects over long-term peritoneal dialysis treatment; and (b) Because of their relatively large size, proteins can become trapped inside adsorbent systems (when such systems are used to remove toxins), thereby affecting the efficiency of the adsorbent. Includes.

[0006] Additional challenges that may be encountered with conventional PD systems include, but are not limited to: (1) In sorbent-based dialysis systems, such as the REDY system, CO2 generated during dialysate regeneration can pose a health risk (hypercapnia) to patients with respiratory failure, and the accumulation of CO2 bubbles can impair the effective surface area of ​​the hollow fibers used in the REDY system, thereby reducing their performance and dialysis efficiency. In sorption dialysis, the dialysate containing urea flows through urease, where the urea is hydrolyzed to ammonium and bicarbonate. Zirconium phosphate adsorbs cations, such as ammonium ions, releasing sodium and hydrogen ions, which then react with bicarbonate to produce CO2. In closed-loop systems without active degassing (e.g., the REDY system), this can lead to the accumulation of potentially dangerous levels of pCO2 in the dialysate and return blood. While patients can usually exhale excess CO2 without apparent adverse symptoms, patients with compromised respiratory systems experience a hypercapnic, acidotic state. Thus, conventional adsorption dialysis systems do not provide an effective CO2 removal mechanism and rely on patient breathing to compensate for increased serum pCO2. Furthermore, increased dialysate pCO2 can lead to spontaneous air bubble generation, which can easily accumulate in the filter. Conventional filters in adsorption dialysis do not include provisions for bubble removal, thus requiring manual intervention to "eruct the dialyzer" (the term used) and prevent loss of dialysis surface area and underdialysis. In addition to routine kidney dialysis, CO2 removal is also a necessary and useful function for dialysis in acute care facilities (e.g., in intensive care units (ICUs)). Current treatments use separate devices to administer dialysis and to oxygenate serum / remove CO2. (2) Protein-bound uremic toxins (PBUT) have been implicated in numerous adverse effects in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD). A growing body of literature suggests that improving dialysis removal of PBUT could improve outcomes in HD / PD patients. Methods for removing PBUT in both HD and PD systems have been proposed. However, none of these methods have been validated in patients or integrated into existing equipment. One major reason for this is that many of the solutions propose adding albumin binder competitors to the dialysate solution, which alters the dialysate composition and, potentially, the patient's serum composition. Therefore, these solutions are currently considered pharmaceuticals and, as such, must undergo rigorous clinical trials and regulatory processes before they can be approved for use. (3) Proteins trapped inside the filter during dialysis can clog the filter and impair filtration by impeding the system's flow rate and reducing the surface area available for filtration. This can result in reduced therapeutic efficacy. Furthermore, in the case of infection, an increase in excreted white blood cells can similarly affect the flow path. Finally, in conventional peritoneal dialysis methods, excreted proteins are discarded with the drain fluid, resulting in significant protein loss in the patient over time. This can lead to malnutrition in subjects undergoing PD, further worsening the already impaired nutritional balance of many PD patients.

[0007] Thus, there remains a need for an improved peritoneal dialysis system that overcomes some or all of the problems identified above. Summary of the Invention

[0008] 1. A peritoneal dialysis filter device, comprising: a housing having a first port and a second port; a hollow fiber membrane formed from a plurality of hydrophilic hollow fibers within the housing; and Equipped with each of the plurality of hollow fibers has an inner surface and an outer surface; the inner surfaces of the plurality of hydrophilic hollow fibers are arranged coaxially with respect to the array of the first ports, and the outer surfaces of the plurality of hollow fibers are arranged perpendicular to the array of the second ports; When used, Dialysate from a subject enters the filter device through the first port and exits in an outflow direction via the second port; and regenerated dialysate from the sorbent system enters the filter device through the second port and exits in an inflow direction via the first port; Peritoneal dialysis filter device.

[0009] 2. The peritoneal dialysis filter device further comprises a post-filtration system, the post-filtration system comprising: a first fluid path; a second fluid path comprising a post-filtration sorbent compartment; a switch for selecting between the first fluid path and the second fluid path; wherein the first fluid path and the second fluid path are both fluidly connected to the first port of the housing via the switch, and the sorbent compartment comprises a post-filtration sorbent suitable for removing one or more of water-soluble uremic toxins, protein-bound uremic toxins, low molecular weight proteins, endotoxins, exotoxins, inflammatory mediators, and microorganisms. Item 1. A peritoneal dialysis filter device according to item 1.

[0010] 3. A peritoneal dialysis filter device, comprising: A housing, a first compartment having a first port and a second port; a second compartment having a third port, an inlet port, and an outlet port; a switching means or device fluidly connected to the first port and the third port; a headspace cavity fluidly connecting the first compartment to the second compartment; a housing comprising: a first hollow fiber membrane formed from a plurality of hydrophilic hollow fibers in the first compartment of the housing, each of the plurality of hollow fibers having an inner surface and an outer surface, the inner surfaces of the plurality of hydrophilic hollow fibers being arranged coaxially with respect to the arrangement of the first ports, and the outer surfaces of the plurality of hollow fibers being arranged perpendicular to the arrangement of the second ports; a second hollow fiber membrane formed from a plurality of hydrophobic hollow fibers in the second compartment of the housing, each of the plurality of hollow fibers having an inner surface and an outer surface, the inner surfaces of the plurality of hydrophobic hollow fibers being arranged coaxially with respect to the arrangement of the third ports, and the outer surfaces of the plurality of hollow fibers being arranged perpendicular to the arrangement of the inlet ports and / or the outlet ports; Equipped with During use, Dialysate from a subject enters the first compartment of the filter device through the first port and exits the first compartment of the filter device in an outflow direction through the second port; and regenerated dialysate from a sorbent system enters the first compartment of the filter device through the second port and passes through a headspace cavity to the second compartment, the plurality of hydrophobic hollow fibers degassing the regenerated dialysate before it exits through the third port, and the removed gas exits the system via the outlet port. Peritoneal dialysis filter device.

[0011] 4. The peritoneal dialysis filter device further comprises a post-filtration system, the post-filtration system comprising: (a) a fluid pathway disposed between the third port of the housing and the switching means or device, the fluid pathway comprising a post-filtration sorbent compartment, the post-filtration sorbent compartment comprising a sorbent suitable for removing one or more of water-soluble uremic toxins, protein-bound uremic toxins, low molecular weight proteins, endotoxins, exotoxins, inflammatory mediators, and microorganisms; and / or (b) a post-filtration sorbent disposed within the headspace cavity, the sorbent being suitable for removing one or more of water-soluble uremic toxins, protein-bound uremic toxins, low molecular weight proteins, endotoxins, exotoxins, inflammatory mediators, and microorganisms. Equipped with Item 3. A peritoneal dialysis filter device according to item 3.

[0012] 5. A peritoneal dialysis filter device, comprising: A housing, a first compartment having a first port and a second port; a second compartment having a third port, a fourth port, an inlet port, and an outlet port; a switching means or device fluidly connected to the first port and the third port; a housing comprising: a first hollow fiber membrane formed from a plurality of hydrophilic hollow fibers in the first compartment of the housing, each of the plurality of hollow fibers having an inner surface and an outer surface, the inner surfaces of the plurality of hydrophilic hollow fibers being arranged coaxially with respect to the arrangement of the first ports, and the outer surfaces of the plurality of hollow fibers being arranged perpendicular to the arrangement of the second ports; a second hollow fiber membrane formed from a plurality of hydrophobic hollow fibers in the second compartment of the housing, each of the plurality of hollow fibers having an inner surface and an outer surface, the inner surfaces of the plurality of hydrophobic hollow fibers being arranged coaxially with respect to the arrangement of the third port and the fourth port, and the outer surfaces of the plurality of hollow fibers being arranged perpendicular to the arrangement of the inlet port and / or the outlet port; A peritoneal dialysis filter device comprising:

[0013] 6. The peritoneal dialysis filter device further comprises a post-filtration system, the post-filtration system comprising: (a) a fluid pathway disposed between the third port of the housing and the switching means or device, the fluid pathway comprising a post-filtration sorbent compartment, the post-filtration sorbent compartment comprising a sorbent suitable for removing one or more of water-soluble uremic toxins, protein-bound uremic toxins, low molecular weight proteins, endotoxins, exotoxins, inflammatory mediators, and microorganisms; and / or (b) further comprising a post-filtration sorbent disposed within the headspace cavity, the sorbent being suitable for removing one or more of water-soluble uremic toxins, protein-bound uremic toxins, low molecular weight proteins, endotoxins, exotoxins, inflammatory mediators, and microorganisms; Item 6. The peritoneal dialysis filter device according to item 5.

[0014] 7. A peritoneal dialysis system, comprising: a filter device; Adsorbent device and Equipped with the filter device is configured to receive and filter entire dialysate from a subject and, when operating in an outflow direction, to supply the filtered dialysate to the sorbent device; the filter device is configured to receive at least a portion of the regenerated dialysate from the sorbent device when operating in an inflow direction. Peritoneal dialysis system.

[0015] 8. The filter device a housing having a first port and a second port; a hollow fiber membrane formed from a plurality of hydrophilic hollow fibers within the housing, each of the plurality of hollow fibers having an inner surface and an outer surface; Equipped with the inner surfaces of the plurality of hydrophilic hollow fibers are aligned coaxially with respect to the first port, and the outer surfaces of the plurality of hollow fibers are aligned perpendicularly with respect to the second port; When used, The dialysate from the subject enters the filter device through the first port and exits in an outflow direction via the second port; and regenerated dialysate from the sorbent device enters the filter device through the second port and exits in an inflow direction via the first port; Item 7. A peritoneal dialysis system according to item 7.

[0016] 9. The filter device further comprises a post-filtration system, a first fluid path; a second fluid path comprising a post-filtration compartment; a switch for selecting between the first fluid path and the second fluid path; wherein the first fluid path and the second fluid path are both fluidly connected to the first port of the housing via the switch, and the sorbent compartment comprises a post-filtration sorbent suitable for removing one or more of water-soluble uremic toxins, protein-bound uremic toxins, low molecular weight proteins, endotoxins, exotoxins, inflammatory mediators, and microorganisms. Item 9. The peritoneal dialysis system according to item 8.

[0017] 10. The filter device A housing, a first compartment having a first port and a second port; a second compartment having a third port, an inlet port, and an outlet port; a switching means or device fluidly connected to the first port and the third port; a headspace cavity fluidly connecting the first compartment to the second compartment; a housing comprising: a first hollow fiber membrane formed from a plurality of hydrophilic hollow fibers in the first compartment of the housing, each of the plurality of hollow fibers having an inner surface and an outer surface, the inner surfaces of the plurality of hydrophilic hollow fibers being arranged coaxially with respect to the arrangement of the first ports, and the outer surfaces of the plurality of hollow fibers being arranged perpendicular to the arrangement of the second ports; a second hollow fiber membrane formed from a plurality of hydrophobic hollow fibers in the second compartment of the housing, each of the plurality of hollow fibers having an inner surface and an outer surface, the inner surfaces of the plurality of hydrophobic hollow fibers being arranged coaxially with respect to the arrangement of the third ports, and the outer surfaces of the plurality of hollow fibers being arranged perpendicular to the arrangement of the inlet ports and / or the outlet ports; Equipped with During use, the dialysate from the subject enters the first compartment of the filter device through the first port and exits the first compartment of the filter device in an outflow direction via the second port; and regenerated dialysate from the sorbent device enters the first compartment of the filter device through the second port and passes through the headspace cavity to the second compartment, the plurality of hydrophobic hollow fibers degassing the regenerated dialysate before it exits through the third port, and the removed gas exits the system via the outlet port. Item 7. A peritoneal dialysis system according to item 7.

[0018] 11. The filter device further comprises a post-filtration system, the post-filtration system comprising: (a) a fluid pathway disposed between the third port of the housing and the switching means or device, the fluid pathway comprising a post-filtration sorbent compartment, the post-filtration sorbent compartment comprising a sorbent suitable for removing one or more of water-soluble uremic toxins, protein-bound uremic toxins, low molecular weight proteins, endotoxins, exotoxins, inflammatory mediators, and microorganisms; and / or (b) further comprising a post-filtration sorbent disposed within the headspace cavity, the sorbent being suitable for removing one or more of water-soluble uremic toxins, protein-bound uremic toxins, low molecular weight proteins, endotoxins, exotoxins, inflammatory mediators, and microorganisms; Item 11. A peritoneal dialysis system according to item 10.

[0019] 12. The system further comprises a bypass means or bypass device, the bypass means or bypass device comprising: (a) a bypass fluid pathway connected to the sorbent device and configured to return regenerated dialysate to the subject without passing through any portion of the filter device; a switching means or device for selecting between sending regenerated dialysate to the filter device or to the bypass fluid path; or (b) a bypass fluid pathway connected to the sorbent device and configured to return regenerated dialysate to the subject through the second compartment of the filter device, the bypass fluid pathway including a fourth port, wherein the dialysate enters the second compartment through the fourth port and exits through the third port; a switching means or device for selecting between delivering regenerated dialysate to the second port or the fourth port of the filter device; Equipped with Item 12. The peritoneal dialysis system according to Item 10 or 11.

[0020] 13. The filter device A housing, a first compartment having a first port and a second port; a second compartment having a third port, a fourth port, an inlet port, and an outlet port; a switching means or device fluidly connected to the first port and the third port; a housing comprising: a first hollow fiber membrane formed from a plurality of hydrophilic hollow fibers in the first compartment of the housing, each of the plurality of hollow fibers having an inner surface and an outer surface, the inner surfaces of the plurality of hydrophilic hollow fibers being arranged coaxially with respect to the arrangement of the first ports, and the outer surfaces of the plurality of hollow fibers being arranged perpendicular to the arrangement of the second ports; a second hollow fiber membrane formed from a plurality of hydrophobic hollow fibers in the second compartment of the housing, each of the plurality of hollow fibers having an inner surface and an outer surface, the inner surfaces of the plurality of hydrophobic hollow fibers being arranged coaxially with respect to the arrangement of the third port and the fourth port, and the outer surfaces of the plurality of hollow fibers being arranged perpendicular to the arrangement of the inlet port and / or the outlet port; Equipped with Item 7. A peritoneal dialysis system according to item 7.

[0021] 14. The filter device further comprises a post-filtration system, (a) a fluid pathway disposed between the third port of the housing and the switching means or device, the fluid pathway comprising a post-filtration sorbent compartment, the post-filtration sorbent compartment comprising a sorbent suitable for removing one or more of water-soluble uremic toxins, protein-bound uremic toxins, low molecular weight proteins, endotoxins, exotoxins, inflammatory mediators, and microorganisms; and / or (b) further comprising a post-filtration sorbent disposed within the headspace cavity, the sorbent being suitable for removing one or more of water-soluble uremic toxins, protein-bound uremic toxins, low molecular weight proteins, endotoxins, exotoxins, inflammatory mediators, and microorganisms; Item 14. The peritoneal dialysis system according to Item 13.

