Sorbent cartridges for processing dialysates

Abstract

In some examples, a sorbent cartridge is configured to hydrolyze urea in a dialysate. The sorbent cartridge may include a substrate including a mesh. The sorbent cartridge may further include a urea hydrolyzing species covalently linked to the mesh of the substrate. In some examples, a technique may include covalently linking a urea hydrolyzing species to a mesh of a substrate of a sorbent cartridge.

Description

Docket No.: MZM00005 PCT / 1246-069W001SORBENT CARTRIDGES FOR PROCESSING DIALYSATESCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] The present application claims the benefit of U.S. Provisional Application Serial No. 63 / 746,505, filed January 17, 2025, which is incorporated herein by reference in entirety.TECHNICAL FIELD

[0002] The present disclosure generally relates to dialysis, and to sorbent cartridges for processing dialysates.BACKGROUND

[0003] Dialysis includes passing a dialysate through a dialyzer including a membrane to remove waste and solutes from a fluid to be dialyzed (e.g., from a patient). After the dialysate receives waste and solutes, the loaded dialysate can be passed through a sorbent cartridge to remove waste and solutes from the dialysate. After the waste and solutes are removed, the dialysate can be recirculated back to the dialyzer.SUMMARY

[0004] In general, the present disclosure describes sorbent cartridges for processing dialysates used in dialysis. A dialysis fluid may carry wastes from a patient. The dialysis fluid containing wastes removed from the patient may be transported to a dialyzer. In the dialyzer, the wastes are transferred from the dialysis fluid to a dialysate through a membrane to clean the dialysis fluid. The dialysis fluid may be recirculated to the patient. After the wastes are received in the dialysate, the dialysate may be processed by passing through a sorbent cartridge to extract the wastes from the dialysate. The waste-free dialysate may be recirculated to the dialyzer to continue extracting further waste from the dialysis fluid.

[0005] The wastes to be extracted from the dialysate by the sorbent cartridge may include urea. The sorbent cartridge may include a urea hydrolyzing species (e.g., a urease) configured to hydrolyze the urea into ammonia, which may be captured or removed by the sorbent cartridge. Fluid flow through the sorbent cartridge may tend to remove or transport the urea hydrolyzing species away from the sorbent cartridge. In some examples, the urea hydrolyzing species is immobilized on or within a substrate to promote the retention of the urea hydrolyzing species within the sorbent cartridge.Docket No.: MZM00005 PCT / 1246-069W001

[0006] In some examples, an example sorbent cartridge is configured to hydrolyze urea in a dialysate. The sorbent cartridge may include a substrate including a mesh. The sorbent cartridge may further include a urea hydrolyzing species covalently linked to the mesh of the substrate.

[0007] In some examples, an example technique includes covalently linking a urea hydrolyzing species to a mesh of a substrate of a sorbent cartridge.

[0008] The details of one or more examples of the techniques of this disclosure are set forth in the accompanying drawings and the description below. Other features, objects, and advantages of the techniques will be apparent from the description and drawings, and from the claims.BRIEF DESCRIPTION OF DRAWINGS

[0009] FIG. 1 A is a conceptual diagram illustrating a dialysis system comprising a dialyzer fluidly coupled to a sorbent cartridge configured to hydrolyze urea in dialysate from the dialyzer.

[0010] FIG. IB is a conceptual diagram illustrating a partial side view of a substrate and a urea hydrolyzing species covalently linked to the substrate.

[0011] FIG. 2 is a conceptual diagram illustrating a mesh comprising a plurality of mesh layers.

[0012] FIG. 3 is a conceptual diagram illustrating a mesh layer comprising a woven mesh body.

[0013] FIG. 4 is a conceptual diagram illustrating a mesh layer comprising a non-woven mesh body.

