Liquid pumping cartridge and associated pressure distribution manifold and related methods

Abstract

A fluid handling cartridge (80) includes at least one of a fluid actuated diaphragm valve (82) and a fluid actuated diaphragm pump (84), with actuation fluid supplied to the cartridge (80) through an actuation port (96) located along a thin or narrow edge of the cartridge (80). An actuation channel (110) within the cartridge leads from the actuation port (96) to an actuation chamber of the valve and pump in a space between plates (86, 90, 88) making up the cartridge (80). Each plate (86, 90, 88) has a nominal thickness sufficient to provide a rigid ceiling for the actuation channel (110), but thin enough to minimize the overall thickness of the cartridge. Multiple such cartridges (80) can be stacked together or spaced apart from one another to form a cartridge assembly, providing a convenient way to install and remove the cartridge assembly from an actuation receptacle of the cartridge assembly. This arrangement allows for an improved way of connecting a complex cartridge assembly to an associated pressure distribution manifold of the cartridge assembly without the need for multiple flexible connection tubes between the cartridge assembly and the associated pressure distribution manifold of the cartridge assembly.

Description

[0001] This application is a divisional of the application patent application with the application date of 2019-03-29, the application number of 201980034132.7 (PCT / US2019 / 024933), and the invention name of "Liquid Pumping Cartridge and Associated Pressure Distribution Manifold and Related Methods". TECHNICAL FIELD

[0002] The present disclosure relates generally to improvements in the design and construction of fluid pumping or mixing cartridges, cartridge assemblies, their constituent components, and associated equipment. BACKGROUND

[0003] Liquid handling cartridges that include diaphragm pumps and / or diaphragm valves can be fluidically (hydraulically or pneumatically) actuated. In some examples, the cartridges are designed to be fluidically connected to a pneumatically actuated manifold having electromechanical valves that selectively distribute positive or negative pressurized gas or air to the cartridges. Programmable electronic controllers can be used to control the electromechanical valves in order to selectively deliver positive pneumatic pressure or negative pneumatic pressure to various pumps or valves of the cartridges in a predetermined manner.

[0004] The shape of some fluid handling cartridges can be generally flat, with a wide side having two sides that are thin or narrow sides having a relatively small thickness compared to the overall wide side dimension of the cartridge. Liquid inlet and outlet ports can be included into the edges or thin sides of the cartridge. However, in many such devices, the actuation ports for the cartridges are located on the face or wide side of the cartridge directly above the actuation chambers of the pumps or valves being controlled. This generally provides the shortest route for the actuation channels in the cartridge from the external cartridge actuation ports to the actuation chambers and diaphragms of the pumps or valves in the cartridge. Furthermore, in many cases, the pump stations or valve stations or regions of the cartridge that include actuation chambers on one side or carry liquid chambers on the opposite side can be defined by spherical or hemispherical chamber walls that extend above the plane of the face of the cartridge, which makes the overall thickness of the cartridge thicker than the cartridge thickness that is desired in some applications. In other cases, the pump modules can include a set of blocks that are sandwiched together or laminated together, with pneumatic actuation channels or fluid channels embedded within one or more of the blocks. Such arrangements can also result in an overall thickness of the device that is greater than the desired thickness for certain applications. Some applications can require multiple fluid handling cartridges to be mounted in close proximity to one another in a compact space. In these cases, it can be desirable to position multiple cartridges adjacent to one another so that the multiple cartridges are stacked against one another, or at least so that the wide sides of the multiple cartridges are placed face-to-face in close proximity. It can be particularly desirable to reduce or minimize the thickness of the individual cartridges that make up these assemblies.

[0005] It can be advantageous to arrange the pump cassette to plug directly into a pressure distribution manifold associated with the pump cassette (e.g., a manifold that selectively delivers pneumatic pressure to the pump cassette under the control of an electronic controller). In previously disclosed embodiments of a hemodialysis system using pneumatically actuated self-contained pump cassettes, the pump cassettes are connected to corresponding pneumatic manifolds via flexible tubing, which presents significant challenges during assembly and in the operation of the pump cassettes. A direct plug-in connection between the pump cassette and the associated manifold would have significant advantages if the pump cassette could be positioned in close proximity to the associated manifold of the pump cassette. In these cases, it would be particularly advantageous to have a compact manifold that allows direct interfacing with the pump cassette, arranged to allow plugging or unplugging of the cassette or cassette assembly into or from the actuation ports of the manifold with minimal force.

[0006] The ability to use binary pressure control valves instead of valves with continuously variable orifices would also provide significant advantages in both cost and reliability in the design and operation of a pneumatic distribution manifold. But in this case, the control of pressure delivery to individual cassette pumps or cassette valves by binary pressure control valves presents additional challenges that must be overcome. A sufficiently stable electronic controller can be programmed to use control algorithms to control the frequency and duration of binary valve actuation to achieve precise control of the associated pneumatically actuated pump or valve. SUMMARY

[0007] In embodiments, the pump and / or valve cassette has a relatively flat shape, with a wide side having narrow sides or edges that are relatively thin on both sides. The pump and / or valve cassette includes a middle plate positioned between two outer plates: a first outer plate facing a first side of the middle plate and a second outer plate facing an opposite second side of the middle plate. The first outer plate is spaced apart from the middle plate to form a first inter-plate space. The second outer plate is spaced apart from the middle plate to form a second inter-plate space. The thickness of the first and second outer plates is limited to a thickness sufficient to impart rigidity to the plates and provide a sealing surface against an opposite channel wall of either side of the middle plate. In some embodiments, the thickness of each outer plate, together with the thickness of the middle plate between the outer plates, defines the overall thickness of the cassette. In other embodiments, the liquid inlet and outlet ports extend from the outside of the cassette, which adds to the overall thickness of the cassette. The cassette can include one or more pump stations or regions and two or more valve stations or regions. The number of pump or valve stations and the size of the pump or valve stations can determine the overall wide side dimension of the cassette. The stroke volume of the on-board pump is a function of the diameter of the pump station and its associated diaphragm and the offset depth of the diaphragm defined by the depth of the channel wall of the middle plate, which in turn will determine the thickness of the cassette and the wide side dimension of the cassette. For any given pump or valve station, the middle plate includes an actuation side and an opposite liquid side, with the actuation side holding the pump diaphragm or valve diaphragm. The actuation channel in the cassette leading to the respective pump or valve station can be included within the middle plate channel of the first inter-plate space and extends generally parallel to the wide side of the cassette. The liquid channel in the cassette can be included within the middle plate channel of the second inter-plate space and also extends generally parallel to the wide side of the cassette, unless in some cases the liquid channel connects to the inlet or outlet of the cassette. In this arrangement, the first and second outer plates are primarily used to provide a top plate or confinement wall over the respective actuation valve or pump region and the liquid carrying valve or pump region.