[0022] 15. The system further comprises a bypass means or bypass device, the bypass means or bypass device comprising: (a) a bypass fluid pathway connected to the sorbent device and configured to return regenerated dialysate to the subject without passing through any portion of the filter device; a switching means or device for selecting between delivery of regenerated dialysate to the filter device or to the bypass fluid path; or (b) a bypass fluid pathway connected to the sorbent device and configured to return regenerated dialysate through the second compartment of the filter device to the subject, the dialysate entering the second compartment through the fourth port and exiting through the third port; a switching means or device for selecting between delivering regenerated dialysate to the second port or the fourth port of the filter device; Equipped with Item 15. The peritoneal dialysis system according to Item 13 or Item 14.

[0023] 16. The system further comprises a bypass means or bypass device, the bypass means or bypass device comprising: a bypass fluid pathway connected to the sorbent device and configured to return regenerated dialysate to the subject without passing through the filter device; a switching means or device for selecting between sending regenerated dialysate to the filter device or to the bypass fluid path; Equipped with Item 16. A peritoneal dialysis system according to any one of items 7 to 9, 10 to 12, and 13 to 15.

[0024] 17. A peritoneal dialysis method using the peritoneal dialysis system according to any one of items 7 to 16, comprising: (a) connecting a subject to the peritoneal dialysis system according to any one of items 7 to 16; (b) in the outflow direction, the dialysate is drawn from the subject's peritoneum and passes through the filter device before flowing to the sorbent device to provide regenerated dialysate; In the inflow direction, the regenerated dialysate is returned to the subject's peritoneum; At least a portion of the regenerated dialysate passes through a plurality of hydrophilic threads of the filter device. operating the system so that A method comprising:

[0025] 18. The peritoneal dialysis system is the peritoneal dialysis system according to item 10, wherein a first portion of the regenerated dialysate passes through the plurality of hydrophilic threads of the filter device, and a second portion of the regenerated dialysate passes through a bypass means or a bypass device in an inflow direction. Item 18. The method according to item 17.

[0026] 19. The peritoneal dialysis system according to item 16, wherein a first portion of the regenerated dialysate passes through the plurality of hydrophilic threads of the filter device, and a second portion of the regenerated dialysate passes through a bypass means or a bypass device in an inflow direction. Item 18. The method according to item 17.

[0027] 20. A hemodialysis machine, comprising: A housing, an exchange compartment having a blood inlet port, a dialysate inlet port, and a dialysate outlet port; a blood degassing compartment having a blood outlet port, a degassing gas inlet port, and a negative pressure / gas outlet port; a headspace cavity portion fluidly connecting the exchange compartment to the blood degassing compartment; a housing comprising: a first hollow fiber membrane formed from a plurality of hydrophilic hollow fibers in the exchange compartment of the housing, each of the plurality of hollow fibers having an inner surface and an outer surface, the inner surfaces of the plurality of hydrophilic hollow fibers being arranged coaxially with respect to the arrangement of the blood inlet ports, and the outer surfaces of the plurality of hollow fibers being arranged perpendicular to the arrangement of the dialysate inlet port and the outlet port; a second hollow fiber membrane formed from a plurality of hydrophobic hollow fibers in the blood degassing compartment of the housing, each of the plurality of hollow fibers having an inner surface and an outer surface, the inner surfaces of the plurality of hydrophobic hollow fibers being arranged coaxially with respect to the array of the blood outlet ports, and the outer surfaces of the plurality of hollow fibers being arranged perpendicular to the array of the gas inlet ports and / or negative pressure ports; Equipped with Hemodialysis machine.

[0028] 21. A hemodialysis machine, comprising: A housing, an exchange compartment having a blood inlet port, a blood outlet port, and a dialysate outlet port; a dialysate degassing compartment having a dialysate inlet port, a degassing gas inlet port, and a negative pressure / gas outlet port; a wall defining a fluid-impermeable boundary between the exchange compartment and the dialysate degassing compartment; a dialysate fluid portal that allows dialysate to move from the dialysate degassing compartment to the exchange compartment; a housing comprising: a first hollow fiber membrane formed from a plurality of hydrophilic hollow fibers in the exchange compartment of the housing, each of the plurality of hollow fibers having an inner surface and an outer surface, the inner surfaces of the plurality of hydrophilic hollow fibers being arranged coaxially with respect to the arrangement of the blood inlet port and the outlet port, and the outer surfaces of the plurality of hollow fibers being arranged perpendicular to the arrangement of the dialysate outlet ports; a second hollow fiber membrane formed from a plurality of hydrophobic hollow fibers in the dialysate degassing compartment of the housing, each of the plurality of hollow fibers having an inner surface and an outer surface, the inner surfaces of the plurality of hydrophobic hollow fibers being arranged coaxially with respect to the arrangement of the degassing gas inlet port and / or the negative pressure / gas outlet port, and the outer surfaces of the plurality of hollow fibers being arranged perpendicular to the arrangement of the dialysate inlet port and / or the dialysate fluid portal; Equipped with Hemodialysis machine.

[0029] 22. (a) the dialysate fluid portal is disposed within the wall; and / or (b) the apparatus further comprises a device for regenerating the dialysate; Item 22. The device according to item 21.

[0030] 23. A hemodialysis machine, comprising: A housing, an exchange compartment having a blood inlet port, a blood outlet port, a first dialysate inlet port, and a first dialysate outlet port; a dialysate degassing compartment having a second dialysate inlet port, a second dialysate outlet port, a degassing gas inlet port, and a negative pressure / gas outlet port; a wall defining a fluid-impermeable boundary between the exchange compartment and the dialysate degassing compartment; a housing comprising: a first hollow fiber membrane formed from a plurality of hydrophilic hollow fibers in the exchange compartment of the housing, each of the plurality of hollow fibers having an inner surface and an outer surface, the inner surfaces of the plurality of hydrophilic hollow fibers being arranged coaxially with respect to the arrangement of the blood inlet port and the outlet port, and the outer surfaces of the plurality of hollow fibers being arranged perpendicular to the arrangement of the first dialysate inlet port and the first dialysate outlet port; a second hollow fiber membrane formed from a plurality of hydrophobic hollow fibers in the dialysate degassing compartment of the housing, each of the plurality of hollow fibers having an inner surface and an outer surface, the inner surfaces of the plurality of hollow fibers being arranged coaxially with respect to the arrangement of the second dialysate inlet port and the second dialysate outlet port, and the outer surfaces of the plurality of hollow fibers being arranged perpendicular to the arrangement of the degassing gas inlet port and / or the negative pressure / gas outlet port; and optionally, the device further comprising a device for regenerating dialysate. Hemodialysis machine.

[0031] 24. A hemodialysis method, comprising a step of treating a subject in need thereof with the hemodialysis device according to any one of items 20 to 23. Hemodialysis methods.

[0032] 25. A method of controlling dialysate flow in a peritoneal dialysis system, the method comprising: determining a number of outflow and / or inflow parameters of dialysate from the subject flowing between the filter device and the sorbent device over one or more cycles, each cycle having an outflow phase and an inflow phase; comparing the parameter against a set of predefined conditions for controlling the flow of the dialysate through the filter device comprising a plurality of hydrophilic threads; allocating regenerated dialysate to flow from the sorbent device to the filter device during the inflow phase based on the comparison of the parameters; controlling a switching means or device to deliver an allocated amount of the regenerated dialysate to the plurality of hydrophilic threads of the filter device; Equipped with method.

[0033] 26. The parameters comprise an outflow rate of dialysate passing through the filter device during an outflow phase of the current cycle, and an allocated regenerated dialysate is delivered to the filter device during an inflow phase of the current cycle; Item 26. The method according to item 25.

[0034] 27. The parameters further comprise the outflow and / or inflow rates of the dialysate passing through the filter device during the outflow and / or inflow phases, respectively, of the preceding cycle. Item 27. The method according to item 26.

[0035] 28. The parameters comprise outflow volumes during outflow phases of the previous cycle and the current cycle, and the predefined condition is associated with a difference between the outflow volumes; Item 28. The method according to item 27.

[0036] 29. The parameters comprise an inflow volume of the dialysate passing through the filter device during an inflow phase of a current cycle and a previous cycle, the predefined condition being associated with a difference between the inflow volumes, and the allocated regenerated dialysate being delivered to the filter device during an inflow phase of a next cycle; Item 26. The method according to item 25.

[0037] 30. The regenerated dialysate of one of the one or more cycles is additionally allocated based on the allocated regenerated dialysate of one or more preceding cycles; Item 30. The method according to any one of Items 25 to 29.

[0038] 31. A kit of parts, comprising: (a) the peritoneal dialysis filter device according to claim 1; (b) Post-filtration system and wherein the post-filtration system comprises: a first fluid path; a second fluid path comprising a post-filtration sorbent compartment; a switch for selecting between the first and second fluid paths; the first fluid path and the second fluid path are both fluidly connected to the first port of the housing via the switch, and the sorbent compartment comprises a post-filtration sorbent suitable for removing one or more of water-soluble uremic toxins, protein-bound uremic toxins, low molecular weight proteins, endotoxins, exotoxins, inflammatory mediators, and microorganisms; Kit of parts.

[0039] 32. A kit of parts, comprising: (i) A peritoneal dialysis filter device according to item 3; (ii) a post-filtration system; wherein the post-filtration system comprises: (a) a fluid pathway disposed between the third port of the housing and the switching means or device, the fluid pathway comprising a post-filtration sorbent compartment, the post-filtration sorbent compartment comprising a sorbent suitable for removing one or more of water-soluble uremic toxins, protein-bound uremic toxins, low molecular weight proteins, endotoxins, exotoxins, inflammatory mediators, and microorganisms; and / or (b) a post-filtration sorbent disposed within the headspace cavity, the sorbent being suitable for removing one or more of water-soluble uremic toxins, protein-bound uremic toxins, low molecular weight proteins, endotoxins, exotoxins, inflammatory mediators, and microorganisms. Equipped with Kit of parts.

[0040] 33. A kit of parts, comprising: (i) A peritoneal dialysis filter device according to item 5; (ii) a post-filtration system; wherein the post-filtration system comprises: (a) a fluid pathway disposed between the third port of the housing and the switching means or device, the fluid pathway comprising a post-filtration sorbent compartment, the post-filtration sorbent compartment comprising a sorbent suitable for removing one or more of water-soluble uremic toxins, protein-bound uremic toxins, low molecular weight proteins, endotoxins, exotoxins, inflammatory mediators, and microorganisms; and / or (b) further comprising a post-filtration sorbent disposed within the headspace cavity, the sorbent being suitable for removing one or more of water-soluble uremic toxins, protein-bound uremic toxins, low molecular weight proteins, endotoxins, exotoxins, inflammatory mediators, and microorganisms; Kit of parts. [Brief explanation of the drawings]

[0041] [Figure 1] A sorbent-based dialysis system 100 incorporating an advanced filter system 110 of the present invention is depicted in three different phases: (a) outflow; (b) inflow washback; and (c) inflow bypass. [Figure 2]1 depicts a filter system incorporating a single chamber filter device 200 of the present invention in three different phases: (a) outflow; (b) inflow washback; and (c) inflow bypass. [Figure 3] 1 depicts a filter system incorporating a single chamber filter apparatus 200 of the present invention with an activated carbon purification module and additional switches in three different phases: (a) outflow; (b) inflow washback; and (c) inflow bypass. [Figure 4] 1 depicts a filter system incorporating a double chamber filter apparatus 300 of the present invention in three different phases: (a) outflow; (b) inflow washback; and (c) inflow bypass. [Figure 5] A filter system incorporating a double chamber filter device 302 of the present invention with activated carbon 331 disposed within headspace cavity portion 330 is depicted in three different phases: (a) outflow; (b) inflow washback; and (c) inflow bypass. [Figure 6] 1 depicts a filter system incorporating a dual chamber filter apparatus 300 of the present invention with an activated carbon compartment 380 in three different phases: (a) outflow; (b) inflow washback; and (c) inflow bypass. [Figure 7] 1 depicts a filter system incorporating a dual chamber filter apparatus 400 of the present invention with a bypass fluid path and a three-way switch 460 in three different phases: (a) outflow; (b) inflow washback; and (c) inflow bypass. [Figure 8] 1 depicts a peritoneal dialysis device 2000 according to U.S. Patent Application Publication No. 2018 / 0147338 that may be used with the filter device of the present invention. [Figure 9] 2 illustrates the integration of a single chamber filter device 200 of the present invention into an embodiment of a peritoneal dialysis machine 2000 in outflow mode. [Figure 10]2 illustrates the integration of a single chamber filter device 200 of the present invention into a peritoneal dialysis machine 2000 in inflow washback mode. [Figure 11] 2 illustrates the integration of a single chamber filter device 200 of the present invention into a peritoneal dialysis machine 2000 in inflow bypass mode. [Figure 12] 1 shows the configurations (a and b) of hemodialysis devices 1000 and 1500 of the present invention, respectively. [Figure 13] 1A and 1B depict an embodiment of an integrated sorbent-based continuous renal replacement therapy (CRRT) hemodialysis device 1000 in (a) outline view; and (b) top view. [Figure 14] 1 illustrates the integration of the hemodialysis machine 1000 into a hemodialysis system with other components. [Figure 15] 15A and 15B show an embodiment of a hemodialysis device 1501 for integrated sorbent-based hemodialysis with degassing of the dialysate in (a) an outline view; and (b) a top view. [Figure 16] 15 shows the integration of a hemodialysis machine 1501 into a hemodialysis system with other components. [Figure 17] Three-way manifold 460 for forming a three-way flow pattern as depicted in FIG. 7: (a) interconnected manifolds 460a and 460b; (b-d) depicting the positions of 460a and 460b in outflow, inflow washback, and inflow bypass modes, respectively. [Figure 18] 2 illustrates the integration of a dual chamber filter device 300 of the present invention into an embodiment of a peritoneal dialysis machine 2000 in outflow mode. [Figure 19] 1 illustrates the integration of a dual chamber filter device 300 of the present invention into a peritoneal dialysis machine 2000 in inflow washback mode. [Figure 20] 1 illustrates the integration of a dual chamber filter device 300 of the present invention into a peritoneal dialysis machine 2000 in inflow bypass mode. DETAILED DESCRIPTION OF THE INVENTION

[0042] The present invention seeks to solve some or all of the above identified problems through the use of filters as described in more detail herein below.