[0014] FIG. 5 is a flow diagram illustrating an example technique for forming a sorbent cartridge.DETAILED DESCRIPTION

[0015] The present disclosure generally relates to sorbent cartridges for processing dialysates. One type of dialysis for the treatment of kidney failure is hemodialysis.Hemodialysis may be performed in clinical or non-clinical locations (e.g., at a residence) for a patient. In dialysis, waste products are extracted from a dialysis fluid to a dialysate in a dialyzer. In conventional hemodialysis, the waste-loaded dialysate is disposed (single-pass of dialysate). In multi-pass or sorbent-based dialysis, the dialysate is processed to remove wasteDocket No.: MZM00005 PCT / 1246-069W001from the dialysate, and the dialysate is then recirculated to extract further waste. For example, the dialysate is processed by flowing the dialysate through a sorbent cartridge to extract the waste products received by the dialysate into the sorbent cartridge. For example, the sorbent cartridge may include one or more substrates or layers configured to remove one or more waste products from the dialysate. In some examples, the waste products include urea, and the sorbent cartridge may include a substrate configured to extract urea from the dialysate by hydrolysis (e.g., converting the urea into ammonia, which is removed from the dialysate into the sorbent cartridge). For example, the substrate may include a urea hydrolyzing species (e.g., a urease).

[0016] The efficiency of hydrolysis (e.g., by a reaction catalyzed by urease) in breaking down urea may be limited by exposure of the substrate to the urea hydrolyzing species, migration of the urea hydrolyzing species during treatment, and presence of ions (e.g., copper and / or silver) or other contaminants in the water used for treatment that reduce the effectiveness of the hydrolyzing species. Urea hydrolyzing species such as urease are water soluble, and would dissolve in the dialysis fluid and migrate out of the sorbent cartridge if not physically bound to a substrate. A substrate that strongly binds urease, such as activated carbon, is highly effective at preventing migration of the enzyme, but can reduce mobility of the enzyme resulting in minimized or lost enzymatic activity. Alternatively, a substrate that weakly binds the urease preserves the catalytic activity, but may allow migration to occur if components present in the dialysate weaken the urease to substrate bond. Aluminum oxide is commonly used as a substrate for urease in sorbent dialysis because it provides a favorable combination of binding strength and retained activity. Urease that is physically bound to aluminum oxide can migrate when proteins and certain metal ions are present in the dialysate. If urease migrates into downstream layers in the sorbent cartridge the activity may be lost, leading to reduced functionality.

[0017] In certain types of substrates, urease is present in a non-woven pad coated with a urease solution. For example, a urease solution may be dispensed onto a non-woven polyester pad during cartridge manufacturing. The urease solution dries out inside the cartridge, leaving a urease coated polyester pad. During startup of the sorbent dialysis treatment, the cartridge is partially filled with water to dissolve the urease and allow it to bond onto an aluminum oxide substrate that is immediately downstream of the urease pad. In other sorbent systems, urease solution is applied to aluminum oxide and allowed to dry, then a mixture of coated and uncoated aluminum oxide is placed into the cartridge during manufacturing. In such substrates, the urease solution may require a relatively large amountDocket No.: MZM00005 PCT / 1246-069W001of urease (e.g., over three times a theoretical amount of urease needed for removing urea). In such types of substrates, the urease may tend to be removed or lost from the substrates over time, for example, by flow of fluid. Such a loss reduces the urea-removal capacity of the sorbent cartridge over time. Changes to urease function may impact rechargeability of sorbent cartridges.

[0018] In some examples according to the present disclosure, an example sorbent cartridge is configured to hydrolyze urea in a dialysate. The sorbent cartridge may include a substrate. In some examples, the substrate may include a mesh. The sorbent cartridge may further include a urea hydrolyzing species covalently linked to the substrate (for example, to the mesh).

[0019] The covalent linking of the urea hydrolyzing species to the substrate may immobilize the urea hydrolyzing species to the substrate, and promote the retention of the urea hydrolyzing species within the sorbent cartridge even in the presence of flowing fluid. Using a substrate including a mesh may permit flow of dialysate through the sorbent cartridge without a substantial obstruction to flow, while promoting contact between the dialysate and the urea hydrolyzing species, resulting in removal of urea from the dialysate by hydrolysis of the urea (e.g., into ammonia).

[0020] Any suitable surface attachment chemistry can be leveraged to immobilize a urea hydrolyzing species (e.g., an enzyme or a functional group) on a substrate. Such attachment may promote efficiency of the surface interaction (e.g., by using relatively less amounts of urea hydrolyzing species to achieve required function compared to non-immobilized urea hydrolyzing species), prevent migration of the urea hydrolyzing species during treatment, and may permit cartridge recharge for reuse after the sorbent cartridge is exhausted.