[0008] In an embodiment, a fluidic processing cartridge can include an intermediate plate positioned between a first plate and a second plate, the plates having a length, a width, and a plate thickness, a first side of the intermediate plate opposing the first plate and a second side of the intermediate plate opposing the second plate. The first plate is spaced apart from the intermediate plate defining a width of a first inter-plate space, and the second plate is spaced apart from the intermediate plate defining a width of a second inter-plate space. An edge of the cartridge has a cartridge thickness defined by the thickness of each plate plus the width of the first inter-plate space and the width of the second inter-plate space, and a face of the cartridge is defined by the length and width of the first plate or the length and width of the second plate. The intermediate plate can include a pump station defined by a pump diaphragm seated against the first side of the intermediate plate and having an offset range defined by the width of the first inter-plate space. A pump actuation channel extends in the first inter-plate space parallel to the face of the cartridge connecting a pump actuation chamber defined by the first plate and the pump diaphragm with a cartridge pump actuation port located within the first inter-plate space and at a first edge of the cartridge. A first pump fluid port and a second pump fluid port in the pump station can fluidically connect respective first and second fluid channels in the second inter-plate space to a pumping chamber defined by the pump diaphragm and the first side of the intermediate plate. The pump fluid ports in the pump station can fluidically connect a fluid channel in the second inter-plate space with a pumping chamber defined by the pump diaphragm and the first side of the intermediate plate. Alternatively, an orifice can be provided in the intermediate plate at the pump station that allows the pump diaphragm to move from the first plate to the second plate upon actuation by positive or negative pressure delivered through the pump actuation channel. The thickness of the plates (first plate, intermediate plate, and second plate) is generally insufficient to allow a fluid channel or actuation channel to travel within the plate in a direction parallel to the face of the cartridge. The fluid channel can extend in the second inter-plate space and fluidically connect to the pumping chamber defined by the pump diaphragm and the first side of the intermediate plate through one or more pump fluid ports in the intermediate plate such that the fluid channel extends in the second inter-plate space parallel to the face of the cartridge connecting the pumping chamber with a cartridge fluid port located within the second inter-plate space and at a first or second edge of the cartridge.

[0009] In an embodiment, a fluidic processing cartridge can include an intermediate plate positioned between a first plate and a second plate, the plates having a length, a width, and a plate thickness, a first side of the intermediate plate opposing the first plate and a second side of the intermediate plate opposing the second plate. The first plate is spaced apart from the intermediate plate to define a width of a first inter-plate space, and the second plate is spaced apart from the intermediate plate to define a width of a second inter-plate space. An edge of the cartridge has a cartridge thickness defined by the thickness of each plate plus the width of the first inter-plate space and the width of the second inter-plate space, and a face of the cartridge is defined by the length and width of the first plate or the length and width of the second plate. The intermediate plate can include a valve station defined by a valve septum and the first side of the intermediate plate, the valve septum seated against the first side of the intermediate plate and having an offset range defined by the width of the first inter-plate space. And a valve actuation channel can extend in the first inter-plate space parallel to the face of the cartridge to connect a valve actuation chamber defined by the first plate and the valve septum to a cartridge valve actuation port located within the first inter-plate space and at the first edge of the cartridge. A first valve fluid port and a second valve fluid port in the valve station can fluidically connect respective first and second fluid channels in the second inter-plate space to a valve fluid chamber defined by the valve septum and the first side of the intermediate plate. One or both valve fluid ports can include a raised valve seat to seal the valve septum over the first or second valve fluid port upon application of positive pressure to the valve septum via the valve actuation channel. The first fluid channel and the second fluid channel are fluidically isolated except through the first and second valve fluid ports. The fluid channels can extend in the second inter-plate space and are fluidically connected to the valve fluid chamber defined by the valve septum and the first side of the intermediate plate through the two valve fluid ports in the intermediate plate such that the fluid channels extend in the second inter-plate space parallel to the face of the cartridge to connect the valve fluid chamber to a cartridge fluid port located within the second inter-plate space and at the first or second edge of the cartridge.