[0043] In a sorbent-based dialysis system 100, the flow schematic and major modules within the device can be shown as follows (FIG. 1). The entire treatment comprises several cycles of tidal dialysis. Each cycle begins with an outflow phase (FIG. 1a), during which fluid flows out of the patient 190, passes through the advanced filtering system 110, and then through the sorbent device 120 for detoxification and electrolyte control. The dialysate fluid accumulates in the reservoir chamber 130. After this outflow phase is completed, the inflow phase begins immediately and consists of two phases (FIGS. 1b and 1c). The first phase is the washback inflow (FIG. 1b), in which a portion of the regenerated dialysate is directed from the reservoir chamber 130 and through the advanced filtering system 110. In the second phase, the remaining regenerated dialysate (the majority) flows back from the reservoir chamber 130 directly into the patient's peritoneal membrane 190 (FIG. 1c) without passing through the advanced filtering system 110 (i.e., bypass inflow). The washback phase is necessary because proteins become trapped within the advanced filtering system 110 (e.g., within the walls of the hollow fibers, as described in more detail below) over the course of the outflow phase.

[0044] A level sensor may be implemented to monitor how long it takes for fluid to accumulate inside the reservoir or to leave the reservoir, or a volumetric flow sensor may serve the same purpose. This method may monitor the flow rate inside the system for that particular cycle, for both the outflow and inflow phases.

[0045] The peritoneal dialysis system according to the present invention comprises: filtering devices, Adsorbent Device and the filter device is configured to receive and filter total dialysate from the subject and, when operated in an outflow direction, to supply filtered dialysate to the sorbent device; The filter device may be configured to receive at least a portion of the regenerated dialysate from the sorbent device, and configured to pass at least a portion of the regenerated dialysate through the hydrophilic threads of the filter device and flow back into the subject when operated in the inflow direction.

[0046] In embodiments herein, the term "comprising" may be interpreted as requiring the recited features, but not limiting the presence of other features. Alternatively, the term "comprising" may relate to a situation where only the recited components / features are intended to be present (e.g., the term "comprising" may be replaced with the phrase "consists of" or "consists essentially of"). It is expressly contemplated that broader and narrower interpretations may apply to all aspects and embodiments of the present invention. That is, the term "comprising" and its equivalents may be replaced with the phrase "consists of" or the phrase "consists essentially of" or their equivalents, and vice versa.

[0047] As used herein, the term "sorbent device" may refer to any suitable device that can be used in combination with any filter device as described herein. This may be a purpose-built sorbent device, but it may also refer to a retrofit sorbent device configured to accommodate a filter device as disclosed herein. As will be understood, the sorbent devices described herein require the presence of the sorbent device 120 and reservoir chamber 130 described above, along with suitable pumping means or devices (e.g., gear pumps, membrane pumps, piston pumps, hydraulic pumps, pneumatic pumps, peristaltic pumps, and mechanical pumps).

[0048] The first filter system disclosed herein that may be used in a peritoneal dialysis system is a dead-end filter that may be used with any suitable peritoneal dialysis sorbent. Figures 2a-c show such a filter system in a peritoneal dialysis machine. This filter system is intended to prevent proteins and leukocytes from contacting the sorbent during effluent. Thus, disclosed herein is a peritoneal dialysis filter device 200 that: a housing 210 having a first port 220 and a second port 230; and a hollow fiber membrane 240 formed from a plurality of hydrophilic hollow fibers within the housing 210, each of the plurality of fibers having an inner surface and an outer surface; Equipped with The inner surfaces of the plurality of hydrophilic hollow fibers are arranged coaxially with respect to the array of the first ports 220, and the outer surfaces of the plurality of hollow fibers are arranged perpendicular to the array of the second ports 230, and in use: Dialysate from a subject enters the filter device 200 through the first port 220 and exits in an outflow direction via the second port 230; Regenerated dialysate from the sorbent device enters the filter device 200 through the second port 230 and exits in an inflow direction via the first port 220 .

[0049] The ports described herein may be solely open or may be adjustable between open and closed settings, thereby exerting further control over fluid flow.

[0050] Although the system may operate without it, the embodiments described below also utilize a bypass means or device. a bypass fluid pathway connected to the sorbent device and configured to return the regenerated dialysate to the subject without passing through the filter device; and A switching means or device for selecting whether the regenerated dialysate is sent to the filter device or to the bypass fluid path. It may comprise:

[0051] "Switching means or switching device" may refer to any suitable device that can open or close a fluid communication means or shunt fluid between one or more fluid communication lines. Examples of suitable switching means and switching devices that may be referred to herein include, but are not limited to, valves (e.g., ball valves, switch valves, etc.), stopcocks, and combinations of T-junctions and switches. If the system does not include a bypass means or device, the entire regenerated dialysate may pass through the filter device.

[0052] The dead-end filter 200 may be used in a minimum two-port configuration (i.e., a first port (220) and a second port (230)), but it may also be provided in a three- or four-port configuration (a third port 245 and a fourth port 250) and may be used to improve priming of the entire device at the start of treatment. During the inflow phase, flow may be directed back into the filter to wash back proteins and white blood cells to the patient. This may reduce the protein loss common in conventional peritoneal dialysis. This concept is not limited by a particular filter shape, which may be round, square, spiral, sheet, etc.

[0053] During operation, the first step is the outflow phase (FIG. 2a), which may last any suitable amount of time (e.g., 5 minutes) and involve the removal of fluid (e.g., 250 mL) from the subject. In this first step, the first port (220) and the second port (230) are set to open (if they can be opened or closed), and spent dialysate is drawn from the patient's peritoneum 9 through the first port 220 of the filter device 200, thereby flowing onto the inner surface of the hollow fiber membrane (because the first port is aligned coaxially with the hollow fibers), where it flows into the internal flow passages of the hydrophilic hollow fibers 240. Negative pressure applied to the outer surface of the hollow fibers transports water and low molecular weight solutes (e.g., <40 kDa; as will be appreciated, the molecular weight cutoff depends on the pore size of the filter, which can be varied to any suitable value by one skilled in the art) from the internal flow path of hollow fibers 240 through the porous wall matrix to external chamber 260 surrounding the exterior of the hollow fibers. As will be appreciated, positive pressure can instead be used to achieve the same effect. Larger solutes, such as proteins and fibrin, are trapped on the luminal surface of hollow fibers 240, preventing their interaction with the internal components of purification system 270. The filtered spent dialysate is then drawn from second port 230 of filter device 200 by pump 275 to purification system 270 via switch 279. The filtered spent dialysate is then processed by purification system 270 into regenerated fresh dialysate.

[0054] Although 40 kDa is used above as the molecular weight cutoff of the filter, it will be understood that any suitable pore size of the filter may be used. For example, a suitable pore size of the filter that may be used in all of the embodiments disclosed herein may be a pore size that results in a molecular weight cutoff in the range of 5 to 7 kDa.

[0055] As used herein, the term "coaxially arranged" is intended to mean that the axis of the first port is aligned with the directional axis of the lumen of the hollow fiber.

[0056] The regenerated fresh dialysate is then returned to the subject's peritoneum by two means. In the first case (FIG. 2b), the first port (220) and the second port (230) are held in an open setting (if they can be closed), and the regenerated fresh dialysate is transported from the purification system 270 by pump 275 to the second filter port 230 via switch 279. Downstream of the purification system 270, the fresh dialysate encounters and mixes with the spent dialysate from the preceding outflow. The mixture of fresh dialysate and spent dialysate (the combination of which constitutes the washback fluid) flows into the filter chamber 260 and exerts a positive fluid pressure against the exterior surfaces of the hollow fibers 240. This positive fluid pressure forces water and low molecular weight solutes, such as glucose and electrolytes, through the porous wall matrix and through the interior flow channels of the hydrophilic fibers 240. During this process, any proteins or biomaterials trapped on the fiber lumen are removed, defouling the inner pores of the fiber and restoring the original filter surface area. Without being bound by theory, it is believed that washback is more effective when it occurs across the fiber rather than through it. When washback occurs through the fiber, resistance to fluid movement is virtually nonexistent. The washback fluid exits the filter through port 220 and re-enters the peritoneum 9. The volume of the washback fluid is optimized to ensure that the filter remains patent during the next outflow cycle while minimal spent fluid is returned to the patient. As can be seen, only a small amount of regenerated dialysate is required for washback under normal circumstances. Thus, the amount of fluid used is relatively small (e.g., 50 mL), and the time required to complete the washback phase can be less than one minute.

[0057] As shown in FIG. 2c, the remaining regenerated fresh dialysate does not pass through filter device 200 but instead is transported from purification system 270 by pump 275 to bypass line 280 via switch 279. In this situation, first port (220) and second port (230) may be set to closed (if they have this setting). As will be appreciated, switch 279 may prevent fluid from flowing to filter device 200 without requiring the ports to be switched from an open to a closed setting. Downstream of purification system 270, the fresh dialysate encounters and mixes with a small amount of washback fluid from the preceding inflow washback cycle. Due to the routing by switch 279, the majority of the fresh dialysate bypasses chamber 260 and instead re-enters peritoneum 9 directly via bypass line 280. The volume of the inflow bypass fluid is optimized to return maximum fresh fluid to the patient to maintain a sufficient dialysate / serum gradient for efficient toxin removal and electrolyte control. For example, the inlet bypass fluid may be 200 mL (compared to 250 mL for the outlet). More generally, Outflow: The device draws "T" liters of fluid from the patient and detoxifies it; Inflow: The device returns "T" liters of "detoxified" fluid to the patient, Washback: x% of fluid is pushed back into the patient, Bypass: 1-x% of the fluid is bypassed through the advanced filter and pushed directly back to the patient.

[0058] The system may be supplemented by a post-filtration system. Thus, the filter device may further comprise a post-filtration system, which includes: a first fluid path; a second fluid path comprising a post-filtration sorbent compartment; and The device includes a switch for selecting between the first fluid path and the second fluid path, both of which are fluidly connected to the first port of the housing via the switch, and the adsorbent compartment is suitable for removing one or more of water-soluble uremic toxins, protein-bound uremic toxins, low molecular weight proteins, endotoxins, exotoxins, inflammatory mediators, and microorganisms.

[0059] This configuration will now be described with reference to Figures 3a-3c. The only difference between this design and the first is the inclusion of an activated carbon purification module and switch, along with the appropriate fluid paths. It will be understood that the activated carbon purification compartment is an embodiment of the post-filtration sorbent compartment described above. Examples of other suitable materials for use in the post-filtration sorbent compartment are described below. For the avoidance of doubt, activated carbon may be used as an example in further embodiments below, but this is not intended to limit the design to activated carbon; i.e., any other suitable material that can be used in a post-filtration system to achieve the goals described below may be used instead.

[0060] The outflow operation (FIG. 3a) is substantially the same as that described above, except for the addition of a switch 225 configured to be in fluid communication with the first port 220 during outflow operation of the device. The main difference is when the device is operated in the inflow direction.

[0061] Thus, in the first step of the inflow operation (FIG. 3b), regenerated fresh dialysate is returned to the subject's peritoneal membrane 9 by two means. In the first case, the regenerated fresh dialysate is transported from the purification system 270 by pump 275 to the second filter port 230 via switch 279. Downstream of the purification system 270, the fresh dialysate encounters and mixes with the spent dialysate from the preceding outflow. The mixture of fresh and spent dialysate (the combination of which constitutes the washback fluid) enters the filter chamber 260 and exerts a positive fluid pressure against the exterior surfaces of the hollow fibers 240. This positive fluid pressure forces low-molecular-weight solutes, such as water, glucose, and electrolytes, through the porous wall matrix and through the internal flow paths of the hydrophilic fibers 240. During this process, any proteins or biological material trapped on the fiber lumen is removed, defouling the inner pores of the fibers and restoring the original filter surface area. Without being bound by theory, it is believed that washback is more effective when it occurs across the thread rather than through it. When washback occurs through the thread, resistance to fluid movement is virtually nonexistent. The washback fluid exits the filter through port 220 and is routed through the compartment 290 via switch 225, where PBUT and water-soluble uremic toxins are removed, for example, with activated charcoal. The treated washback fluid re-enters the peritoneum 9. The volume of the washback fluid is optimized to ensure that filter patency is maintained during the next flush cycle while minimal spent fluid is returned to the patient.

[0062] As shown in FIG. 3c, regenerated fresh dialysate is transported from purification system 270 by pump 275 through switch 279 to bypass line 280. Downstream of purification system 270, the fresh dialysate encounters and mixes with a small amount of washback fluid from the preceding inflow washback cycle. Routing by switch 279 causes the mostly fresh dialysate to bypass chamber 260 and instead enter bypass line 280. The mostly fresh dialysate is then routed through compartment 290 via switch 225, where PBUT and water-soluble uremic toxins are removed, for example, with activated charcoal. The mostly fresh dialysate re-enters peritoneal membrane 9. As previously mentioned, the volume of the inflow bypass fluid is optimized to return maximum fresh fluid to the patient to maintain a sufficient dialysate / serum gradient for efficient toxin removal and electrolyte control.

[0063] In an alternative configuration, a second type of filter device may be used. This filter system 300 is somewhat more complex and A housing, a first compartment 311 having a first port 312 and a second port 313; a second compartment 315 having a third port 316, an inlet port 317, and an outlet port 318; a switching means or device 320 fluidly connected to the first port 312 and the third port 316; and a headspace cavity portion 330 fluidly connecting the first compartment 311 to the second compartment 315; a housing 310 comprising: a first hollow fiber membrane (340) formed from a plurality of hydrophilic hollow fibers in the first compartment (311) of the housing (310), each of the plurality of hollow fibers having an inner surface and an outer surface, the inner surfaces of the plurality of hydrophilic hollow fibers being arranged coaxially with respect to the arrangement of the first ports (312), and the outer surfaces of the plurality of hollow fibers being arranged perpendicular to the arrangement of the second ports (313); a second hollow fiber membrane (350) formed from a plurality of hydrophobic hollow fibers in the second compartment (315) of the housing (310), each of the plurality of hollow fibers having an inner surface and an outer surface, the inner surfaces of the plurality of hydrophobic hollow fibers being arranged coaxially with respect to the arrangement of the third ports (316), and the outer surfaces of the plurality of hollow fibers being arranged perpendicular to the arrangement of the inlet (317) and / or outlet (318) ports; Equipped with During use, Dialysate from a subject enters the first compartment 311 of the filter device 300 through the first port 312 and exits the first compartment of the filter device in an outflow direction via the second port 313; and Regenerated dialysate from the sorbent device enters the first compartment 311 of the filter device through the second port 313 and passes through a headspace cavity 330 to the second compartment 315, the hydrophobic hollow fibers degas the regenerated dialysate before it exits through the third port, and the removed gas exits the system via the outlet port 318.

[0064] As used herein, the term "degas" or "degasses" is intended to refer to the removal of unwanted gases and / or bubbles from the regenerated dialysate, or, as the case may be, other fluids. An example of an unwanted gas that may be removed is carbon dioxide. As will be understood, not all of the unwanted gases may be removed from the regenerated dialysate by the above process, but at least a portion (e.g., 10-99.99%) of the gases may be removed. In certain embodiments, when attempting to remove unwanted gases such as carbon dioxide, a sweep gas (e.g., air, oxygen, a mixture of oxygen and nitrogen, or carbogen (95% oxygen and 5% CO)) may be used to replace the carbon dioxide in the regenerated dialysate. This sweep gas may be used alone or in combination with negative pressure. In alternative embodiments, negative pressure alone is applied, which may therefore act to remove some or all of the gases and bubbles in the regenerated dialysate. As will be understood, the exact sweep gas (and its flow rate) used may depend on the application and may be determined by one skilled in the art using their experience and knowledge. For example, if a subject has respiratory failure, one skilled in the art may choose to use the flow rate and sweep gas recommended in the Extracorporeal Life Support Organization (ELSO) Guidelines for Adult Respiratory Failure, August 2017.