[0021] In some examples, a spacer molecule is used between the substrate and the urea hydrolyzing species. The spacer molecule is configured to allow the urea hydrolyzing species to be covalently attached to the substrate while also allowing mobility that increases enzymatic activity. For example, hydrophilic molecules such and poly(ethylene glycol) or polyacrylamide may be used, but any suitable linking molecule can be used. In some examples, the linkers may be hydrophilic, and provide sufficient spacing between the urea hydrolyzing species and the substrate to promote enzymatic activity, and may have functional groups that enable covalent attachment to the substrate and urea hydrolyzing species.

[0022] In some examples, a woven or non-woven mesh (e.g., including a polymer) may be used in a substrate, and the urea hydrolyzing species may be covalently attached to the mesh (e.g., to a filament, fiber, or a surface of the mesh). In some examples, the mesh mayDocket No.: MZM00005 PCT / 1246-069W001be treated (e.g., by plasma treatment or some other surface modification) prior to covalently attaching the urea hydrolyzing species. Any suitable covalent link may be formed, for example, a direct covalent link or an indirect coupling link. For example, the coupling link may include a coupling species bonded to the urea hydrolyzing species at one end and to the mesh at another end. In some examples, the coupling link may include a l-Ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride (EDC) / N-hydroxysuccinimide (NHS) link.

[0023] The mesh may be oriented along a mesh axis, and the mesh may be stacked in any predetermined arrangement of the mesh axis. For example, the mesh axis of neighboring mesh layers may be offset from each other. For example, offsetting mesh layers may provide a tortuous path, similar to that in a non-woven mesh, pad, or substrate. The mesh may include any suitable material. In some examples, the mesh includes at least one polymer. For example, the polymer may be substantially inert to the dialysate, and may not interfere with the flow of dialysate while permitting the dialysate to interact with the urea hydrolyzing species for removal of urea from the dialysate.

[0024] In some examples, a urease-impregnated or urease-coated pad may be replaced with a number of mesh layers, for example, a stack of 2, 3, 4, 5, or more mesh layers. Thus, the mesh layers may be used to replace non-immobilized urease substrates while remaining compatible with other layers that may be present in the sorbent cartridge and otherwise with the geometry and configuration of the sorbent cartridge. In some examples, the mesh layers may include an alternating pattern of offsets. Such immobilization and / or offset may reduce or prevent migration of urease during treatment and promote efficiency of the urease (or of any other urea hydrolyzing species).

[0025] In some examples, substrates according to the present disclosure may be incorporated in a secondary cartridge or filter used inline with another sorbent cartridge, instead of within a sorbent cartridge including other layers that remove other waste (e.g., other than urea). For example, such a configuration may permit recharging the sorbent cartridges, by separating urea removal to the secondary cartridge. The opening size of the meshes may be selected to be relatively small, for example, to replace or augment chemistry sensitive components in sorbent cartridges.

[0026] By covalently attaching the urea hydrolyzing species to a mesh, both the efficiency of urea hydrolysis and system function as a whole may be promoted. For example, a relatively lower amount of urease may be needed, by prevention of migration and known exposure (more consistent distribution across the mesh), allowing potential rechargeability ofDocket No.: MZM00005 PCT / 1246-069W001sorbent cartridges, and an opportunity to separate urea removal from the sorbent cartridge to a different component.

[0027] FIG. 1 A is a conceptual diagram illustrating a dialysis system 10 including a dialyzer 12 fluidly coupled to a sorbent cartridge 14 configured to hydrolyze urea in dialysate from dialyzer 12. Sorbent cartridge 14 includes a substrate 16. In some examples, substrate 16 includes a mesh 18.

[0028] FIG. IB is a conceptual diagram illustrating a partial side view of substrate 16 and a urea hydrolyzing species 20 covalently linked to substrate 16. Substrate 16 is configured to hydrolyze urea from the dialysate. In particular, urea hydrolyzing species 20 is configured to hydrolyze urea into ammonia. Urea hydrolyzing species 20 may include any suitable compound, functional group and / or enzyme capable of reducing (hydrolyzing) urea. In some examples, urea hydrolyzing species 20 includes a urease. In some examples, urea hydrolyzing species 20 consists of urease. Urea hydrolyzing species 20 may catalyze a reaction of urea to form ammonia and carbon dioxide, which in turn may form ammonium carbonate.