[0010] In another embodiment, a fluid handling cartridge can include an intermediate plate positioned between a first plate and a second plate, the plates having a length, a width, and a plate thickness, a first side of the intermediate plate opposing the first plate and a second side of the intermediate plate opposing the second plate. The first plate is spaced apart from the intermediate plate defining a first inter-plate space width and the second plate is spaced apart from the intermediate plate defining a second inter-plate space width. An edge of the cartridge has a cartridge thickness defined by the thickness of each plate plus the first inter-plate space width and the second inter-plate space width and a face of the cartridge is defined by the length and width of the first plate or the length and width of the second plate. The intermediate plate can include a pump station defined by a pump diaphragm seated against the first side of the intermediate plate and having an offset range defined by the first inter-plate space width. The intermediate plate can also include a first valve station and a second valve station, each valve station defined by a valve diaphragm seated against the first side of the intermediate plate and having an offset range defined by the first inter-plate space width. Pump actuation channels for the pump station and valve actuation channels for each of the first and second valve stations are provided. The pump actuation channels extend in the first inter-plate space parallel to the face of the cartridge connecting a pump actuation chamber defined by the first plate and the pump diaphragm with a cartridge pump actuation port located within the first inter-plate space at the first edge of the cartridge. And each of the valve actuation channels extends in the first inter-plate space parallel to the face of the cartridge connecting a valve actuation chamber defined by the first plate and the valve diaphragm with a cartridge valve actuation port located within the first inter-plate space at the first edge of the cartridge. An inlet valve fluid port and an outlet valve fluid port can be provided in each of the two valve stations and one or more pump fluid ports in the pump station, each of the valve and pump fluid ports fluidically connecting a fluid channel in the second inter-plate space with: a pumping chamber defined by the pump diaphragm and the first side of the intermediate plate; and a valve fluid chamber in each of the valve stations defined by the corresponding valve diaphragm and the first side of the intermediate plate. The fluid channel has a flow path through the inlet and outlet valve fluid ports and the one or more pump fluid ports such that selective actuation of the pump and valve actuation chambers allows unidirectional flow of fluid through the fluid channel. The fluid channel can extend in the second inter-plate space and fluidically connect to: the pumping chamber defined by the pump diaphragm and the first side of the intermediate plate through a pump fluid port in the intermediate plate; and the valve fluid chamber of each valve station, each of the valve fluid chambers defined by the corresponding valve diaphragm and the first side of the intermediate plate through two valve fluid ports in the intermediate plate, such that the fluid channel extends in the second inter-plate space parallel to the face of the cartridge connecting the pumping chamber and each of the valve fluid chambers with a cartridge fluid inlet port and a cartridge fluid outlet port located within the second inter-plate space at the first or second edge of the cartridge.The cartridge fluid inlet port and the cartridge fluid outlet port can be located at the second edge of the cartridge such that the cartridge pump actuation port and the cartridge valve actuation port are configured to plug directly into mating actuation receptacles on the exterior of the cartridge, and such that the fluid inlet port and the fluid outlet port are arranged to connect to a fluid source or destination on the exterior of the cartridge via a flexible or malleable tube. The fluid channel can extend in the second inter-plate space and fluidically connect to: a pumping chamber defined by the pump diaphragm and the first side of the intermediate plate, the connection being made through a pump fluid port in the intermediate plate; and a valve fluid chamber of each valve station, each of the valve fluid chambers being defined by a corresponding valve diaphragm and the first side of the intermediate plate, each of the connections being made through two valve fluid ports in the intermediate plate. The fluid channel can then extend in the second inter-plate space parallel to the face of the cartridge and connect the pumping chamber and each of the valve fluid chambers with the cartridge fluid inlet port and the cartridge fluid outlet port, the cartridge fluid inlet port and the cartridge fluid outlet port exiting the cartridge through rigid conduits that originate at the intermediate plate and penetrate the face of the cartridge through the first outer plate or the second outer plate.

[0011] In yet another implementation, a plurality of walls can be formed on the first side and the second side of the intermediate plate, the walls being arranged to be fusion bonded with the first plate and the second plate to form actuation channels or fluid channels within the cartridge. A first type of wall can include parallel walls to define an actuation channel or a fluid channel, a second type of wall can include a circumferential perimeter wall defining a pump actuation station or a valve actuation station, and a third type of wall can include an adjacent end wall defining a channel end at which a valve fluid port or a pump fluid port penetrates the intermediate plate. The first plate can include one or more circumferential valve diaphragm retainers or pump diaphragm retainers configured to fit within the circumferential perimeter wall of the opposing intermediate plate defining a pump actuation station or a valve actuation station, the retainers being arranged to clamp a peripheral edge or rim of an associated diaphragm positioned in the pump station or the valve station of the intermediate plate. The retainers can include a hole, a perforation, or a slot to allow actuation fluid or gas to pass between the valve actuation chamber or the pump actuation chamber surrounded by the retainers and the associated actuation channel. The first plate can include an elongated rib configured to be positioned within a mating actuation channel of the intermediate plate, the cross-sectional dimensions and length of the rib being arranged to regulate the actuation channel volume to a predetermined value between the actuation port of the cartridge and the associated valve actuation chamber or pump actuation chamber.

[0012] In another implementation, a fluid processing cartridge can include an intermediate plate positioned between a first plate and a second plate, the plates having a length, a width, and a plate thickness, a first side of the intermediate plate opposing the first plate and a second side of the intermediate plate opposing the second plate. The first plate is spaced apart from the intermediate plate to define a first inter-plate space width and the second plate is spaced apart from the intermediate plate to define a second inter-plate space width. An edge of the cartridge has a cartridge thickness defined by the thickness of each plate plus the first inter-plate space width and the second inter-plate space width, and a face of the cartridge is defined by the length and width of the first plate or the length and width of the second plate. The intermediate plate can include a first valve station defined by a first valve septum and the first side of the intermediate plate and a second valve station defined by a second valve septum and the second side of the intermediate plate, the first valve septum seated against the first side of the intermediate plate and having an offset range defined by the first inter-plate space width and the second valve septum seated against the second side of the intermediate plate and having an offset range defined by the second inter-plate space width. A first valve actuation channel for the first valve station can extend parallel to the face of the cartridge in the first inter-plate space and a second valve actuation channel for the second valve station can extend parallel to the face of the cartridge in the second inter-plate space. The first valve actuation channel connects a first valve actuation chamber defined by the first plate and the first valve septum to a first cartridge valve actuation port located within the first inter-plate space and at a first edge of the cartridge, and the second valve actuation channel connects a second valve actuation chamber defined by the second plate and the second valve septum to a second cartridge valve actuation port located within the second inter-plate space and at the first edge of the cartridge.

[0013] In another implementation, a fluid processing cartridge can include an intermediate plate positioned between a first plate and a second plate, the plates having a length, a width, and a plate thickness, a first side of the intermediate plate opposing the first plate and a second side of the intermediate plate opposing the second plate. The first plate is spaced apart from the intermediate plate to define a first inter-plate space width and the second plate is spaced apart from the intermediate plate to define a second inter-plate space width. An edge of the cartridge has a cartridge thickness defined by the thickness of each plate plus the first inter-plate space width and the second inter-plate space width, and a face of the cartridge is defined by the length and width of the first plate or the length and width of the second plate. The intermediate plate can include a first pump station defined by a first pump diaphragm and the first side of the intermediate plate and a second pump station defined by a second pump diaphragm and the second side of the intermediate plate, the first pump diaphragm seated against the first side of the intermediate plate and having an offset range defined by the first inter-plate space width and the second pump diaphragm seated against the second side of the intermediate plate and having an offset range defined by the second inter-plate space width. A first pump actuation channel for the first pump station can extend parallel to the face of the cartridge in the first inter-plate space, and a second pump actuation channel for the second pump station can extend parallel to the face of the cartridge in the second inter-plate space, the first pump actuation channel connecting a first pump actuation chamber defined by the first plate and the first pump diaphragm with a first cartridge pump actuation port located within the first inter-plate space and at a first edge of the cartridge. The second pump actuation channel connects a second pump actuation chamber defined by the second plate and the second pump diaphragm with a second cartridge pump actuation port located within the second inter-plate space and at the first edge of the cartridge.