[0065] As previously mentioned, the system may be operated using a bypass means or device, which will be described below. The bypass means or device may comprise: (a) a bypass fluid pathway connected to the sorbent device and configured to return regenerated dialysate to the subject without passing through any portion of the filter device; a switching means or device 360 ​​for selecting between sending the regenerated dialysate to the filter device or to the bypass fluid path; or (b) a bypass fluid pathway connected to the sorbent device and configured to return regenerated dialysate to the subject, the bypass fluid pathway passing through a second compartment of the filter device, the second compartment having a fourth port 319, such that the dialysate enters the second compartment 315 through the fourth port 319 and exits through the third port 316; and a switching means or device 360 ​​for selecting delivery of the regenerated dialysate to either the second port or the fourth port of the filter device. There are two possible configurations:

[0066] An embodiment of this configuration is disclosed in Figures 4a to 4c.

[0067] During the outflow phase ( FIG. 4 a), spent dialysate is withdrawn from the patient's peritoneum 9 through a first port 312 of the hollow fiber membrane (via switch 360). When the ports can be opened and closed, the first and second ports are in an open position, while the other ports are in a closed position. The spent dialysate then enters the internal flow path of the plurality of hydrophilic hollow fibers 340. Negative pressure applied to the outer surface of the plurality of hollow fibers transports water and low molecular weight solutes (e.g., <40 kDa) from the internal passage of the plurality of hollow fibers 340 through the porous wall matrix and into a first chamber 311 surrounding the exterior of the plurality of hollow fibers. Larger solutes, such as proteins and fibrin, are trapped on the luminal surfaces of the plurality of hollow fibers, preventing their interaction with the internal components of a purification system 375. The filtered spent dialysate is then withdrawn from a second port 313 of the hollow fiber membrane by a pump 370 via switch 320 to a purification system 375. The filtered spent dialysate is then processed by a purification system 375 into regenerated fresh dialysate.

[0068] During the first part of the inflow phase (FIG. 4b), regenerated fresh dialysate is transported from the purification system 375 by the pump 370 through the switch 320 to the second filter port 313. Downstream of the purification system 375, the fresh dialysate encounters and mixes with the spent dialysate from the preceding outflow. The mixture of fresh dialysate and spent dialysate (the combination of which constitutes the washback fluid) enters the first filter chamber 311 and exerts positive fluid pressure against the exterior surface of the hollow fibers 340. This positive fluid pressure forces water and low-molecular-weight solutes, such as glucose and electrolytes, through the porous wall matrix and through the internal flow channels of the hydrophilic fibers 340. During this process, any proteins or biomaterials trapped on the fiber lumen are removed, defouling the inner pores of the fibers and restoring the original filter surface area. The washback fluid is routed through the hollow fiber headspace 330 into the internal flow channels of the hollow fibers 350 contained within the second chamber 315. The washback fluid may be degassed through the use of sweep gas through port 317, or negative pressure may be applied through port 318, or a combination thereof may be used. The degassed washback fluid is removed through filter through port 316 and re-enters peritoneum 9 via switch 360. The volume of washback fluid is optimized to return minimal spent fluid to the patient while ensuring that the filter remains patent during the next flush cycle. When the ports can be opened or closed, the second, third, outlet, and fourth ports are in the open position, while the other ports are in the closed position.

[0069] The remaining regenerated fresh dialysate can bypass the first chamber, as shown in FIG. 4c. Ports can be opened or closed; the third, inlet, outlet, and fourth ports are in open positions, while the other ports are in closed positions. In this embodiment, the remaining regenerated fresh dialysate is transported from the purification system 375 by the pump 370 to the fourth filter port 319 via the switch 320. Due to routing by the switch 320, the fluid bypasses the first chamber 311 and instead enters the internal flow path of the hydrophobic yarn 350, which is surrounded by the second chamber 315. Downstream of the purification system 375, the fresh dialysate encounters and mixes with a small amount of washback fluid from the preceding inflow washback cycle. The mostly fresh dialysate enters the internal flow path of the hydrophobic yarn 350 and is degassed via the previously described mechanisms and ports (gas, negative pressure, or a combination of both via 317 / 318). Degassed, mostly fresh dialysate is infused through filter outlet port 316 and re-enters peritoneum 9 via switch 360. The volume of inlet bypass fluid is optimized to return maximum fresh fluid to the patient to maintain an adequate dialysate / serum gradient for efficient toxin removal and electrolyte control.

[0070] The system includes a post-filtration system, the post-filtration system comprising: (a) a fluid pathway disposed between the third port of the housing and the switching means or device, the fluid pathway comprising a post-filtration sorbent compartment, the post-filtration sorbent compartment comprising a sorbent suitable for removing one or more of water-soluble uremic toxins, protein-bound uremic toxins, low molecular weight proteins, endotoxins, exotoxins, inflammatory mediators, and microorganisms; and / or (b) The headspace cavity may further comprise a post-filtration sorbent disposed within the headspace cavity, the sorbent being suitable for removing one or more of water-soluble uremic toxins, protein-bound uremic toxins, low molecular weight proteins, endotoxins, exotoxins, inflammatory mediators, and microorganisms.

[0071] In all embodiments of the present invention, including certain types of post-filtration sorbent systems, the post-filtration sorbent may be any suitable sorbent capable of removing one or more of water-soluble uremic toxins, protein-bound uremic toxins, low-molecular-weight proteins, endotoxins, exotoxins, inflammatory mediators, and microorganisms. Suitable sorbents for this purpose include those disclosed in Ronco C, Dell'Aquila R, Rodighiero MP (eds): Peritoneal dialysis: A Clinical Update. Contrib Nephrol. Basel, Karger, 2006, vol. 150, pp. 336-343, incorporated herein by reference, particularly those disclosed in Table 1 of the above-mentioned publication. Specific examples of sorbents that may be mentioned herein include, but are not limited to, activated carbon and macroporous polymeric materials.

[0072] The latter embodiment (filter device 302) is disclosed in Figures 5a-5c. There are no differences in outflow behavior that can be understood from the above description of Figure 4a, and therefore will be omitted here for the sake of brevity.

[0073] In the first part of the inflow phase (FIG. 5 b ), fresh regenerated dialysate is transported from the purification system 375 by the pump 370 through the switch 320 to the second filter port 317 .

[0074] Downstream of the purification system 375, the fresh dialysate encounters and mixes with the spent dialysate from the preceding outflow. The mixture of fresh dialysate and spent dialysate (the combination of which constitutes the washback fluid) enters the first filter chamber 311 and exerts positive fluid pressure against the exterior surfaces of the hollow fibers 340. This positive fluid pressure forces water and low-molecular-weight solutes, such as glucose and electrolytes, through the porous wall matrix and through the internal flow channels of the hydrophilic fibers 340. During this process, any proteins or biomaterials trapped on the fiber lumen are removed, defouling the inner pores of the fibers and restoring the original filter surface area. The washback fluid is routed through the headspace compartment 330, where PBUT and water-soluble uremic toxins are removed by a sorbent 331, such as activated carbon, before the fluid enters the internal flow channels of the hydrophobic fibers 350 contained within the second chamber 315. The washback fluid may be degassed through the use of sweep gas through port 317, or negative pressure may be applied through port 318, or a combination thereof may be used. The degassed washback fluid is removed through filter through port 316 and re-enters the peritoneum 9 via switch 360. The volume of washback fluid is optimized to return minimal spent fluid to the patient while ensuring that the filter remains patent during the next flush cycle. When the ports can be opened and closed, the second port, third port, outlet port, and fourth port are in the open position, while the other ports are in the closed position.

[0075] The remaining regenerated fresh dialysate can bypass the first chamber, as shown in FIG. 5c. When the ports can be opened or closed, the third port, the inlet port, the outlet port, and the fourth port are in the open position, while the other ports are in the closed position. In this embodiment, the remaining regenerated fresh dialysate is transported from the purification system 375 by the pump 370 to the fourth filter port 319 via the switch 320. Due to the routing by the switch 320, the fluid bypasses the first chamber 311 and instead enters the internal flow path of the hydrophobic thread 350, which is surrounded by the second chamber 315. Downstream of the purification system 375, the fresh dialysate encounters and mixes with a small amount of washback fluid from the preceding inflow washback cycle. After passing through the filter port 319, the dialysate enters the headspace compartment 330, where PBUT and water-soluble uremic toxins are removed by an adsorbent, such as activated carbon. The dialysate then enters the internal flow path of the hydrophobic thread 350 enclosed within the second chamber 315 and can be degassed via the mechanisms and ports previously described (gas, negative pressure, or a combination of both via 317 / 318). The degassed, mostly fresh dialysate is infused through the filter outlet port 316 and re-enters the peritoneum 9 via switch 360. The volume of the inlet bypass fluid is optimized to return maximum fresh fluid to the patient to maintain a sufficient dialysate / serum gradient for efficient toxin removal and electrolyte control.

[0076] As mentioned above, the system may operate using a filter device that employs an external activated carbon compartment, as illustrated in Figures 6a-6c, and it will again be understood that this activated carbon compartment is equivalent to the external post-filtration sorbent compartment previously described.

[0077] The operation of Figure 6a is substantially identical to that described with reference to Figure 4a and is therefore omitted here for the sake of brevity.

[0078] During the first part of the inflow phase (FIG. 6b), regenerated fresh dialysate is transported from the purification system 375 via the switch 320 to the second filter port 313 by the pump 370. Downstream of the purification system 375, the fresh dialysate encounters and mixes with the spent dialysate from the preceding outflow. The mixture of fresh dialysate and spent dialysate (the combination of which constitutes the washback fluid) enters the first filter chamber 311 and exerts positive fluid pressure against the exterior surface of the hollow fibers 340. This positive fluid pressure forces water and low-molecular-weight solutes, such as glucose and electrolytes, through the porous wall matrix and through the internal flow channels of the hydrophilic fibers 340. During this process, any proteins or biomaterials trapped on the fiber lumen are removed, defouling the inner pores of the fibers and restoring the original filter surface area. The washback fluid is routed through the hollow fiber headspace 330 into the internal flow channels of the hydrophobic fibers 350 contained within the second chamber 315. The washback fluid may be degassed using sweep gas through port 317, or negative pressure may be applied through port 318, or a combination thereof. The degassed washback fluid exits filter through port 316 and is infused through compartment 380, where PBUT and water-soluble uremic toxins are removed with activated charcoal. The purified washback fluid re-enters peritoneum 9 via switch 360. The volume of washback fluid is optimized to return minimal spent fluid to the patient while ensuring filter patency is maintained during the next flush cycle. When the ports can be opened or closed, the second, third, outlet, and fourth ports are in the open position, while the other ports are in the closed position.

[0079] The remaining regenerated fresh dialysate can bypass the first chamber, as shown in FIG. 6c. When the ports can be opened or closed, the third port, the inlet port, the outlet port, and the fourth port are in the open position, while the other ports are in the closed position. In this embodiment, the remaining regenerated fresh dialysate is transported from the purification system 375 by the pump 370 to the fourth filter port 319 via the switch 320. Due to the routing by the switch 320, the fluid bypasses the first chamber 311 and instead enters the internal flow path of the hydrophobic yarn 350, which is surrounded by the second chamber 315. Downstream of the purification system 375, the fresh dialysate encounters and mixes with a small amount of washback fluid from the preceding inflow washback cycle. The mostly fresh dialysate flows into the internal flow path of the hydrophobic yarn 350 and is degassed via the previously described mechanisms and ports (gas, negative pressure, or a combination of both via 317 / 318).

[0080] Degassed, mostly fresh dialysate is infused through filter outlet port 316 and through compartment 380, where PBUT and water-soluble uremic toxins are removed by activated charcoal. The mostly fresh dialysate re-enters peritoneum 9 via switch 360. The volume of the inlet bypass fluid is optimized to maximize fresh fluid return to the patient to maintain a sufficient dialysate / serum gradient for efficient toxin removal and electrolyte control. The positioning of compartment 380 is advantageous because it allows for the simultaneous removal of PBUT from the washback fluid and uremic toxins from the returned dialysate, which would not be possible if activated charcoal were located in purification system 375.

[0081] For the filter device of the present invention to function optimally, the filter system must be primed to remove trapped air from the system. The priming process is set out below with reference to the configuration in Figures 6a-c. 1) A fill bag (instead of the peritoneal membrane 9) containing fresh dialysate is connected to switch 360. 2) Ports 316, 317, 318, and 319 are in a closed position while ports 312 and 313 are open. Switches 360 and 320 are routed such that the fill bag is in fluid communication with port 312 and port 313 is in fluid communication with pump 370. 3) The pump 370 is switched on to prime the hydrophilic filter 340 by filling the lumen of the thread, the outer chamber 311, and the outlet port 313 with dialysate. 4) Once priming of hydrophilic thread 340 is complete, pump 370 is switched off. Switch 360 is then routed to connect the fill bag to port 316, while switch 320 is routed to connect pump 370 to port 319. 5) Ports 317 and 318 are held in the closed position. 6) The pump 370 is switched on to prime the lumen of the hydrophobic thread 350. 7) Priming is complete and the fill bag is removed. The device can be connected to the patient for use. There may be some unprimed area in the headspace 330, but this is resolved in the subsequent inflow washback, which pushes the air in the headspace 330 out to the hydrophobic fibers 350 to be removed.

[0082] While the priming process allows the filter system to perform at its best, priming is optional and not absolutely necessary for the filter device (and therefore the dialysis system) to function. The above steps can be applied, by analogy, to priming any of the double-chamber filter devices disclosed herein. Additionally, steps 1-3 and 7 can also be used to prime the single-chamber filters described herein.

[0083] In an alternative configuration, a second type of filter device may be used. This filter system 400 is somewhat more complex and A housing 410, a first compartment 411 having a first port 412 and a second port 413; a second compartment 415 having a third port 416, a fourth port 419, an inlet port 417, and an outlet port 418; a switching means or device 460 fluidly connected to the first port 412 and the third port 416; a housing 410 comprising: a first hollow fiber membrane 440 formed from a plurality of hydrophilic hollow fibers in the first compartment 411 of the housing 410, each of the plurality of hollow fibers having an inner surface and an outer surface, the inner surfaces of the plurality of hydrophilic hollow fibers being arranged coaxially with respect to the arrangement of the first ports 412, and the outer surfaces of the plurality of hollow fibers being arranged perpendicular to the arrangement of the second ports 413; a second hollow fiber membrane 450 formed from a plurality of hydrophobic hollow fibers in the second compartment 415 of the housing 410, each of the plurality of hollow fibers having an inner surface and an outer surface, the inner surfaces of the plurality of hydrophobic hollow fibers being arranged coaxially with respect to the arrangement of the third port 416 and the fourth port 419, and the outer surfaces of the plurality of hollow fibers being arranged perpendicular to the arrangement of the inlet 417 and / or outlet 418 ports; Equipped with.