[0029] Urea hydrolyzing species 20 is immobilized to substrate 16 by a link 22. Link 22 may include one or more of an ionic bond, a linker that provides sufficiently strong secondary bonds to substrate 16 to prevent migration of urea hydrolyzing species 20, or a direct covalent bond (a covalent link) between urea hydrolyzing species 20 and substrate 16 (e.g., to mesh 18), or any combination of bonds. For example, a site (e.g., a linkage site) of urea hydrolyzing species 20 may be liked by the direct covalent bond to a corresponding site of substrate 16. The linkage site may include any suitable atom, ion, or functional group. In some examples, the linkage site of urea hydrolyzing species 20 includes a thiol or an amino group. The linkage site may include any suitable atom, ion, or functional group. In some examples, the linkage site includes a hydroxyl group. In some examples, one, two or more linkage sites are linked to one, two, or more linkage sites of urea hydrolyzing species 20. Thus, one, two, or more covalent links 22 may be present between substrate 16 and urea hydrolyzing species 20.

[0030] In some examples, link 22 includes at least one linking species. For example, urea hydrolyzing species 20 may be bonded to a first end of the at least one linking species, and substrate 16 may be bonded to a second end of the at least one linking species. In some examples, urea hydrolyzing species 20 may be bonded to the first end of the at least one linking species by a covalent bond. Likewise, substrate 16 may be bonded to the second end of the at least one linking species by a covalent bond.Docket No.: MZM00005 PCT / 1246-069W001

[0031] The linking species may include any suitable species. For example, the linking species may include a carbodiimide linkage or an acrylate linkage. In some examples, the linking species includes a l-ethyl-3 -(-3 -dimethylaminopropyl) carbodiimide hydrochloride (EDC) / A-hydroxysuccinimide (NHS) linkage. The NHS may be sulfonated (e.g., sulfo-NHS). In some examples, the linking species may include a streptavidin-biotin linkage, or a 4-(4,6-dimethoxy-l,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMTMM) linkage. In some examples, the linking species includes at least one radical, such that link 22 includes a radical-mediated link.

[0032] Any suitable areal density (count per unit area) for urea hydrolyzing species 20 and / or link 22 may be used along substrate 16 (e.g., along mesh 18). For example, an areal density of urea hydrolyzing species 20 may be the same or less than that of link 22. Thus, all or less than all links 22 may be coupled to corresponding urea hydrolyzing species 20. In some examples, substrate 16 may be initially treated or processed to provide a plurality of links 22, and some or all of links 22 may be coupled to urea hydrolyzing species 20. In other examples, individual links 22 may be initially coupled to urea hydrolyzing species 20 (e.g., in a solution), and substrate 16 may be treated with the solution to link urea hydrolyzing species 20 to substrate 16 via respective links 22.

[0033] In some examples, substrate 16 may be surface treated (e.g., plasma treated) to promote formation of link 22. In some examples, substrate 16 may be surface treated to promote formation of hydroxyl groups on substrate 16, prior to linking urea hydrolyzing species 20. For example, the hydroxyl groups may promote the immobilization of urea hydrolyzing species 20 by forming links 22 coupled to the hydroxyl groups.

[0034] Substrate 16 (e.g., mesh 18 or another portion, component, or form of substrate 16) may include any suitable material capable of linking urea hydrolyzing species 20 via link 22. In some examples, substrate 16 includes one or more of a metal, an alloy, a glass, a ceramic, or a polymer. In some examples, substrate 16 (e.g., mesh 18) includes, consists of, or consists essentially of at least one polymer. The polymer may include one or more of a polyolefin, a polyester, a polysulfone, a polyethersulfone, a polyamide, a polyurethane, a poly(methacrylate), a poly(acrylate), a cellulose, or a fluoropolymer, or blends or copolymers thereof. In some examples, substrate 16 includes woven plasma treated meshes in a ranges of 80 / 20 to 350 / 44. In some such examples, substrate 16 includes a polypropylene and / or a polyethersulfone.Docket No.: MZM00005 PCT / 1246-069W001

[0035] Mesh 18 (or substrate 16) may be dry before contact with dialysate. For example, substrate 16 may be manufactured and introduced into sorbent cartridge 14 as a dry component prior to use.