[0014] In another embodiment, a fluid processing cassette assembly can include an intermediate cassette positioned between a first outer cassette and a second outer cassette, each cassette including an intermediate plate positioned between a first plate and a second plate, the plates having a length, a width, and a plate thickness, a first side of the intermediate plate opposing the first plate and a second side of the intermediate plate opposing the second plate. The first plate is spaced apart from the intermediate plate defining a first inter-plate space width, and the second plate is spaced apart from the intermediate plate defining a second inter-plate space width. An edge of the cassette has a cassette thickness defined by the thickness of each plate plus the first inter-plate space width and the second inter-plate space width, and a face of the cassette is defined by the length and width of the first plate or the length and width of the second plate. A plurality of diaphragm valves or diaphragm pumps including a valve actuation chamber or a pump actuation chamber can be connected to an actuation channel extending parallel to the face of the cassette within the first inter-plate space or the second inter-plate space and terminating at a respective cassette valve actuation port or cassette pump actuation port at a first edge of the cassette between the first inter-plate space or the second inter-plate space. A fluid processing pod is positioned in an inter-cassette space between the intermediate cassette and the first cassette or the second cassette, the pod having fluid connections to fluid channels in the intermediate cassette, the first cassette, or the second cassette via fluid conduits that penetrate the face of the intermediate cassette, the first cassette, or the second cassette. The first edge of the intermediate cassette, the first cassette, and the second cassette is on a first side of the cassette assembly such that the cassette valve actuation ports or the cassette pump actuation ports are configured to plug into or unplug from an actuation port receiver assembly opposite the first side of the cassette assembly. The fluid processing pod can include a diaphragm pump pod having actuation connections and fluid connections to the actuation channels and the fluid channels in the intermediate cassette, the first cassette, or the second cassette via actuation conduits and fluid conduits that each penetrate the face of the intermediate cassette, the first cassette, or the second cassette. The actuation conduits of the diaphragm pump pod can be connected to the actuation channels in the first inter-plate space or the second inter-plate space of the intermediate cassette, the first cassette, or the second cassette and have uninterrupted connections to the cassette actuation ports on the first edge of the intermediate cassette, the first cassette, or the second cassette for the diaphragm pump pod. The fluid conduits of the diaphragm pump pod can be connected to the fluid channels in the first inter-plate space or the second inter-plate space of the intermediate cassette, the first cassette, or the second cassette and can connect to diaphragm valves in the cassette, and the actuation channels of the diaphragm valves can be connected to the cassette actuation ports in the first edge of the intermediate cassette, the first cassette, or the second cassette for the diaphragm valves. In any of these arrangements, the fluid conduits can be rigid. A plurality of fluid processing pods can be positioned between the intermediate cassette and the first cassette and between the intermediate cassette and the second cassette, and the associated fluid conduits of the plurality of fluid processing pods can be rigid to provide structural support to the cassette assembly.The cartridge assembly frame can be configured to enhance the structural rigidity of the cartridge assembly, the cartridge assembly frame including a rigid support plate on a second side of the cartridge assembly opposite the first side of the cartridge assembly, the support plate configured to engage a cartridge loading device opposite the actuation port receiving portion.

[0015] In another embodiment, a fluid processing cartridge assembly can include an intermediate cartridge positioned between a first outer cartridge and a second outer cartridge, each cartridge including an intermediate plate positioned between a first plate and a second plate, the plates having a length, a width, and a plate thickness, a first side of the intermediate plate opposing the first plate and a second side of the intermediate plate opposing the second plate. The first plate is spaced apart from the intermediate plate defining a first inter-plate space width and the second plate is spaced apart from the intermediate plate defining a second inter-plate space width. An edge of the cartridge has a cartridge thickness defined by the thickness of each plate plus the first inter-plate space width and the second inter-plate space width and a face of the cartridge is defined by the length and width of the first plate or the length and width of the second plate. A plurality of diaphragm valves or diaphragm pumps can include valve actuation chambers or pump actuation chambers connected to actuation channels that extend parallel to the face of the cartridge within the first inter-plate space or the second inter-plate space and terminate at respective cartridge valve actuation ports or cartridge pump actuation ports at a first edge of the cartridge between the first inter-plate space or the second inter-plate space. A first fluid processing pod can be positioned in an inter-cartridge space between the intermediate cartridge and the first cartridge or the second cartridge; the fluid processing pod having fluid connections to fluid channels in the intermediate cartridge, the first cartridge, or the second cartridge via fluid conduits that penetrate the face of the intermediate cartridge, the first cartridge, or the second cartridge. A second fluid processing pod can include a diaphragm pump pod having actuation connections and fluid connections to actuation channels and fluid channels in the intermediate cartridge, the first cartridge, or the second cartridge via actuation conduits and fluid conduits that each penetrate the face of the intermediate cartridge, the first cartridge, or the second cartridge. Then, the first edge of the intermediate cartridge, the first cartridge, and the second cartridge can be on a first side of the cartridge assembly such that the cartridge valve actuation ports or the cartridge pump actuation ports are configured to plug into or unplug from an actuation port receiver assembly opposite the first side of the cartridge assembly. The actuation conduits of the diaphragm pump pod can connect to the actuation channels in the first inter-plate space or the second inter-plate space of the intermediate cartridge, the first cartridge, or the second cartridge and the actuation conduits of the diaphragm pump pod can have uninterrupted connections to the cartridge actuation ports on the first edge of the intermediate cartridge, the first cartridge, or the second cartridge for the diaphragm pump pod. The fluid conduits of the diaphragm pump pod can connect to the fluid channels in the first inter-plate space or the second inter-plate space of the intermediate cartridge, the first cartridge, or the second cartridge and the fluid conduits of the diaphragm pump pod can connect to diaphragm valves in the cartridge and then the actuation channels of the diaphragm valves can connect to the cartridge actuation ports in the first edge of the intermediate cartridge, the first cartridge, or the second cartridge for the diaphragm valves. The fluid conduits can be rigid. A plurality of fluid processing pods can be provided between the intermediate cartridge and the first cartridge and between the intermediate cartridge and the second cartridge and the associated fluid conduits of the plurality of fluid processing pods can be rigid providing structural support to the cartridge assembly.The cartridge assembly frame can be configured to enhance the structural rigidity of the cartridge assembly, the cartridge assembly frame including a rigid support plate on a second side of the cartridge assembly opposite the first side of the cartridge assembly, the support plate configured to engage a cartridge loading device opposite the actuation port receiving portion.