[0084] As mentioned above, the system may be operated using a bypass means or device, which is described below. The bypass means or device may comprise: (a) a bypass fluid pathway connected to the sorbent device and configured to return regenerated dialysate to the subject without passing through any portion of the filter device; a switching means or device 420 for selecting between sending the regenerated dialysate to the filter device or to the bypass fluid path; or (b) a bypass fluid pathway connected to the sorbent device and configured to return regenerated dialysate to the subject through a second compartment 415 of the filter device, the dialysate entering the second compartment 415 through a fourth port 419 and exiting through a third port 416; a switching means or device 420 for selecting between delivering the regenerated dialysate to the second port 413 or the fourth port 419 of the filter device; There are two possible configurations that may comprise:

[0085] An embodiment of this configuration is disclosed in Figures 7a to 7c.

[0086] The outflow operation of the device (Figure 7a) is substantially identical to that described for Figure 4a and therefore this will not be described again for the sake of brevity.

[0087] The first stage of the inflow mode is depicted in FIG. 7b, with all ports in the open position (if they can be opened or closed). Regenerated fresh dialysate is transported from the purification system 475 by the pump 470 to the second filter port 413 via the switch 420. Downstream of the purification system 475, the fresh dialysate encounters and mixes with the spent dialysate from the preceding outflow. The mixture of fresh dialysate and spent dialysate (the combination of which constitutes the washback fluid) enters the first filter chamber 411 and exerts a positive fluid pressure against the exterior surface of the hollow fibers 440. This positive fluid pressure forces low-molecular-weight solutes, such as water, glucose, and electrolytes, through the porous wall matrix and through the internal flow paths of the hydrophilic fibers 440. During this process, any proteins or biomaterials trapped on the fiber lumen are removed, defouling the inner pores of the fibers and restoring the original filter surface area. Washback fluid exits through port 412 and is directed to inlet port 416 of second chamber 415 via three-way switch 460. The fluid enters the internal flow path of the hydrophobic thread and may be degassed using sweep gas through port 417, or negative pressure may be applied through port 418, or a combination thereof may be used. The degassed washback fluid is removed through filter through port 419 and re-enters peritoneum 9 via switch 460. The washback fluid volume is optimized to ensure filter patency is maintained during the next flush cycle while minimal spent fluid is returned to the patient.

[0088] As shown in FIG. 7c, the remaining regenerated fresh dialysate is transported from the purification system 475 by pump 470 to the fourth filter port 419 via switch 420. Due to routing via switch 420, the fluid bypasses the first chamber 411 and instead enters the internal flow path of the hydrophobic yarn 450 enclosed within the second chamber 415. Downstream of the purification system 475, the fresh dialysate encounters and mixes with a small amount of washback fluid from the preceding inflow washback cycle. Mostly fresh dialysate enters the internal flow path of the hydrophobic yarn 450 and is degassed via the previously described mechanisms and ports (gas, negative pressure, or a combination of both via 417 / 418). The degassed mostly fresh dialysate is infused through the filter outlet port 416 and re-enters the peritoneum 9 via switch 460. The volume of the inflow bypass fluid is optimized to return maximum fresh fluid to the patient to maintain a sufficient dialysate / serum gradient for efficient toxin removal and electrolyte control. In this mode, ports 412 and 413 are blocked, while other ports are open (if they can be blocked).

[0089] As can be seen, the three-way switch 460 in Figures 7a-7c can be a manifold that connects to four different outlets / inlets, allowing multiple flow paths to be provided (as shown in Figures 17a-d). The manifold comprises two separate parts (460a and 460b) that can rotate relative to one another, and which combine to form a leak-tight fit (Figure 17a).

[0090] Manifold component 460b has three through-holes (463, 464, and 465) with sides (bottom of 460b) fluidly connected to outlet / inlet ports 419, 416, and 412, respectively, of device 400. Manifold component 460a includes one through-hole 461 with a side (top) in fluid communication with peritoneum 9, and one internal conduit 462 with openings that can be aligned with two of the corresponding holes (464 and 465) in component 460b to allow fluid communication between the multiple ports.

[0091] As will be appreciated, the direction of dialysate flow is controlled by the alignment of the through-holes (463, 464, and 465) in part 460b with the openings of internal conduit 462 and through-hole 461 in part 460a. One or both of manifold parts 460a and 460b may be rotated to facilitate alignment of the through-holes and openings of internal conduit 462. That is, one of the manifold parts may be fixed while the other is in operation, or both parts may be in operation.

[0092] In the outflow mode, parts 460a and 460b are in the position shown in Figure 17b, whereby through-holes 461 and 465 are aligned, which allows the flow of dialysate from the peritoneum 9 to the inlet port 412 of the device 400. However, through-holes 463 and 464 are not aligned with the conduit 462, which blocks the flow path between ports 419 and 416.

[0093] In the inflow washback mode (FIG. 17c), through-holes 461 and 463 are aligned, which allows the flow of dialysate from outlet port 419 to peritoneum 9. Additionally, through-holes 464 and 465 are aligned with conduit 462, which therefore allows the flow of dialysate from ports 412 to 416.

[0094] In the inflow bypass mode (FIG. 17d), through-holes 461 and 464 are aligned, thus allowing the flow of dialysate from outlet port 416 to peritoneum 9. However, through-holes 463 and 465 are not aligned with the opening of conduit 462, which blocks the flow path between ports 412 and 419.

[0095] It will be appreciated that the system may be configured to include a post-filtration system in the manner previously described.

[0096] As will be appreciated, the filter device described herein can be used with any suitable peritoneal dialysis system. This may be a system purpose-built to incorporate the device, or it may be a device configured to incorporate the device. As an example of this, we will now describe how to retrofit the filter device of U.S. Patent Application Publication No. 2018 / 0147338, which is incorporated herein by reference in its entirety. One embodiment of this dialysis device is shown in Figure 8 of the present application.

[0097] In FIG. 8, the dialysis machine (2000) comprises a disposable housing (10) having a fluid path in the form of a conduit (20) and a controller (31) in the form of a control housing (30) for controlling the operation of the disposable housing (10). The dialysis machine is powered by a battery (137). In this illustration, the disposable housing (10) and the control housing (30) are not operatively connected to each other. The disposable housing (10) and the control housing (30) comprise interfaces in the form of conduit connectors (40a, located on the control housing (30) and 40b, located on the disposable housing (10)) that can connect the control housing and the disposable housing. The disposable housing (10) and the control housing (30) are operatively engaged when the conduit connector (40a) is lockingly engaged with the conduit connector (40b). The conduit (20) of the disposable housing (10) is fluid-tightly sealed from the control housing (30) and the conduit connectors (40a, 40b).

[0098] The dialysis device includes a flexible dialysate tube (50) that can be in fluid communication with the peritoneal membrane (60) and the conduit (20). The dialysis device further includes a storage chamber (70) disposed within the rigid compartment (180). The storage chamber (70) includes a deformable diaphragm (71) integrally formed within one of the storage chamber's walls. The deformable diaphragm (71) is in fluid communication with the dialysate conduit (20) on one side and with a pressure chamber (80) on another, opposite side. When the disposable housing (10) and the control housing (30) are operably coupled to each other, the conduit connectors (40a, 40b) fluidly couple the pressure chamber (80) of the disposable housing (10) to a pump (90) disposed within the control housing (30). The conduit connectors (40a, 40b) include a first fitting portion (131f) and a second fitting portion (131s).

[0099] Pump (90) is configured to actuate deformable diaphragm (71) by inducing a pressure change in pressure chamber (80) that causes deformable diaphragm (71) to deform, thereby displacing dialysate in said dialysate conduit (20). Controller (31) includes computer (135) configured to actuate commands for operation of pump (90).

[0100] Check valves (101, 102, 103, 104) are disposed along the conduit (20) and are configured to, in an outflow mode, allow dialysate to flow from the peritoneal membrane (60) to the storage chamber (70), and, in an inflow mode, allow dialysate to flow from the storage chamber (70) to the sorbent zone (11) for removal of contaminants therein, and further allow dialysate substantially free of the contaminants to flow back into the peritoneal membrane (60).

[0101] The disposable housing also includes a concentrate module (12) in fluid communication with the conduit (20) via the conduit (13) for dispensing a preselected amount of concentrate solution into the dialysate. The concentrate module is also in fluid communication with the concentrate solution reservoir (121). The pump (90) is in fluid communication with the deformable membrane (72) of the concentrate module (12) via the conduit connectors (40a, 40b) when the disposable housing (10) and the control housing (30) are in operative engagement. The conduit connectors (40a, 40b) include a first mating portion (133f) and a second mating portion (133s).

[0102] An ammonia sensor (140) is also provided downstream of the sorbent zone (11) to detect ammonia present in the dialysate. Ammonia is detected by the ammonia detector (141) when the disposable housing (10) and the control housing (30) are operably coupled to one another.

[0103] A degasser in the form of a hydrophobic membrane (150) is also positioned downstream of the sorbent zone. The exterior side of the hydrophobic membrane (150) is in fluid communication with a vacuum pump (151) via conduit connectors (40a, 40b) when the control housing and disposable housing are operably coupled. As will be appreciated, the degasser may not be necessary when used with a filter device having degassing capabilities (e.g., filter devices 300, 302, 400).

[0104] 9-11 illustrate how a filter device of the present invention (eg, the single-chamber filter device depicted in FIG. 2) can be integrated into an embodiment of a peritoneal dialysis machine.

[0105] 9 depicts the integrated device in an outflow mode, showing the disposable housing (10) and control housing (30) operably coupled to one another, operating in outflow mode, where dialysate flow is directed from the patient's peritoneum (60) to the storage chamber (70). Pump (90) actuates deformable diaphragm (71) by inducing negative pressure within pressure chamber (80). The negative pressure within pressure chamber (80) deforms deformable diaphragm (71) by biasing it in the direction of arrow A, thereby displacing dialysate from the patient's peritoneum (60) through bubble trap (51) and into dialysate conduit (20). Dialysate flows through check valve (104) to the storage chamber (70). A pressure sensor (170) is disposed in operative communication with the pump (90) for establishing a preselected negative pressure in the pressure chamber (80) and for determining whether the pressure of the dialysate withdrawn from the peritoneum (60) is within safe limits.

[0106] Pump 90 operates intermittently under the control of pressure sensor 170 to maintain a negative pressure within a preselected range in pressure chamber 80. Once storage chamber 70 is filled with dialysate, this is detected by pressure sensor 170 and causes a reversal of pumping direction, thus converting the system to inflow mode.

[0107] Pump 90 is also in fluid communication with diaphragm 72 integrally formed in the wall of concentrate module 12. At the same time that storage chamber 70 is operated under negative pressure, concentrate module 12 is also operated under negative pressure by pump 90 such that a predetermined amount of concentrate solution is drawn from concentrate reservoir 121 into concentrate module 12 through check valve 103. Check valve 102 ensures that dialysate is not drawn from conduit 20 into concentrate module 12.

[0108] To integrate a single-chamber filter (200) into the embodiment of Figures 1A-1C of U.S. Patent Application Publication No. 2018 / 0147338, the filter, switch, bypass line, and associated tubing and connectors are installed between the bubble trap (51) and the conduit (20), as depicted in Figure 9. In outflow mode, spent dialysate flows from the peritoneal membrane (60) through the bubble trap (51) before entering the filtration circuit. Guided by switch (279), the spent fluid initially enters the first port (220) of the filter device (200). The spent fluid then enters the interior flow path of the hydrophilic hollow fibers (240). Negative pressure applied against the exterior surface of the plurality of hollow fibers transports water and low molecular weight solutes (<40 kDa) from the interior flow path of the plurality of hollow fibers (240) through the porous wall matrix to the exterior chamber (260) surrounding the exterior of the plurality of hollow fibers. Larger solutes, such as proteins and fibrin, are trapped on the luminal surfaces of the hollow fibers, preventing their interaction with the internal components of the purification system (i.e., sorbent 11). The filtered spent dialysate is then drawn from the second port (230) of the hollow fiber membranes by pump (90) through check valve (104) and via conduit (20) to storage chamber (70). The remainder of the dialysate treatment process is completed as described in U.S. Patent Application Publication No. 2018 / 0147338. The duration of the outflow mode in this case is governed by the flow rate at which storage chamber (70) is filled and the degree of filter clogging. An optional additional pressure sensor (235), located before (as shown) or within bubble trap (51), can be used to monitor the fluid pressure between the system and the patient to ensure that the patient line pressure remains within a safe operating range. While monitoring the pressure sensors (235 and 170), the system can then adjust the pump (90) to maintain sufficient negative pressure in the pressure chamber to ensure consistent and efficient regeneration of dialysate.

[0109] Figures 10 and 11 show an integrated device with a single chamber filter device (200) in the first stage (Figure 10) and second stage (Figure 11) in flow-through mode.

[0110] The inflow mode of the main dialysis system (2000) is the same in both Figures 10 and 11. In the inflow mode of Figure 10, the flow of dialysate is from the storage chamber (70) to the peritoneum (60). Once the storage chamber (70) is filled, the pump (90) actuates the deformable diaphragm (71) by inducing a positive pressure in the pressure chamber (80).

[0111] Positive pressure in pressure chamber (80) deforms deformable diaphragm (71) by biasing deformable diaphragm (71) in the direction of arrow B, thereby displacing dialysate from storage chamber (70) and check valve (104) closes, preventing the dialysate from returning to peritoneal membrane (60) before it has been treated to remove contaminants.

[0112] A pressure sensor (170) monitors the pressure in the pressure chamber (80) to ensure that the pressure of the dialysate returned to the peritoneum (60) in the inflow mode is within safe limits.

[0113] Dialysate flows from the storage chamber (70) through a check valve (101) into the sorbent zone (11). From the sorbent zone (11), the regenerated dialysate then flows past a deaerator in the form of a hydrophobic membrane (150). The exterior side of the membrane is subjected to negative pressure by a vacuum pump (151) to aid in the removal of gases generated during the dialysis procedure. The dialysate then flows through an ammonia sensor (140), which monitors the level of ammonia in the regenerated dialysate to ensure that the ammonia level does not exceed a safe limit, before returning it to the patient's peritoneum (60). The ammonia is detected by an ammonia detector (141).