[0036] Mesh 18 may include one or more of filaments (e.g., individual strands or monofilament), fibers (combined or wound strands), bundles (aggregates of filaments and / or fibers). The filaments, fibers, or bundles may include a homogenous composition (e.g., each having an identical composition) or a heterogeneous composition. Further, mesh 18 may include a heterogeneous distribution of homogeneous filaments, fibers, orbundies (e.g., two or more types of filaments, fibers, or bundles). Mesh 18 may include a woven or non-woven mesh body.

[0037] System 10 may further include a pump 34 configured to recirculate dialysate from dialyzer 12 to sorbent cartridge 14. Pump 34 may include any suitable type of pump configured to recirculate a fluid (e.g., dialysate) in system 10.

[0038] FIG. 2 is a conceptual diagram illustrating a mesh layer 118 including a woven mesh body 119. Mesh layer 118 along with woven mesh body 119 form an example of mesh 18. Mesh layer 118 may be generally similar in composition to mesh 18, other than the differences described with reference to FIG. 2. Woven mesh body 119 may include a warp and a weft having any suitable predetermined widths (along a plane of mesh body 119) and thicknesses (across the plane of mesh body 119), and defining any suitable opening sizes or % opening area between the warp and the weft. The warp and / or the weft may include monofilaments, two or more filaments, fibers, or bundles. The warp and / or the weft may be regular (e.g., extending along straight lines) or irregular (e.g., extending along paths that deviate from a straight line).

[0039] FIG. 3 is a conceptual diagram illustrating a mesh layer 218 including a nonwoven mesh body 219. Mesh layer 218 along with woven mesh body 219 form an example of mesh 18. Mesh layer 218 may be generally similar in composition to mesh 18, other than the differences described with reference to FIG. 3. Non-woven mesh body 219 may include one or more of monofilaments, two or more filaments, fibers, or bundles. In some examples, non-woven mesh body 219 includes, consists of, or consists essentially of monofilaments. Non-woven mesh body 219 may include filaments, fibers, or bundles having any suitable predetermined widths (along a plane of mesh body 219) and thicknesses (across the plane of mesh body 219), and defining any suitable average and / or maximum opening sizes (e.g., average opening area) between the warp and the weft.Docket No.: MZM00005 PCT / 1246-069W001

[0040] Woven mesh body 119 or non-woven mesh body 219 may have an opening area of at least 10%, at least 20%, at least 30%, at least 40%, or at least 50%. Woven mesh body 119 or non-woven mesh body 219 may have an opening area of 60% or less, 50% or less, 40% or less, 30% or less, 20% or less, or 10% or less. For example, woven mesh body 119 or non-woven mesh body 219 may have an average or maximum mesh opening size of at least 10pm, at least 20pm, at least 50pm, at least 100pm, at least 150pm, at least 200 pm, or at least 300 pm. Woven mesh body 119 or non-woven mesh body 219 may have an average or maximum mesh opening size of 60% or less, 50% or less, 40% or less, 30% or less, 20% or less, or 10% or less.

[0041] Woven mesh body 119 or non-woven mesh body 219 may have any suitable areal weight. For example, the areal weight may be at least 10 g / m2, at least 20 g / m2, at least 30 g / m2, at least 50 g / m2, at least 100 g / m2, or at least 120 g / m2. The areal weight may be less than or equal to 150 g / m2, less than or equal to 100 g / m2, less than or equal to 50 g / m2, less than or equal to 30 g / m2, less than or equal to 20 g / m2, or less than or equal to 10 g / m2.Woven mesh body 119 or non-woven mesh body 219 may have any suitable mesh. For example, the mesh count may be at least 20 count / cm, at least 40 count / cm, at least 60 count / cm, at least 80 count / cm, at least 100 count / cm, at least 150 count / cm, or at least 200 count / cm. The mesh may be less than or equal to 250 count / cm, less than or equal to 200 count / cm, less than or equal to 150 count / cm, less than or equal to 100 count / cm, less than or equal to 80 count / cm, less than or equal to 60 count / cm, or less than or equal to 40 count / cm.

[0042] FIG. 4 is a conceptual diagram illustrating a mesh 318 comprising a plurality of mesh layers 319. Mesh 318 along with plurality of mesh layers 319 form an example of mesh 18. One layer, more than one layer, or all layers of mesh layers 319 may include woven mesh body 119 or non-woven mesh body 219. In some examples, each layer of plurality of mesh layers 319 includes or consists of woven mesh body 119. In some examples, each layer of plurality of mesh layers 319 includes or consists of non-woven mesh body 219.