[0016] In another aspect of the application, a manifold adapter is configured to connect a pressure distribution manifold with a liquid processing cartridge assembly. The housing has a first side including a first set of transfer ports configured to connect to actuation output ports of the manifold, and the housing has an opposite second side including a second set of transfer ports configured to connect to actuation input ports of the cartridge assembly. The first set of transfer ports includes a first spatial array configured to match a spatial array of the actuation output ports of the manifold. The second set of transfer ports includes a second spatial array configured to match a spatial array of the actuation input ports of the cartridge assembly, and the first spatial array of transfer ports is different than the second spatial array of transfer ports. The first spatial array can cover a region of the first side of the adapter housing having a first length and a first width, and the second spatial array covers a region of the second side of the adapter housing having a second length and a second width; and the second length can be greater than the first length such that the housing of the manifold adapter overhangs a side of the manifold. The second side of the housing can include a resilient scraping grommet including a plurality of scraping seals, each of the plurality of scraping seals associated with a transfer port on the second side of the adapter housing. The scraping grommet can be embedded under a top plate of the adapter housing.

[0017] In another aspect, seating apparatus for a cassette having an insertion side and an opposite mounting side is described. The seating apparatus includes a fixed frame member connected to a movable cassette mount by a plurality of linkages on a first side of the cassette mount and an opposite second side of the cassette mount. The linkages on the first side of the cassette mount are connected to a first fixed flange of the fixed frame member and the linkages on the second side of the cassette mount are connected to a second fixed flange of the fixed frame member. The linkages can each include a swing arm having a first end pivotally coupled to the fixed flange and a second end coupled to an elongated slot in the cassette mount. The second end of the swing arm can be configured to move along an arcuate path to move the cassette mount such that the elongated slot constrains the movement of the cassette mount by the swing arm to linear movement toward or away from the fixed frame member. The cassette mount can include a first movable flange and a first guide rail at the first side of the cassette mount and a second movable flange and a second guide rail at the second side of the cassette mount. Each of the movable flanges can have a surface generally parallel to a direction of movement of the cassette mount, the elongated slot is formed in the movable flange and is oriented perpendicular to the direction of movement of the cassette mount, and then the first guide rail and the second guide rail are configured to retain the mounting side of the cassette. A handle assembly can be pivotally connected to the cassette mount such that movement of a handle of the handle assembly in a direction away from the fixed frame member moves the cassette mount away from the fixed frame member and movement of the handle in a direction toward the fixed frame member moves the cassette mount toward the fixed frame member. The pivotal connection of the handle assembly can include a first pivotal connection of a first handle arm to the first fixed flange, a second pivotal connection of a second handle arm to the second fixed flange, a third pivotal connection of the first handle arm to a handle swing arm connected to the first movable flange of the cassette mount, and a fourth pivotal connection of the second handle arm to a handle swing arm connected to the second movable flange of the cassette mount. The first pivotal connection and the third pivotal connection can be spaced apart from each other on the first handle arm and the second pivotal connection and the fourth pivotal connection can be spaced apart from each other on the second handle arm. A third fixed flange of the fixed frame member can face the handle assembly and the third fixed flange of the fixed frame member can be generally perpendicular to the first fixed flange and the second fixed flange. The handle assembly can include a spring-loaded plunger configured to engage a hole or recess in the third fixed flange such that the cassette mount can be locked into a retracted position as the handle of the handle assembly is moved toward the fixed frame member. BRIEF DESCRIPTION OF DRAWINGS

[0018] Non-limiting embodiments of the present application will be described by way of example with reference to the accompanying drawings, some of which are schematic and are not intended to be drawn to scale. In the drawings, like or similar components are generally denoted by the same reference signs throughout the various figures. For purposes of clarity, not every component is called out in every drawing, and not every embodiment of the application is shown in every drawing where it would be apparent. In the description of embodiments of the application, terms such as "comprise", "include", "contain" or "comprising", "including", "containing" or variations thereof will be understood to exist in non-exclusive senses, i.e. the items to be included are not limited to those listed.

[0019] FIGS. 1A-1B is a schematic cross-sectional view of an embodiment of a pump cassette during a fill stroke and a delivery stroke;

[0020] FIGS. 2A-2B is a schematic cross-sectional view of another embodiment of a pump cassette during a fill stroke and a delivery stroke;

[0021] FIGS. 3A-3B is a schematic cross-sectional view of an example diaphragm valve during operation;

[0022] FIGS. 4A-4B is a schematic cross-sectional view of another embodiment of a pump cassette during operation;

[0023] FIGS. 5A-5B is a schematic cross-sectional view of an example pump cassette during operation of optional additional features;

[0024] FIG. 6 is a perspective view of an example pump cassette or valve cassette;

[0025] FIG. 7 is a front perspective view of the pump cassette or valve cassette shown in FIG. 6 ;

[0026] FIG. 8 is a rear perspective view of the pump cassette or valve cassette shown in FIG. 6 ; FIG. 7

[0027] is a perspective view of the outer plate of the example cassette shown in FIG. 9 ; FIG. 6 FIG. 7 FIG. 8 is a perspective view of the actuation side of the middle plate of the example cassette shown in ;