[0114] The regenerated dialysate then flows past concentrate module 12. In inflow mode, pump 90, under positive pressure, operates diaphragm 72 of concentrate module 12, which has been previously primed with a volume of concentrate solution from concentrate reservoir 121. As concentrate module 12 operates, check valve 103 closes to ensure that concentrate solution does not backflow into concentrate reservoir 121. Concentrator module 12 then dispenses a preselected amount of concentrate solution containing desired substances, such as electrolytes, osmotic agents, nutrients, medications, etc., through check valve 102 and conduit 13 into dialysate conduit 20.

[0115] The regenerated dialysate then flows back through the bubble trap (51) and flexible dialysate conduit (50) into the peritoneal membrane (60).

[0116] As in the OUTFLOW mode, pump 90 is operated intermittently under the control of pressure sensor 170 to maintain a positive pressure within a preselected range in pressure chamber 80. Once the reservoir chamber is emptied of dialysate, pressure sensor 170 detects this and reverses the pumping direction, converting the system to OUTFLOW mode and repeating the dialysis cycle.

[0117] During the initial inflow washback phase (as shown in FIG. 10 ), regenerated fresh dialysate is transported from conduit (20) by pump (90) through switch 279 to second filter port (230). Downstream in conduit (20), the fresh dialysate encounters and mixes with spent dialysate from the preceding outflow. The mixture of fresh dialysate and spent dialysate (the combination of which constitutes the washback fluid) enters filter chamber (260) and exerts positive fluid pressure against the exterior surfaces of hollow fibers (240). This positive fluid pressure forces low molecular weight solutes, such as water, glucose, and electrolytes, through the porous wall matrix and through the interior flow paths of hydrophilic fibers (240). During this process, any proteins or biomaterials trapped on the fiber lumen are removed, defouling the inner pores of the fibers and restoring the original filter surface area. The washback fluid exits the filter through port (220), passes through the bubble trap (51), and re-enters the peritoneum (60). The volume of washback fluid (and thus the duration of the washback time) is optimized to ensure that the filter remains patent during the next flush cycle while minimal spent fluid is returned to the patient. An optional additional pressure sensor (299), located before (as shown) or within the bubble trap (51), can be used to monitor the fluid pressure between the system and the patient to ensure that the patient line pressure remains within a safe working range.

[0118] After the inflow washback phase ends, the inflow bypass phase begins, which is depicted in FIG. 11 . Regenerated fresh dialysate is transported from conduit (20) by pump (90) through switch 279 to bypass line 280. Downstream in conduit (20), the fresh dialysate encounters and mixes with a small amount of washback fluid from the preceding inflow washback cycle. Due to routing by switch 279, the majority of the fresh dialysate bypasses chamber 260 and instead passes through bubble trap (51) and re-enters peritoneum 9 directly via bypass line 280. The volume of the inflow bypass fluid is optimized to maximize fresh fluid return to the patient to maintain a sufficient dialysate / serum gradient for efficient toxin removal and electrolyte control. An optional additional pressure sensor 299, located before (as shown) or within bubble trap (51), can be used to monitor the fluid pressure between the system and the patient to ensure that the patient line pressure remains within a safe working range.

[0119] 18-20 illustrate how another embodiment of a filter device of the present invention (e.g., the double-chamber filter device depicted in FIG. 4) may be integrated into an embodiment of a peritoneal dialysis machine to provide a peritoneal dialysis system according to the present invention.

[0120] FIG. 18 depicts the integrated device in outflow mode. The main dialysis device (2000) is substantially identical to that depicted for FIG. 9, and therefore will not be described again for the sake of brevity. To integrate a double-chamber filter into the embodiment of FIGS. 1A-C of U.S. Patent Application Publication No. 2018 / 0147338, the filter, switch, bypass line, and associated tubing and connectors are installed between the bubble trap (51) and the conduit (20), as depicted in FIG. 18. Additionally, an air conduit (390) is installed to connect the pump air inlet (90a) to the filter's outlet port (318), thereby allowing the pump to draw air from the inlet port (317). This results in sweep gas flowing through chamber (315) under negative pressure during inflow. During outflow, the pump may expel air through (317) or another outlet, depending on the pump design. In alternative embodiments, an external source of suitably biocompatible sweep gas (e.g., an O2 / N2 mixture or purified compressed air), or a negative pressure source at 318, or a combination of both, may be provided.

[0121] In the OUTPUT mode (FIG. 18), spent dialysate flows from the peritoneal membrane (60) through the bubble trap (51) before entering the filtration circuit. Guided by switch (360), the spent fluid initially enters the first port 312 of the filter device 300. The spent fluid then enters the internal flow path of the hydrophilic hollow fibers 340. Negative pressure applied against the outer surface of the hollow fibers transports water and low molecular weight solutes (e.g., <40 kDa) from the internal flow path of the hollow fibers 340, through the porous wall matrix, and into the external chamber 311 surrounding the exterior of the hollow fibers. Again, note that positive pressure could be used instead to achieve the same effect. Larger solutes, such as proteins and fibrin, are trapped on the luminal surfaces of the hollow fibers, preventing their interaction with the internal components of the purification system 270. The filtered spent dialysate is then drawn by pump (90) through check valve (104) and conduit (20) to storage chamber (70) via second port 313 of the hollow fiber membrane. The remainder of the dialysate treatment process is completed as described in U.S. Patent Application Publication No. 2018 / 0147338. The duration of the outflow mode in this case is governed by the rate at which storage chamber (70) fills and the degree of filter clogging. An optional additional pressure sensor (335) located before (as shown) or within bubble trap (51) can be used to monitor the fluid pressure between the system and the patient to ensure that patient line pressure remains within a safe operating range. While monitoring pressure sensors (335 and 170), the system can then adjust pump (90) to maintain sufficient negative pressure in the pressure chamber to ensure consistent and efficient regeneration of dialysate.

[0122] 19 and 20 depict an integrated device with a dual chamber filter device 300 in the first stage (FIG. 19) and second stage (FIG. 20) of the inflow mode, also known as inflow washback and inflow bypass modes, respectively.

[0123] The inflow mode of the main dialysis system (2000) in Figures 19 and 20 is substantially the same as that depicted for Figures 10 and 11, and therefore this will not be described again for the sake of brevity.

[0124] During the initial inflow washback phase (as shown in FIG. 19 ), regenerated fresh dialysate is transported from conduit (20) by pump (90) through switch (320) to second filter port (313). Downstream in conduit (20), the fresh dialysate encounters and mixes with spent dialysate from the preceding outflow. The mixture of fresh dialysate and spent dialysate (the combination of which constitutes the washback fluid) enters filter chamber (311) and exerts positive fluid pressure against the exterior surfaces of hollow fibers (340). This positive fluid pressure forces water and low-molecular-weight solutes, such as glucose and electrolytes, through the porous wall matrix and through the interior flow paths of hydrophilic fibers (340). During this process, any proteins or biomaterials trapped on the fiber lumen are removed, defouling the inner pores of the fibers and restoring the original filter surface area. The washback fluid is routed through the headspace (330) and into the internal flow path of the hydrophobic fibers (350) contained within the second chamber (315). As described above, the washback fluid may be degassed by the use of a sweep gas via the inlet port (317), or negative pressure may be applied through the outlet port (318), or a combination thereof may be used. In FIG. 19, the pump (90) provides a constant flow of air under negative pressure at the output port (318), which degasses the fluid passing through the hydrophobic hollow fibers (350) within the chamber 315. The degassed washback fluid is removed through the filter through port 316, passes through the bubble trap (51), and re-enters the peritoneum (60) via the switch 360. The washback fluid volume is optimized to ensure that the filter remains patent during the next flush cycle while minimal spent fluid is returned to the patient. An optional additional pressure sensor (335) placed before (as shown) or within the bubble trap (51) can be used to monitor the fluid pressure between the system and the patient to ensure that the patient line pressure remains within a safe working range.

[0125] After the inflow washback phase ends, the inflow bypass phase begins, which is depicted in FIG. 20. Regenerated fresh dialysate is transported from conduit (20) by pump (90) to port 319 via switch 320. Routing by switch 320 causes the fluid to bypass first chamber (311) and instead enter the internal flow path of hydrophobic threads (350) enclosed within second chamber (315). Downstream of the purification system (e.g., sorbent 11), the fresh dialysate encounters and mixes with a small amount of washback fluid from the preceding inflow washback cycle. Most of the fresh dialysate enters the internal flow path of hydrophobic threads (350) and is degassed as described above. The degassed fresh dialysate then flows through filter outlet port 316, infuses through bubble trap (51), and re-enters peritoneum (60) via switch 360. The inlet bypass fluid volume is optimized to maximize fresh fluid return to the patient to maintain a sufficient dialysate / serum gradient for efficient toxin removal and electrolyte control. An optional additional pressure sensor 335 located before (as shown) or within the bubble trap (51) can be used to monitor the fluid pressure between the system and the patient to ensure that the patient line pressure remains within a safe working range.

[0126] As will be appreciated, the bubble trap may not always be necessary. While most automated peritoneal dialysis systems include a bubble trap or bubble sensor to prevent air from reaching the patient, not all forms of peritoneal dialysis incorporate such features. For example, continuous ambulatory peritoneal dialysis (CAPD), which involves the patient filling the bag by gravity, does not include a bubble trap or sensing mechanism. As such, a bubble trap may or may not be present in a peritoneal dialysis system that constitutes an embodiment of the present invention.

[0127] It will be understood that the above system may be configured to cooperate with the other filter devices disclosed herein. Additionally, it will be understood that other peritoneal dialysis systems may be configured (or designed) to function with the filter devices disclosed herein.

[0128] It will also be appreciated that the peritoneal dialysis filter device and post-filtration system may be provided as a kit of parts including both components, as described in more detail above in the Summary of the Invention section, but which is omitted here for the sake of brevity.

[0129] The filter device of the present disclosure may also be used in a hemodialysis system. In this regard, a hemodialysis machine 1000 (as shown in FIG. 12a) is also disclosed, which includes: A housing 1010, an exchange compartment 1020 having a blood inlet port 1021, a dialysate inlet port 1022, and a dialysate outlet port 1023; a blood degassing compartment 1030 having a blood outlet port 1031, a degassing gas inlet port 1032, and a negative pressure / gas outlet port 1033; a headspace cavity portion 1040 fluidly connecting the exchange compartment 1020 to the blood degassing compartment 1030; a housing 1010 comprising: a first hollow fiber membrane (1050) formed from a plurality of hydrophilic hollow fibers in the exchange compartment (1020) of the housing (1010), the plurality of hollow fibers having an inner surface and an outer surface, the inner surfaces of the plurality of hydrophilic hollow fibers being arranged coaxially with the arrangement of the blood inlet ports (1021) and the outer surfaces of the plurality of hollow fibers being arranged perpendicular to the arrangement of the dialysate inlet (1022) and outlet (1023) ports; a second hollow fiber membrane (1060) formed from a plurality of hydrophobic hollow fibers in the blood degassing compartment (1030) of the housing (1010), the plurality of hollow fibers having an inner surface and an outer surface, the inner surfaces of the plurality of hydrophobic hollow fibers being arranged coaxially with respect to the arrangement of the blood outlet ports (1031), and the outer surfaces of the plurality of hollow fibers being arranged perpendicular to the arrangement of the gas inlet ports (1032) and / or negative pressure ports (1033); The device may also include a device for regenerating the dialysate.

[0130] This embodiment will now be described by reference to Figures 13a and b. The device depicted in Figure 13a further includes a sorbent compartment 1070. In Figure 13a, dialysate fluid is continuously drawn from a dialysate reservoir 1071 and enters port 1072; the dialysate then passes through the sorbent in the sorbent compartment 1070. As it does so, it becomes fresh dialysate that exits port 1074. On its way to the exchange compartment 1020, the dialysate line is encountered by the infusate line, which then replenishes the essential cation Ca. 2+ , Mg 2+ , K. +The concentration of is returned to a predetermined level by the addition of a concentrate contained in the infusate module (infusate module and pump not shown). As will be appreciated, the infusate may simply be supplied by a concentrate bag (e.g., manually controlled). The regenerated dialysate then enters the exchange compartment 1020 via port 1022, thus passing over the outer surface of the hydrophilic hollow fibers 1050, while blood enters through port 1021 and flows in a parallel direction (because the fibers are coaxially arranged relative to port 1021) through the lumens of the fibers. As such, the dialysis process is carried out by a mass exchange mechanism between the blood and the dialysate. The cleansed blood passes over the headspace 1040 and enters the blood degassing compartment 1030, which contains the hydrophobic hollow fibers 1060. Again, the blood flows through the lumens of the fibers. In the blood degassing compartment 1030, the blood can be degassed before it is returned to the subject (via outlet port 1024) by using the sweep gas inlet 1032 and gas outlet 1033 and / or by applying negative pressure (through outlet 1033). As will be appreciated, the gas and / or negative pressure interacts directly with the exterior surfaces of the hollow fibers 1060. It will also be appreciated that if an oxygen-containing sweep gas is used, the blood can be infused with O to replace CO. Spent dialysate returns to the reservoir 1071 through the dialysate outlet port 1023. Pumps are used to control the flow of blood to and from the patient (pump 1091), direct the infusate to the infusate module (pump 1092), and return the spent dialysate to the dialysate reservoir (pump 1093). A top view of the filter device is shown in FIG. 13b.

[0131] The device 1000 depicted in Fig. 13a can be further integrated with other components into an embodiment of a hemodialysis system, as shown in Fig. 14. There is no difference in the operation of the filter device, which can be understood from the above description of Fig. 13a, and therefore will not be described in detail here.

[0132] FIG. 14 shows a hemodialysis machine 1100 that includes, among other components, the filter device 1000. Dialysate can be drawn from an external dialysate reservoir 1071 into a sorbent component 1070 via port 1072, controlled primarily by pump 1092. An infusate module, controlled by an infusate pump 1120, returns essential cations to the fresh dialysate flowing out of port 1074. Other control modules 1130 (such as heaters, flow meters, conductivity meters, thermometers, and ultrafiltration controllers) can be integrated in the dialysate flow path between the outlet port 1074 and the inlet port 1022 to monitor the properties of the regenerated dialysate before delivering it into the exchange compartment 1020. This can provide information about the efficiency and capacity of the sorbent in removing metabolic waste from the dialysate and when to replace the sorbent component or filter device.

[0133] After the exchange compartment 1020, the spent dialysate is pumped out and returned to the sorbent component 1070 via port 1072. Similarly, a control module 1140 (i.e., a blood leak detector and ultrafiltration meter) can be installed in the flow path between the outlet port 1023 and the inlet port 1072 to monitor the characteristics of the spent dialysate. This provides information about the health of the hydrophilic hollow fibers 1050 and whether cross-mixing of dialysate and blood has occurred. When the sorbent component 1070 is depleted, dialysate can be diverted from the dialysate reservoir 1071 through the bypass line 1150 to the inlet port 1022 of the exchange component 1020. Additionally, dialysate can be released from the dialysate reservoir 1071 (out of the housing 1100), which is controlled by the reservoir drain valve 1160 and the pump 1170.