[0043] In mesh 318, urea-hydrolyzing species 20 is covalently linked to at least one mesh layer of plurality of mesh layers 319. In some examples, urea-hydrolyzing species 20 is covalently linked to each mesh layer of plurality of mesh layers 319. In other examples, urea-hydrolyzing species 20 is covalently linked to less than all mesh layers of plurality of mesh layers 319, for example, to alternating layers, or every third layer, or every fourth layer, or some other random or predetermined pattern of layers.Docket No.: MZM00005 PCT / 1246-069W001

[0044] Each mesh layer of plurality of mesh layers 319 may be oriented along a respective axis. For example, the respective axis may be aligned with a direction of maximum opening elongation, maximum fiber density, minimum opening elongation, or minimum fiber density. In some examples, the respective axis is along a warp direction or a weft direction.

[0045] In some examples, a first mesh layer 319A of plurality of mesh layers 319 is oriented along a first mesh axis Al, and a second mesh layer 319B of plurality of mesh layers 319 is oriented along a second mesh axis A2 laterally offset with respect to first mesh axis Al. The offset may be determined as an angle a between first mesh axis Al and second axis A2. In some examples, second mesh axis A2 is laterally offset with respect to first mesh axis Al in a range from 15 degrees to 90 degrees. In some examples, each successive mesh layer of plurality of mesh layers 319 is respectively offset from a neighboring mesh layer. In some examples, the offset between each pair of neighboring mesh layers is the same. For example, each pair of layers may be offset by an angle in a range from 15 degrees to 90 degrees (e.g., 15 degrees, 30 degrees, 45 degrees, 60 degrees, 75 degrees, or 90 degrees, or some other intervening angle). In other examples, the offset between pairs of neighboring mesh layers varies in a predetermined pattern. For example, the offset may alternate between alternating pairs.

[0046] Plurality of mesh layers 319 may define at least one tortuous path 321 for receiving urea through at least a portion of mesh 318. For example, openings of adjacent mesh layers of plurality of mesh layers 319 may together define a tortuous path 321. In some examples, a configuration (e.g., length, tortuosity, or width) of tortuous path 321 depends on the offset between adjacent mesh layers of plurality of mesh layers 319. Thus, the offset can be set to achieve a predetermined configuration for tortuous path 321. At least one tortuous path 321 may prolong the residence time of urea in mesh 318, thus promoting hydrolysis of urea by urea hydrolyzing species via an extended interaction time.

[0047] Turning back to system 10 of FIG. 1 A, mesh 18 of sorbent cartridge 14 may include any suitable mesh according to the present disclosure, for example, one or more of mesh 118, 218, or 318. In some examples, substrate 16 (or mesh 18) is the sole sorbent component in sorbent cartridge 14.

[0048] While substrate 16 of sorbent cartridge 14 includes mesh 18 configured to extract urea from a dialysate, in other examples, substrate 16 may include any suitable substrate body in addition to or instead of mesh 18. Thus, urea-hydrolyzing species 20 may be linked to any suitable substrate body of substrate 16. For example, the substrate body may include one orDocket No.: MZM00005 PCT / 1246-069W001more of mesh 18, a bead (e.g., solid or porous), particulates (e.g., coated particles), a mat, or a sheet. For example, the substrate body may be inert to dialysis fluid and have a relatively high surface area to allow sufficient binding of the urea hydrolyzing species work. In some examples, the substrate body includes coated particles of activated alumina, activated carbon, silica, crosslinked polyacrylamide or other materials. In some examples, the substrate body includes a dry substrate body having any suitable shape or form.

[0049] Sorbent cartridge 14 may contain any suitable number or types of substrate 16 (e.g., one, two or more substrates that are identical, similar, or different in one or more of shape, size, or composition). Further, sorbent cartridge 14 may optionally include additional layers configured to extract other types of waste or contaminants from the dialysate.