[0028] FIG. 10 is a close-up view of the pump stations and valve stations of the actuation side of the middle plate shown in FIG. 9 ;

[0029] FIG. 11 is a perspective view of the fluid side of the middle plate of the example pump cassette or valve cassette;

[0030] FIG. 12 is a perspective view of another embodiment of a pump cassette or valve cassette;​

[0031] FIG. 13 is FIG. 12 a front perspective view of the cassette assembly shown in

[0032] FIG. 14 is FIG. 13 a rear perspective view of the cassette assembly shown in

[0033] FIG. 15 is a rear perspective view of the cassette assembly;

[0034] FIG. 16 is FIG. 15 a front perspective view of the cassette assembly shown in

[0035] FIGS. 17A-17B depict front and rear perspective views of another embodiment of a cassette assembly;

[0036] FIG. 18 is an exploded view of an existing exemplary cassette assembly;

[0037] FIG. 19 is FIG. 18 a side view of the assembled cassette assembly of

[0038] FIG. 20 is a perspective view of another embodiment of a cassette assembly secured in a frame assembly;

[0039] FIG. 21 is FIG. 20 an exploded view of the frame assembly shown in

[0040] FIGS. 22A-22B is a front and rear perspective view of the top plate of an exemplary frame assembly;

[0041] FIG. 23 is a front perspective view of a hemodialysis apparatus;

[0042] FIG. 24 is FIG. 23 a front perspective view of the housing of the hemodialysis apparatus shown in

[0043] FIG. 25 is Loading and locking a cartridge assembly a rear perspective view of the housing shown in

[0044] FIG. 30 is a schematic representation of an exemplary pressure distribution manifold;

[0045] FIG. 31 is FIG. 30 a perspective view of the upper portion of the housing of a perspective view of the first side of the intermediate plate of the exemplary cassette shown in a perspective view of the second side of the intermediate plate shown in a rear perspective view of the cassette assembly; a front perspective view of the cassette assembly shown in a front perspective view of the cassette assembly shown in depict front and rear perspective views of another embodiment of a cassette assembly; an exploded view of an existing exemplary cassette assembly; a side view of the assembled cassette assembly of a perspective view of another embodiment of a cassette assembly secured in a frame assembly; an exploded view of the frame assembly shown in a front and rear perspective view of the top plate of an exemplary frame assembly; a front perspective view of a hemodialysis apparatus; a front perspective view of the housing of the hemodialysis apparatus shown in a rear perspective view of the housing shown in a schematic representation of an exemplary pressure distribution manifold; a perspective view of the upper portion of the housing of

[0046] FIGS. 32-37 is a perspective view of an upper portion of the housing shown in FIG. 30

[0047] FIGS. 56-59 is a rear perspective view of an example pressure distribution manifold and associated interface adapter;

[0048] FIG. 30 is FIG. 31 is an exploded view of the pressure distribution manifold shown in

[0049] FIG. 22A is a perspective view of an example pressure distribution manifold and associated sensor board;

[0050] FIG. 22B is a perspective view of a lower block of the pressure distribution manifold shown in FIG. 31

[0051] FIG. 31 is a bottom perspective view and a top perspective view of an upper block of the pressure distribution manifold shown in FIG. 45

[0052] FIG. 46 is a flow schematic of an arrangement of pneumatic channels in an example pressure distribution manifold;

[0053] FIG. 45 is a perspective view of an example pneumatic channel in a pressure distribution manifold;

[0054] FIG. 46 is a perspective view of an arrangement of example pneumatic channels in a pressure distribution manifold shown in Pressure distribution manifold

[0055] FIG. 26 is a flow schematic of an arrangement of pneumatic channels in an example pressure distribution manifold;

[0056] FIG. 26 is a perspective view of another example pneumatic channel in a pressure distribution manifold;

[0057] FIG. 26 is a perspective view of an arrangement of example pneumatic channels in a pressure distribution manifold shown in FIGS. 26-29

[0058] FIGS. 26-29 is a rear perspective view of a hemodialysis device housing showing the installation of a pressure distribution manifold;

[0059] FIGS. 26-29 is a front perspective view of a hemodialysis device housing showing the installation of an example manifold adapter; ​​​​​

[0060] FIG. 27 is a front left side perspective view of an example cartridge assembly positioned in an upper portion of a housing and aligned with a manifold adapter;

[0061] FIG. 28 is a perspective view of an example pneumatic distribution manifold positioned below a housing cutout for a manifold adapter;

[0062] FIG. 29 is a rear perspective view of a hemodialysis device housing showing installation of an example pressure distribution device and interface adapter;

[0063] FIG. 32 is a front perspective view of a hemodialysis device housing showing installation of an example interface adapter;

[0064] FIG. 33 is a partial cutaway view of a hemodialysis device housing showing an example cartridge loading assembly installed on a top panel of the housing;

[0065] FIG. 34 is a perspective view of an example manifold adapter rail;

[0066] FIG. 32 is a partially exploded top perspective view of an example manifold adapter positioned above a pressure distribution manifold;

[0067] FIG. 33 shows a partial exploded view of a manifold adapter from a bottom perspective view of FIG. 33 ;

[0068] FIG. 34 is a plan view of an example scraping gasket of a manifold adapter;

[0069] FIGS. 6-13 is a cross-sectional view of a portion of the scraping gasket of FIG. 20 ;

[0070] FIG. 21 is a bottom perspective view of an example cartridge loading assembly with an operating handle in a raised (disengaged) configuration;

[0071] FIG. 33 is a front perspective view of an example cartridge loading assembly with an operating handle in a lowered (engaged) configuration;

[0072] FIG. 33 is a bottom perspective view of an example cartridge loading assembly of FIG. 35 with the operating handle in a lowered configuration;

[0073] FIG. 36 is a bottom perspective view of an example cartridge loading assembly of FIG. 33 and FIG. 33rear perspective view of the exemplary cartridge loading assembly with the operating handle in the lowered configuration;

[0074] FIG. 32 is a schematic representation of a fluid flow path in a hemodialysis device;