[0134] In blood degassing component 1060, blood can be degassed before it is returned to the subject (through outlet port 1024) by using sweep gas inlet 1032 (from an external gas source) and gas outlet 1033 and / or by applying negative pressure (through outlet 1033). Gas can be released through gas outlet 1180 in the housing or by applying negative pressure at 1180.

[0135] In an alternative configuration, a further hemodialysis machine 1500 (as shown in FIG. 12b) is also disclosed herein, which comprises: a housing 1510, an exchange compartment 1520 having a blood inlet port 1521, a blood outlet port 1522, and a dialysate outlet port 1523; a dialysate degassing compartment 1530 having a dialysate inlet port 1531, a degassing gas inlet port 1532, and a negative pressure / gas outlet port 1533; a wall 1590 defining a fluid-impermeable boundary between the exchange compartment 1520 and the dialysate degassing compartment 1530; a dialysate fluid portal 1591 that allows dialysate to move from the dialysate degassing compartment 1530 to the exchange compartment 1520; a housing 1510 comprising: a first hollow fiber membrane 1550 formed from a plurality of hydrophilic hollow fibers in the exchange compartment of the housing, each of the plurality of hollow fibers having an inner surface and an outer surface, the inner surfaces of the plurality of hydrophilic hollow fibers being arranged coaxially with the arrangement of the blood inlet port and the outlet port, and the outer surfaces of the plurality of hollow fibers being arranged perpendicular to the arrangement of the dialysate outlet ports 1523; a second hollow fiber membrane 1560 formed from a plurality of hydrophobic hollow fibers in the dialysate degassing compartment of the housing, each of the plurality of hollow fibers having an inner surface and an outer surface, the inner surfaces of the plurality of hydrophobic hollow fibers being arranged coaxially with the arrangement of the degassing gas input port 1532 and the negative pressure / gas outlet port 1533, and the outer surfaces of the plurality of hollow fibers being arranged perpendicular to the arrangement of the dialysate inlet port 1531 and the dialysate fluid portal 1591; The device may also include a device for regenerating the dialysate.

[0136] It will be understood that this embodiment operates by analogy to that described above. That is, dialysate flows through inlet port 1531 into the degassing chamber, where it is degassed through the use of a sweep gas (e.g., air, oxygen, or a mixture of air and other gases, such as nitrogen) so that unwanted gases (e.g., CO) are at least partially replaced with oxygen. Degassing gas passes through the lumens of the hydrophobic hollow fibers 1560, while the dialysate encounters only the outer surfaces of the hydrophobic hollow fibers 1560. The degassing chamber 1530 is separated from the exchange chamber by a fluid-impermeable wall 1590, which includes a fluid portal 1591 in its upper region. As will be understood, instead of a portal through part of the wall, the wall could instead be formed as a weir. To enter exchange chamber 1520, dialysate flows through fluid portal 1591 and thus into the exchange chamber, where it passes over the outer surface of the hydrophilic hollow fibers, while blood enters through port 1521 and flows in a parallel direction (because the fibers are coaxially disposed relative to port 1051) through the lumen of the fibers. As such, the dialysis process occurs by a mass exchange mechanism between the blood and dialysate fluid. The cleansed blood is then allowed to exit through blood outlet port 1522. As will be appreciated, the general functionality of the filter device depicted in FIG. 12b is the same as that depicted in FIG. 12a, and features not described above may be considered to be incorporated by analogy, if desired.

[0137] A further hemodialysis device 1501 (as shown in Figures 15a and b) is also disclosed, which includes: a housing 1510, an exchange compartment 1520 having a blood inlet port 1521, a blood outlet port 1522, a first dialysate inlet port 1591b, and a first dialysate outlet port 1523; a dialysate degassing compartment 1530 having a second dialysate inlet port 1531, a second dialysate outlet port 1591a, a degassing gas inlet port 1532, and a negative pressure / gas outlet port 1533; a wall 1590 defining a fluid-impermeable boundary between the exchange compartment 1520 and the dialysate degassing compartment 1530; a housing 1510 comprising: a first hollow fiber membrane 1550 formed from a plurality of hydrophilic hollow fibers in the exchange compartment of the housing, each of the plurality of hollow fibers having an inner surface and an outer surface, the inner surfaces of the plurality of hydrophilic hollow fibers being arranged coaxially with the arrangement of the blood inlet port 1521 and the outlet port 1522, and the outer surfaces of the plurality of hollow fibers being arranged perpendicular to the arrangement of the first dialysate inlet port 1591b and the outlet port 1523; a second hollow fiber membrane 1560 formed from a plurality of hydrophobic hollow fibers in the dialysate degassing compartment 1530 of the housing, each of the plurality of hollow fibers having an inner surface and an outer surface, the inner surfaces of the plurality of hollow fibers being arranged coaxially with the arrangement of the second dialysate inlet port 1531 and the outlet port 1591a, and the outer surfaces of the plurality of hollow fibers being arranged perpendicular to the arrangement of the degassing gas inlet port 1532 and / or the negative pressure / gas outlet port 1533; and optionally, the device further comprises a device for regenerating dialysate 1570.

[0138] This embodiment will now be described with reference to Figures 15a and b. The device depicted in Figure 15a further includes a sorbent compartment 1570. Dialysate fluid is continuously drawn from a dialysate reservoir 1571 and enters port 1572, which then passes through the sorbent in sorbent compartment 1573 and becomes fresh dialysate that exits through port 1574. On its way to the degassing compartment 1530, the dialysate line is encountered by the infusate line, which removes the essential cation Ca. 2+ , Mg 2+ , K. + The concentration of is returned to a predetermined level by the addition of concentrate contained within the infusate module (infusate module and pump not shown). As will be appreciated, the infusate may simply be supplied by a concentrate bag (e.g., manually controlled). The replenished fluid then enters (via port 1531) the degassing compartment 1530, which houses the hydrophobic hollow fibers 1560, where it may be degassed by using the sweep gas inlet 1532 and gas outlet 1533 and / or by applying negative pressure (through outlet 1533). Again, as will be appreciated, if an oxygen-containing sweep gas is used, the blood may be infused with O to replace CO. Fresh dialysate then exits through dialysate fluid portal 1591a and enters the exchange compartment 1520 through dialysate fluid portal 1591b, where blood passes through the lumen of the hydrophobic hollow fibers 1550 following entry through blood inlet port 1521. As previously described, the dialysis process occurs by a mass exchange mechanism between the blood and the dialysate. The blood then exits through blood outlet port 1522, and the spent dialysate fluid returns to the dialysate reservoir through dialysate outlet port 1523. Pumps are used to control the flow of blood to and from the patient (not shown), transport the dialysate towards the infusate module (if such a module is present; pump 1592), and return the spent dialysate to the dialysate reservoir (pump 1593). A top view of filter device 1501 is shown in Figure 15b.

[0139] The filter device 1501 depicted in Fig. 15a can be further integrated with other components into an embodiment of a hemodialysis system as shown in Fig. 16. There is no difference in the operation of the filter device, which can be understood from the above description of Fig. 15a, and therefore will not be described in detail here.

[0140] FIG. 16 shows a hemodialysis machine housing 1600 that includes, among other components, a filter device 1501. Dialysate can be drawn from an external dialysate reservoir 1571 into a sorbent component 1570 through port 1572, controlled primarily by pump 1592. Fresh dialysate flowing out of port 1574 is then replenished with necessary nutrients by the infusate module, controlled by infusate pump 1620. The replenished fluid then enters a degassing compartment 1530 (through port 1531), which contains hydrophobic hollow fibers 1560, where it is degassed using sweep gas inlet 1532 and gas outlet 1533 and / or by applying negative pressure (through outlet 1533). Gas can be supplied or released through a gas outlet 1680 within the housing. Fresh dialysate then exits through dialysate outlet 1591 a and enters exchange compartment 1520 through dialysate inlet 1591 b. Other control modules 1630 (such as heaters, flow meters, conductivity meters, thermometers, and ultrafiltration controls) can be integrated in the dialysate flow path between dialysate outlet 1591 a and inlet 1591 b to monitor the properties of the regenerated dialysate before it enters exchange compartment 1520. This provides information about the efficiency and capacity of the sorbent in removing metabolic waste products from the dialysate and when to replace the sorbent component or filter device.

[0141] After exchange compartment 1020, the spent dialysate is pumped (i.e., controlled by pump 1593) and returned to sorbent component 1570 via port 1572. Similarly, control module 1640 (i.e., a blood leak detector and ultrafiltration meter) can be installed in the flow path between outlet port 1523 and inlet port 1572 to monitor the characteristics of the spent dialysate. This provides information about the health of hydrophilic hollow fibers 1550 and whether cross-mixing of dialysate and blood has occurred. When sorbent component 1570 is depleted, dialysate can be flowed from dialysate reservoir 1571 through bypass line 1650 to inlet port 1531 of degassing component 1530. Additionally, if necessary, dialysate can be released from dialysate reservoir 1571 (outside housing 1600), controlled by reservoir drain valve 1660 and pump 1670.

[0142] In the degassing component 1530, the dialysate can be degassed before it is flowed into the exchange compartment 1520 (via outlet port 1591 a and inlet port 1591 b) by using a sweep gas inlet 1532 (from an external gas source) and gas outlet 1533 and / or by applying negative pressure (through outlet 1680). As will be appreciated, if an oxygen-containing sweep gas is used, the blood can be infused with O to replace CO. The oxygenated dialysate is then flowed into the exchange compartment 1520, allowing oxygen to be transferred to the blood flowing through the hydrophilic threads 1550. The cleansed, oxygenated blood can then exit through blood outlet port 1522 and be returned to the subject.

[0143] The filters described herein have several advantages that allow them to enhance existing dialysis therapies, including improvements in clinical effectiveness and device efficiency in peritoneal dialysis, hemodialysis, and ICU continuous renal replacement therapy (CRRT) dialysis. These advantages may include, but are not limited to: (1) Improved treatment safety and functionality (i.e., CO2 / O2 control). The filters disclosed herein can also provide degassing and / or oxygenation functions for the dialysis machine to which they are attached. Making these features integral functions of the filters disclosed herein provides additional treatment options and minimizes the overall machine footprint (i.e., by eliminating the need for separate degassing or oxygenation devices, thereby reducing the overall footprint of the system required to provide treatment), while reducing safety risks to subjects using the machine. A reduced machine footprint is one of the most important factors in the development of wearable dialysis machines and for use in intensive care unit (ICU) environments, which often have tight space budgets. (2) Improved therapeutic efficacy (i.e., PBUT removal). The filter solutions disclosed herein utilize a non-drug dependent method for removing PBUT. This can be achieved by adding an activated charcoal filter in the inflow path before the dialysate refluxes into the peritoneal membrane, as described in further detail herein. (3) Improved therapeutic efficiency (i.e., the filters disclosed herein can be operated using novel washback techniques that counteract and prevent clogging of the flow channels (e.g., by binding proteins and / or excreted leukocytes). A further advantage of these techniques is that they are expected to reduce protein loss in subjects undergoing PD. Because the methods disclosed herein allow more protein to remain in the subject's peritoneum, this may slow the transport of proteins from the bloodstream to the peritoneum. This may reduce protein loss suffered by the subject and help prevent malnutrition, or at least avoid exacerbating any existing malnutrition suffered by the subject. Thus, standard and advanced adaptive washback techniques that attempt to achieve optimized flow conditions within the entire device are also disclosed herein.

[0144] As described above, each cycle begins with an outflow phase followed by an inflow phase. The inflow phase includes a washback phase, in which a portion of the regenerated dialysate passes through the hydrophilic threads of the filter device, and a bypass phase, in which the remaining regenerated dialysate (most of it) returns directly to the subject's peritoneum without passing through the hydrophilic threads of the filter device. The filter device may be any one of the filter devices with hydrophilic threads described above, such as filter devices 200, 300, 302, 400, 1000, 1500, or 1501. The washback phase is necessary because proteins are trapped in the hydrophilic threads over several cycles, and the washback fluid helps to flush out these trapped proteins that clog the filter device. The volume of washback fluid (and therefore the duration of the washback time) during the washback phase is optimized to ensure that the filter remains patent during the next cycle while minimal spent fluid is returned to the subject.

[0145] A standard washback procedure can be implemented so that the amount of washback fluid is constant from cycle to cycle. This should ensure that at least 90% of the captured protein is washed back into the subject, with a maximum protein loss of less than 10% over the entire treatment period. Once at least 90% of the protein has been washed back, increasing the washback volume does not significantly improve washback efficiency.

[0146] Because some proteins cannot pass through the hydrophilic threads and remain trapped, more proteins accumulate within the hydrophilic threads over time, increasingly clogging the filter device. Proteins can also accumulate if a subject's peritoneal excretion of proteins is higher than normal. The flow rate through the hydrophilic threads decreases due to the greater flow resistance from the accumulated proteins, and the time required to complete the entire inflow and outflow phases of the subsequent cycle increases accordingly. In this scenario, a standard washback technique using a fixed amount of washback fluid is not sufficient to effectively washback all of the proteins trapped within the filter device. Instead, an advanced adaptive washback technique can be implemented in which the amount of washback fluid can be adjusted depending on the clogging profile of the filter device. In particular, a filter device with clogged hydrophilic threads may require a larger amount of washback fluid compared to a new filter device.

[0147] An embodiment of this advanced adaptive washback technique can be expressed as a method for controlling dialysate flow in a peritoneal dialysis system. The method is performed by a processor that adjusts the amount of washback fluid based on a clogging profile of a filter device. The processor is configured to execute instructions, code, computer programs, and / or scripts and includes suitable logic, circuitry, and / or interfaces for carrying out such instructions.

[0148] The method includes determining a number of outflow and / or inflow parameters of dialysate from a subject flowing between a filter device and a sorbent device over one or more cycles, each cycle having an outflow phase and an inflow phase. The parameters may include the outflow and inflow volumes of dialysate passing through the filter device during the outflow and inflow phases, respectively. If the dialysate volume is fixed, one of the flow rate and flow duration may be determined from the other. The flow rate may be measured using a volumetric flow sensor. The time required for the dialysate to pass through the filter device and complete each outflow and inflow phase may be tracked using a level sensor in the reservoir. A pressure sensor may also be used to estimate the flow resistance and clogging status of the filter device (e.g., by the percentage of clogging).

[0149] Each sensor transmits a parameter to a processor for processing to derive other parameters characterizing the inflow / outflow profile, such as flow rate, flow pressure, and flow duration. The method includes comparing the parameters to a set of predefined conditions for controlling the flow of dialysate through a filter device comprising hydrophilic threads. In this step, the processor uses a preprogrammed algorithm to compare the parameters to the predefined conditions. Some examples of these parameters and predefined conditions are described below.

[0150] The method includes allocating regenerated dialysate to flow from the sorbent device to the filter device during an inflow phase based on the comparison of the parameters, and passing the allocated regenerated dialysate through hydrophilic threads of the filter device, wherein the processor calculates an amount of regenerated dialysate to allocate to the washback phase based on the comparison.