[0050] For example, sorbent cartridge 14 may optionally further include one or more of an activated carbon layer 24, an alumina layer 26, a zirconium oxide layer 28, or a zirconium phosphate layer 30. Activated carbon layer 24 may be configured to remove nonionic toxins from the dialysate by adsorption. For example, one or more of creatinine, glucose, uric acid, P2-microglobulin or other non-ionic toxins (e.g., other than urea), may be adsorbed onto activated carbon in activated carbon layer 24, removing those toxins from the dialysate. Other non-ionic toxins may also be removed by the activated carbon. Zirconium oxide layer 28 may be configured to remove phosphate and fluoride anions, exchanging them for acetate anions. Phosphate anions present in the dialysate may also be exchanged for hydroxide ions in alumina layer 26. Alumina layer 26 may remove remaining phosphate ions from the dialysate. Zirconium phosphate layer 30 may be configured to exchange ammonium, calcium, potassium and magnesium cations for sodium and hydrogen cations. Ammonium, calcium, potassium and magnesium ions all preferentially bind to the zirconium phosphate, releasing the hydrogen and sodium ions originally present in the layer. The ratio of sodium to hydrogen ions released depends on the ratio originally present in the zirconium phosphate layer 30, and is therefore controllable.

[0051] In some examples, substrate 16 is between activated carbon layer 24 and zirconium phosphate layer 30. While a particular arrangement of substrate 16 relative to various layers is shown in FIG. 1 A, any other suitable arrangement may be used. Further, substrate 16 or other layers of sorbent cartridge 14 may be generally disk-shaped, or have any other suitable shape or configuration. Sorbent cartridge 14 may further include a cartridge housing 32 configured to retain substrate 16 and / or other layers of sorbent cartridge 14. Cartridge housing 32 may be cylindrical, or have any other suitable shape.Docket No.: MZM00005 PCT / 1246-069W001

[0052] FIG. 5 is a flow diagram illustrating an example technique for forming sorbent cartridge 14. While the example technique of FIG. 5 is described with reference to sorbent cartridge 14 of FIG. 1 A, the example technique may be used to prepare any other sorbent cartridge (or substrate) according to the present disclosure, and sorbent cartridge 14 may be formed using any suitable technique.

[0053] In some examples, the technique includes covalently linking urea hydrolyzing species 20 to substrate 16 of sorbent cartridge 14 (402). For example, the covalently linking may include forming link 22 between urea hydrolyzing species 20 and substrate 16 (e.g., with mesh 18). In some examples, a plurality of links 22 may be deposited on mesh 18, and a composition (e.g., a solution, a mixture, or a dispersion) including urea hydrolyzing species 20 may be contacted with mesh 18 to cause urea hydrolyzing species 20 to attach to links 22. In other examples, urea hydrolyzing species 20 may include a functional group that forms link 22 with mesh 18 when contacted with mesh 18. In examples, in which mesh 18 includes a plurality of mesh layers, and the technique may include covalently linking urea-hydrolyzing species 20 to at least one mesh layer (one, more than one, less than all, or all) of the plurality of mesh layers.

[0054] In some examples, a mesh precursor (example, a web, a roll, a sheet or some other precursor or bulk form of a mesh) is treated to link urea-hydrolyzing species 20 via links 22, and then the mesh precursor may be cut or machined to form shaped mesh 18 (e.g., as disks). In other examples, the mesh precursor is initially cut or machined to form shaped mesh 18 (e.g., as disks), and then shaped mesh 18 is treated to link urea-hydrolyzing species 20 via links 22.

[0055] In some examples, the technique further includes orienting a first mesh layer of the plurality of mesh layers (e.g., first mesh 319A) along first mesh axis Al and orienting a second mesh layer of the plurality of mesh layers (e.g., second mesh 319B) along a second mesh axis A2 laterally offset with respect to first mesh axis Al. In some examples, urea hydrolyzing species 20 is covalently linked to mesh 18 of the substrate after orienting the first mesh layer and after orienting the second mesh layer. For example, the second mesh axis may be laterally offset with respect to the first mesh axis in a range from 15 degrees to 90 degrees.

[0056] In some examples, the technique further includes drying substrate 16 (e.g., after urea hydrolyzing species 20 is covalently linked to mesh 18). The drying may include forced drying, air drying, or passive drying at ambient temperature or pressure, or at elevated temperatures, or under vacuum.Docket No.: MZM00005 PCT / 1246-069W001

[0057] In some examples, the covalently linking 402 includes covalently linking urea hydrolyzing species 20 to mesh 18 of substrate 16 via l-ethyl-3 -(-3 -dimethylaminopropyl) carbodiimide hydrochloride (EDC) / N-hydroxysuccinimide (NHS) coupling.