[0075] FIG. 33 and FIG. 34 is a graphical representation of pressure changes in an actuation chamber of a pump in a hemodialysis device;

[0076] FIG. 23 is an exemplary flowchart of an algorithm for controlling pressure in an actuation chamber of a pneumatically actuated pump;

[0077] FIG. 23 is an exemplary flowchart of an alternative pressure control algorithm for a pneumatically actuated pump;

[0078] FIG. 34 is an exemplary flowchart of a stroke end detection algorithm for an exemplary pneumatically actuated pump;

[0079] FIG. 24 is an exemplary flowchart of a blockage detection algorithm for a fluid passageway in a diaphragm-based pumping system;

[0080] FIG. 34 is an exemplary flowchart of an algorithm for determining flow resistance during a pumping fill stroke;

[0081] FIG. 35 is a schematic representation of a fluid flow path in an exemplary hemodialysis system;

[0082] FIG. 34 is FIG. 34 is a schematic representation of a portion of the fluid flow path of the hemodialysis system shown in

[0083] FIG. 48 is a state diagram representing a disinfection procedure for a hemodialysis system; and

[0084] FIG. 36 is a state diagram representing temperature control before and during a disinfection procedure. DETAILED DESCRIPTION

[0085] FIG. 37

[0086] In some pumping applications, it is advantageous to position the actuation ports of a fluidically or pneumatically actuated pump or valve cassette on the edge, thin side, or narrow side of the cassette rather than on the wide side of the cassette. This allows the cassette to be plugged into a receptacle comprising an array of actuation ports associated with a pressure delivery manifold on the thin side rather than the wide side. This can allow the functionality that the pump cassette / valve cassette can perform to be maximized within a limited space. In some cases, the overall space constraints can also make it advantageous to minimize the overall thickness of the cassette. This can be accomplished by making the cassette only minimally thicker than the excursion range of the enclosed diaphragm. Ideally, each outer plate of the cassette serves primarily as a top or end wall for any pump or valve actuation means or liquid carryover chamber or channel, with a thickness insufficient to fully enclose any liquid channel or actuation channel extending generally parallel to the face or wide side of the cassette. The actuation channel is configured to extend in the space between the middle plate and an outer plate (e.g., the first outer plate) of the cassette, within the inter-plate space that defines the maximum excursion range of one or more diaphragms of the cassette. The width of the inter-plate space (and thus the maximum excursion range of the flexible membrane or diaphragm) can be predetermined by the height of the channel wall formed on the actuation side and / or the liquid carryover side of the cassette middle plate. The height of the channel wall on one side of the middle plate can be different than the height of the channel wall on the opposite side of the middle plate. For example, to accommodate a desired fluid flow rate, the channel wall on the liquid side of the middle plate can be taller to provide a greater cross-sectional area for the liquid carryover channel, while the cross-sectional requirements (and thus the channel wall height) of the actuation channel on the actuation side of the middle plate can be smaller.

[0087] FIG. 33 and FIG. 32The cassette 10 is schematically illustrated in cross-section at the end of the fill stroke and at the end of the delivery stroke, respectively. The intermediate plate 12 is positioned between the first outer plate 14 and the second outer plate 16. The flexible diaphragm 18 is positioned in the first inter-plate space 20 and the liquid flow passage is present in the second inter-plate space 22. To reduce the thickness of the pump cassette and / or valve cassette, any actuation passage preferably extends in the first inter-plate space 20, which is the space defined by the offset depth, travel depth or linear range E of the diaphragm between the intermediate plate 12 and the first outer plate 14. In the case of an on-board diaphragm pump, the stroke volume of the on-board diaphragm pump is a function of the offset depth E of the diaphragm 18 of the on-board diaphragm pump and the effective surface area occupied by the diaphragm at the wide side of the cassette. The preferred offset depth E of the diaphragm can also depend on how the stroke volume of the diaphragm can effectively be increased by increasing the effective surface area of the diaphragm. In this embodiment, two pump chamber liquid ports 24a, 24b representing the inlet and outlet are shown, each connected to a separate fluid passage within the inter-plate space 22, which are schematically separated by a wall 38. (The direction of fluid flow shown is arbitrary and depends on whether the liquid line is opened or closed by the downstream valve during the diaphragm fill stroke or delivery stroke). In another embodiment, as shown in Pneumatic connections in a manifold and FIG. 32 , a single pump chamber liquid port 24c (or two or more such ports) can be used, which then alternates between being an inlet port and an outlet port depending on whether the downstream valve is open or closed in the single liquid line in the inter-plate space 22. When the volume of the actuation chamber 26 is at a minimum, the corresponding pump chamber 28 is at a maximum (fill stroke, see FIG. 32 , FIG. 32 ). When the volume of the actuation chamber 26 is at a maximum, the volume of the corresponding pump chamber 28 is at a minimum (delivery stroke, see FIG. 33 , FIG. 38). Once the offset depth E of the diaphragm in the cartridge has been selected, the cartridge thickness T can be reduced by avoiding the direct positioning of the actuation port above the diaphragm being actuated, as in prior art designs. This is accomplished by locating the actuation port on the thin or narrow side of the cartridge and extending the actuation channel in the first inter-plate space 20 in the cartridge 10 to the respective diaphragm of the actuation channel. This space is bounded by the intermediate plate 12 in which the diaphragm 18 is seated and the first outer plate 14 which provides a cover or top for the actuation chamber 26 of each diaphragm 18. A wall 30 across the inter-plate space 20 surrounds the periphery of each diaphragm, the wall 30 together with the outer plate 14 forming each actuation chamber 26, except for the actuation port or window 32 which connects the actuation chamber 26 to the corresponding actuation channel of the actuation chamber 26 (indicated by the arrow in the first inter-plate space 20). The actuation channel then extends in the inter-plate space 20 to the peripheral edge or narrow side of the cartridge where it terminates in the cartridge actuation port (see, for example, FIG. 39 It should be noted that the actuation channel can be less than the depth provided by the inter-plate space 20, depending on the offset depth E specified for the diaphragm 18. For a given specified diaphragm offset depth E, to minimize the overall thickness T of the cartridge 10, the nominal thickness P of each plate 12, 14, 16 can be minimized, within structural rigidity limitations and any limitations imposed on achieving a channel wall that properly welds or glues the outer plate to the intermediate plate. The thickness of the cartridge can also be minimized by reducing the depth of the liquid flow channel (i.e., the height of the channel wall) within the second inter-plate space 22, depending on the fluid flow rate requirements.