[0151] The method includes controlling a switching means or device to deliver an allocated portion of regenerated dialysate to the hydrophilic yarns of the filter device (for the inflow washback phase). After the allocated portion of regenerated dialysate has been delivered, the switching means or device returns the remaining regenerated dialysate to the subject (for the outflow bypass phase) without passing through the hydrophilic yarns of the filter device. In this step, the processor sends a control signal to the switching means or device to deliver the allocated portion of regenerated dialysate for washback. The switching means or device selects delivery of the regenerated dialysate to the hydrophilic yarns of the filter device or to the bypass fluid path.

[0152] Therefore, if the parameters meet predefined conditions established based on the standard parameters of a fresh or unclogged filter device, the regenerated dialysate is allocated accordingly to adjust the amount of washback fluid. In particular, if the filter device is clogged, the allocated regenerated dialysate is increased to increase the amount of washback fluid returned to the filter device. The allocated regenerated dialysate may be returned from the reservoir at a standard flow rate so that the washback duration is increased, or may be returned at a higher flow rate for the same washback duration. A higher flow rate may improve the removal of trapped proteins from the filter device. The allocated regenerated dialysate may be delivered in various flow patterns, such as continuous flow or pulsatile flow. Characteristics that affect the flow pattern, particularly pulsatile flow (e.g., frequency, amplitude, and duration), may be pre-calibrated but may be adjusted based on the parameters and predefined conditions. For example, a specific clogging profile of the filter device may require a specific flow pattern.

[0153] A larger amount of allocated, regenerated dialysate should improve washing of trapped proteins and clean the filter device. If one cycle is not sufficient to effectively clean the filter device with the adaptive washback technique, the adaptive washback technique can be implemented over multiple cycles to continuously remove trapped proteins from the filter device, eventually returning it to or near the standard parameters of a fresh or unclogged filter device. The amount of regenerated dialysate in one of these multiple cycles can be allocated further based on the amount of allocated, regenerated dialysate in one or more previous cycles. Continuously cleaning the hydrophilic threads using this adaptive washback technique can extend the life of the filter device.

[0154] In one example, the parameters include the amount of dialysate flowing through the filter device during the outflow phase of the current cycle. The amount of outflow can be determined from the outflow duration, or vice versa. The predefined conditions can set a standard duration for the outflow phase and for a fixed dialysate volume. The standard outflow duration can be 5 minutes, with a corresponding washback duration of 10 seconds. If the filter device is clogged, the outflow duration increases depending on the degree of clogging. If the outflow duration increases to 5.5 minutes, the washback duration can be increased to 15 seconds. If the outflow duration increases to 6 minutes, the washback duration can be increased to 20 seconds. Increasing the washback duration means that a larger portion of the regenerated dialysate is sent back to the filter device as washback fluid during the inflow phase of the current cycle.

[0155] The parameters may further comprise the outflow and / or inflow volume of dialysate passing through the filter device during the outflow and / or inflow phases, respectively, of the preceding cycle. Considering the flow rate of the preceding cycle, or of a series of past cycles, helps to establish the clogging trend, and the regenerated dialysate of the subsequent cycle may be allocated accordingly, for example, depending on the rate or slope of the increasing clogging trend.

[0156] In one example, the parameters include the inflow volume during the inflow phase of the previous cycle and the outflow volume during the outflow phase of the current cycle. The standard durations of the inflow and outflow phases may be 2.5 minutes and 5 minutes, respectively, corresponding to a washback duration of 10 seconds. If the previous inflow duration increases to 3 minutes and the current outflow duration increases to 5.5 minutes, the washback duration may be increased to 15 seconds. If the previous inflow duration increases to 3.5 minutes and the current outflow duration increases to 7 minutes, the washback duration may be increased to 20 seconds.

[0157] In one example, the parameters include the outflow volumes during the outflow phase of the previous and current cycles, and the predefined condition is associated with the difference between the outflow volumes. This difference between the outflow volumes represents the degree or slope of the clogging tendency. If the difference exceeds a predefined threshold (e.g., 0.5 minutes or a percentage between the previous and current cycles, e.g., 10%) and / or the current outflow duration exceeds a predefined duration (e.g., 5.5 minutes), this indicates that the filter device is becoming clogged, and an adaptive washback strategy is triggered to allocate regenerated dialysate to the washback phase of the inflow phase of the current cycle.

[0158] In one example, the parameters include inflow rates during the inflow phases of the previous and current cycles, and a predefined condition is associated with the difference between the inflow rates. If the difference exceeds a predefined threshold (e.g., 0.5 minutes or a percentage between the previous and current cycles, e.g., 10%) and / or the current inflow duration exceeds a predefined threshold (e.g., 3 minutes), an adaptive washback technique is triggered to allocate regenerated dialysate to the washback phase of the inflow phase of the next cycle.

[0159] While specific values ​​of parameters for predefined conditions are described above, it will be understood that these parameters may have different values ​​and that these values ​​may be interpolated depending on the predefined conditions. As an example, the outflow duration of a current cycle (first cycle) is 5.5 minutes due to clogging, and the washback duration is adjusted to 15 seconds during the inflow phase of the first cycle. The outflow duration of the next cycle (second cycle) may be slightly reduced to 5.3 minutes, still at the standard 5 minutes, due to certain remaining clogging. The washback duration during the inflow phase of the second cycle is not yet reduced to the standard 10 seconds, but instead may be adjusted based on the washback duration (15 seconds) of the previous cycle (first cycle). Specifically, the washback duration of the second cycle may be adjusted to an intermediate interpolated value, e.g., 13 seconds.

[0160] It will also be appreciated that the predefined conditions may set different conditions for parameters that determine the allocation of regenerated dialysate. For example, the predefined conditions may consider a series of two or more previous cycles to determine a clogging tendency and allocate the regenerated dialysate accordingly. The standard parameters and predefined conditions may also depend on the type of hydrophilic yarn used in the filter device. For example, some hydrophilic yarns may have different standard flow rates for the filter device to operate effectively. Some hydrophobic yarns may be more susceptible to clogging and may require more stringent conditions for the adaptive washback approach.

[0161] Furthermore, the modular nature of the various components of the filter system allows for flexibility in combining components depending on the needs of the system. This allows for a wide range of products to be obtained for various purposes. The different components of current filter systems required for different products (non-sorbent and sorbent-based) are summarized in Tables 1 and 2, respectively.

[0162] [Table 1]

[0163] [Table 2] TIFF0007728339000003.tif24297

Claims

1. 1. A device for use in peritoneal dialysis, said device comprising: (i) a filter device; (ii) a post-filtration system; The filter device comprises: a housing having a first port and a second port; a hollow fiber membrane formed from a plurality of hydrophilic hollow fibers within the housing; and Equipped with each of the plurality of hollow fibers has an inner surface and an outer surface; the hydrophilic hollow fibers have a porous wall matrix; the inner surfaces of the plurality of hydrophilic hollow fibers are arranged coaxially with respect to the arrangement of the first ports, and the outer surfaces of the plurality of hollow fibers are arranged perpendicular to the arrangement of the second ports; When used, Dialysate from a subject enters the filter device through the first port, is filtered through the porous wall matrix, and the filtered dialysate exits in an outflow direction via the second port; and regenerated dialysate from a sorbent system enters the filter device through the second port, passes through the porous wall matrix, and exits in an inflow direction via the first port; the post-filtration system comprising: (a) a switch; (b) a post-filtration sorbent compartment; (c) a fluid connection connecting the post-filtration sorbent compartment, the switch, and the first port of the housing; It is composed of The post-filtration system and the filter device together a first fluid path defined by the first port of the housing, the switch, and a fluid connection therebetween; a second fluid path defined by the first port of the housing, the switch, a post-filtration sorbent compartment, and a fluid connection therebetween; Forming the switch is adapted to select between the first fluid path and the second fluid path; the first fluid path and the second fluid path are both fluidly connected to the first port of the housing through the switch; the post-filtration sorbent compartment comprises a post-filtration sorbent suitable for removing one or more of water-soluble uremic toxins, protein-bound uremic toxins, low molecular weight proteins, endotoxins, exotoxins, inflammatory mediators, and microorganisms; Device.

2. the first fluid path is connectable to the subject's peritoneum via the switch; the second fluid pathway is connectable to the subject's peritoneum via the post-filtration sorbent compartment; 10. The apparatus of claim 1.

3. 1. A peritoneal dialysis system, comprising: a filter device; Adsorbent device and Equipped with the filter device is configured to receive and filter entire dialysate from a subject and, when operating in an outflow direction, to supply the filtered dialysate to the sorbent device; the filter device is configured to receive at least a portion of the regenerated dialysate from the sorbent device when operating in an inflow direction; The filter device a housing having a first port and a second port; a hollow fiber membrane formed from a plurality of hydrophilic hollow fibers within the housing, each of the plurality of hollow fibers having an inner surface and an outer surface; Equipped with the hydrophilic hollow fibers have a porous wall matrix; the inner surfaces of the plurality of hydrophilic hollow fibers are aligned coaxially with respect to the first port, and the outer surfaces of the plurality of hollow fibers are aligned perpendicularly with respect to the second port; When used, the dialysate from the subject enters the filter device through the first port, is filtered through the porous wall matrix, and the filtered dialysate exits in an outflow direction via the second port; and regenerated dialysate from the sorbent device enters the filter device through the second port, passes through the porous wall matrix, and exits in an inflow direction via the first port; The filter device further comprises a post-filtration system, the post-filtration system comprising: a first fluid path that does not include a post-filtration compartment; a second fluid path comprising a post-filtration compartment; a switch for selecting between the first fluid path and the second fluid path; Equipped with the first fluid path is disposed between the first port of the housing and the switch and is connectable to a peritoneum of the subject; the second fluid path is disposed between the first port of the housing, the switch, and the post-filtration sorbent compartment, and is further connectable to the subject's peritoneum; the post-filtration compartment comprises a post-filtration sorbent suitable for removing one or more of water-soluble uremic toxins, protein-bound uremic toxins, low molecular weight proteins, endotoxins, exotoxins, inflammatory mediators and microorganisms; Peritoneal dialysis system.

4. 1. A peritoneal dialysis system, comprising: a filter device; Adsorbent device and Equipped with the filter device is configured to receive and filter entire dialysate from a subject and, when operating in an outflow direction, to supply the filtered dialysate to the sorbent device; the filter device is configured to receive at least a portion of the regenerated dialysate from the sorbent device when operating in an inflow direction; The filter device A housing, a first compartment having a first port and a second port; a second compartment having a third port, an inlet port, and an outlet port; a switching means or device fluidly connected to the first port and the third port and configured to be connected to the peritoneum of a subject; a headspace cavity fluidly connecting the first compartment to the second compartment; a housing comprising: a first hollow fiber membrane formed from a plurality of hydrophilic hollow fibers in the first compartment of the housing, each of the plurality of hollow fibers having an inner surface and an outer surface, the inner surfaces of the plurality of hydrophilic hollow fibers being arranged coaxially with respect to the arrangement of the first ports, and the outer surfaces of the plurality of hollow fibers being arranged perpendicular to the arrangement of the second ports; a second hollow fiber membrane formed from a plurality of hydrophobic hollow fibers in the second compartment of the housing, each of the plurality of hollow fibers having an inner surface and an outer surface, the inner surfaces of the plurality of hydrophobic hollow fibers being arranged coaxially with respect to the arrangement of the third ports, and the outer surfaces of the plurality of hollow fibers being arranged perpendicular to the arrangement of the inlet ports and / or the outlet ports; Equipped with the hydrophilic hollow fibers have a porous wall matrix; During use, the dialysate from the subject enters the first compartment of the filter device through the first port and exits the first compartment of the filter device in an outflow direction via the second port; and regenerated dialysate from the sorbent device enters the first compartment of the filter device through the second port and passes through the headspace cavity to the second compartment, the plurality of hydrophobic hollow fibers degassing the regenerated dialysate before it exits through the third port, and the removed gas exits the filter device via the outlet port. Peritoneal dialysis system.

5. The filter device further comprises a post-filtration system, the post-filtration system comprising: (a) a fluid pathway disposed between the third port of the housing and the switching means or device, the fluid pathway comprising a post-filtration sorbent compartment, the post-filtration sorbent compartment comprising a sorbent suitable for removing one or more of water-soluble uremic toxins, protein-bound uremic toxins, low molecular weight proteins, endotoxins, exotoxins, inflammatory mediators, and microorganisms; and / or (b) further comprising a post-filtration sorbent disposed within the headspace cavity, the sorbent being suitable for removing one or more of water-soluble uremic toxins, protein-bound uremic toxins, low molecular weight proteins, endotoxins, exotoxins, inflammatory mediators, and microorganisms; The peritoneal dialysis system of claim 4.

6. The peritoneal dialysis system further comprises a bypass means or a bypass device, the bypass means or the bypass device comprising: (a) a bypass fluid pathway connected to the sorbent device and configured to return regenerated dialysate to the subject without passing through any portion of the filter device; a switching means or device for selecting between sending regenerated dialysate to the filter device or to the bypass fluid path; or (b) a bypass fluid pathway connected to the sorbent device and configured to return regenerated dialysate to the subject through the second compartment of the filter device having a fourth port, the bypass fluid pathway including the dialysate entering the second compartment through the fourth port and exiting through the third port; a switching means or device for selecting between delivering regenerated dialysate to the second port or the fourth port of the filter device; Equipped with The peritoneal dialysis system according to claim 4 or 5.

7. The peritoneal dialysis system further comprises a bypass means or a bypass device, the bypass means or the bypass device comprising: a bypass fluid pathway connected to the sorbent device and configured to return regenerated dialysate to the subject without passing through the filter device; a switching means or device for selecting between sending regenerated dialysate to the filter device or to the bypass fluid path; Equipped with The peritoneal dialysis system according to any one of claims 3 to 6.

8. 1. A kit of parts, said kit of parts comprising: (a) a peritoneal dialysis filter device according to claim 1; (b) a post-filtration system; wherein the post-filtration system comprises: (i) a switch; (ii) a post-filtration sorbent compartment; (iii) a fluid connection connecting the post-filtration sorbent compartment and the switch; It consists of the switch of the post-filtration system and the first port of the housing of the filter device; a first fluid path defined by the first port of the housing, the switch, and a fluid connection therebetween; a second fluid path defined by the first port of the housing, the switch, the post-filtration sorbent compartment, and a fluid connection therebetween; and the switch is adapted to select between the first fluid path and the second fluid path; the first fluid path and the second fluid path are both fluidly connected to the first port of the housing through the switch; the post-filtration sorbent compartment comprises a post-filtration sorbent suitable for removing one or more of water-soluble uremic toxins, protein-bound uremic toxins, low molecular weight proteins, endotoxins, exotoxins, inflammatory mediators, and microorganisms; Kit of parts.

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