[0058] The technique may further include introducing substrate 16 (including mesh 18 and urea hydrolyzing species 20) within housing 32 of sorbent cartridge 14 (406).

[0059] The technique may further include introducing one or more of activated carbon layer 24, alumina layer 26, zirconium oxide layer 28, or zirconium phosphate layer 30 within housing 32 of sorbent cartridge 14 (408).

[0060] While articles, systems, and techniques according to the present disclosure may be used for hemodialysis, they may also be used for any other dialysis applications.

[0061] It should be understood that various aspects disclosed herein may be combined in different combinations than the combinations specifically presented in the description and accompanying drawings. It should also be understood that, depending on the example, certain acts or events of any of the processes or methods described herein may be performed in a different sequence, may be added, merged, or left out altogether (e.g., all described acts or events may not be necessary to carry out the techniques).

[0062] The above detailed descriptions of examples of the technology are not intended to be exhaustive or to limit the technology to the precise form disclosed above. Although specific examples of the technology are described above for illustrative purposes, various equivalent modifications are possible within the scope of the technology, as those skilled in the relevant art will recognize. For example, while steps are presented in a given order, alternative examples may perform steps in a different order. The various examples described herein may also be combined to provide further examples. All references cited herein are incorporated by reference as if fully set forth herein.

[0063] Various examples have been described. These and other examples are within the scope of the following claims.

Claims

Docket No.: MZM00005 PCT / 1246-069W001WHAT IS CLAIMED IS:

1. A sorbent cartridge configured to hydrolyze urea in a dialysate, the sorbent cartridge comprising:a substrate comprising a mesh; anda urea hydrolyzing species covalently linked to the mesh of the substrate.

2. The sorbent cartridge of claim 1, wherein the mesh comprises a plurality of mesh layers, wherein the urea-hydrolyzing species is covalently linked to at least one mesh layer of the plurality of mesh layers.

3. The sorbent cartridge of claim 2, wherein a first mesh layer of the plurality of mesh layers is oriented along a first mesh axis, wherein a second mesh layer of the plurality of mesh layers is oriented along a second mesh axis laterally offset with respect to the first mesh axis.

4. The sorbent cartridge of claim 3, wherein the second mesh axis is laterally offset with respect to the first mesh axis in a range from 15 degrees to 90 degrees.

5. The sorbent cartridge of any one of claims 2 to 4, wherein the plurality of mesh layers defines a tortuous path for receiving urea through at least a portion of the mesh.

6. The sorbent cartridge of any one of claims 1 to 5, wherein the mesh comprises a woven mesh body.

7. The sorbent cartridge of any one of claims 1 to 6, wherein the mesh comprises a nonwoven mesh body.

8. The sorbent cartridge of any one of claims 1 to 7, wherein the mesh comprises a polymer.

9. The sorbent cartridge of claim 8, wherein the polymer comprises one or more of a polyolefin, a polyester, a polysulfone, a polyethersulfone, a polyamide, a polyurethane, a poly(methacrylate), a poly(acrylate), a cellulose, or a fluoropolymer.Docket No.: MZM00005 PCT / 1246-069W00110. The sorbent cartridge of any one of claims 1 to 9, wherein the urea hydrolyzing species comprises a urease.

11. The sorbent cartridge of any one of claims 1 to 10, wherein the urea hydrolyzing species is covalently linked to the mesh of the substrate via l-ethyl-3-(-3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) / 7V-hydroxysuccinimide (NHS) coupling.

12. The sorbent cartridge of any one of claims 1 to 11, wherein the sorbent cartridge further comprises one or more of an activated carbon layer, an alumina layer, a zirconium oxide layer, or a zirconium phosphate layer.

13. The sorbent cartridge of claim 12, wherein the sorbent cartridge comprises an activated carbon layer and a zirconium phosphate layer, and wherein the substrate is between the activated carbon layer and the zirconium phosphate layer.

14. The sorbent cartridge of any one of claims 1 to 11, wherein the substrate is dry.

15. A method comprising forming the sorbent cartridge of any one of claims 1 to 14.

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