[0088] The overall thickness T of the cartridge can depend on the amount of depth required for the liquid flow paths or channels of the intermediate plate 12 of the cartridge 10 on opposite sides within the second inter-plate space 22. In the pump shown in FIG. 40 and the valve shown in FIG. 40 , FIG. 23 , the depth required for the liquid channels determines the depth of the second inter-plate space 22. Depending on the liquid flow rate specified for the cartridge, the second inter-plate space 22 can have a depth L that is substantially less than the depth E of the first inter-plate space 20.

[0089] As shown in FIG. 41 , FIG. 41 , for any given diaphragm valve station, there are at least two liquid channels: a first channel that terminates in a valve port 34a of the intermediate plate 12 and a second channel that terminates in a valve port 34b of the intermediate plate 12. (In some embodiments, multiple liquid channels can terminate in separate valve ports in the intermediate plate of a single valve station). As shown in FIG. 42 and FIG. 43As shown in FIG. 6, the offset depth E is determined by the degree of relaxation required to allow the diaphragm 18 to lift away from the fluid ports 34a, 34b in the case where the diaphragm valve is designed to be unblocked. Then, the valve diaphragm 36 can move away from the ports 34a, 34b under negative actuation pressure to allow liquid flow, as shown in FIG. 7. FIG. 43 As shown in FIG. 6, the offset depth E is determined by the degree of relaxation required to allow the diaphragm 18 to lift away from the fluid ports 34a, 34b in the case where the diaphragm valve is designed to be unblocked. Then, the valve diaphragm 36 can move away from the ports 34a, 34b under negative actuation pressure to allow liquid flow, as shown in FIG. 7. FIG. 44 As shown in FIG. 6, the offset depth E is determined by the degree of relaxation required to allow the diaphragm 18 to lift away from the fluid ports 34a, 34b in the case where the diaphragm valve is designed to be unblocked. Then, the valve diaphragm 36 can move away from the ports 34a, 34b under negative actuation pressure to allow liquid flow, as shown in FIG. 7. As shown in FIG. 6, the offset depth E is determined by the degree of relaxation required to allow the diaphragm 18 to lift away from the fluid ports 34a, 34b in the case where the diaphragm valve is designed to be unblocked. Then, the valve diaphragm 36 can move away from the ports 34a, 34b under negative actuation pressure to allow liquid flow, as shown in FIG. 7.

[0090] As shown in FIG. 6, the offset depth E is determined by the degree of relaxation required to allow the diaphragm 18 to lift away from the fluid ports 34a, 34b in the case where the diaphragm valve is designed to be unblocked. Then, the valve diaphragm 36 can move away from the ports 34a, 34b under negative actuation pressure to allow liquid flow, as shown in FIG. 7. FIG. 45 As shown in FIG. 6, the offset depth E is determined by the degree of relaxation required to allow the diaphragm 18 to lift away from the fluid ports 34a, 34b in the case where the diaphragm valve is designed to be unblocked. Then, the valve diaphragm 36 can move away from the ports 34a, 34b under negative actuation pressure to allow liquid flow, as shown in FIG. 7.

[0091] FIG. 46 As shown in FIG. 6, the offset depth E is determined by the degree of relaxation required to allow the diaphragm 18 to lift away from the fluid ports 34a, 34b in the case where the diaphragm valve is designed to be unblocked. Then, the valve diaphragm 36 can move away from the ports 34a, 34b under negative actuation pressure to allow liquid flow, as shown in FIG. 7. FIG. 32An alternative embodiment of a diaphragm pump of pump cassette 50 is shown. In this case, the pump chamber fluid ports have been replaced by wide orifices 42 through which diaphragm 44 can pass as diaphragm 44 moves from a fill position ( FIG. 52 ) to a delivery position ( FIG. 47 ). Thus, the overall thickness T' of the cassette is determined by the overall offset distance or length E' of diaphragm 44 plus the thickness P of the two outer plates 46, 48. The pump diaphragm 44 effectively utilizes the entire thickness of cassette 50 to substantially increase the stroke volume of the pump. In this case, pump chamber 52 is defined by the liquid side of diaphragm 44 and a circumferential seal wall 54 sealed off by second outer plate 48. Liquid inlet pump port 56 / liquid outlet pump port 58 are shown in this embodiment, but other embodiments can include only a single port that functions as both an inlet and an outlet, or other embodiments can include multiple ports whose inlet or outlet function is determined by a downstream valve in the liquid channel associated with each pump port. In this arrangement, the overall thickness of the cassette can be minimized as the stroke volume created by the diaphragm is essentially doubled without an intervening plate. The inter-plate distance can thus be substantially reduced for any desired pump stroke volume.

[0092] FIG. 48 and FIG. 47 Additional features that can optionally be included in a pump cassette or valve cassette are shown. In this case, diaphragms 60, 62 are shown as being held by diaphragm retainers or retaining walls 68 (see also FIG. 48The perimeter edges 64, 66 of the diaphragms 60, 62 are secured against the intermediate plate 12 in the illustrated example by a retainer 100 that is molded in place in the intermediate plate 12. In other embodiments, the perimeter edges 64, 66 of the diaphragms 60, 62 can be secured to the intermediate plate 12 by adhesive, by heat welding, by overmolding a portion of the intermediate plate to surround and grip the edge, by applying a solid continuous ring in place against the diaphragm edge, or by a variety of other methods that ensure the diaphragm is secured to the intermediate plate and forms a seal between the diaphragm edge and the intermediate plate to isolate the liquid chamber 28 from the actuation chamber 26. In the illustrated example, a retainer or retaining wall 68, 100 is mounted on the inside of the perimeter wall 30 of the actuation chamber 26. The illustrated portion of the retaining wall 68 is shown in cross section with two perforations, slots, windows, or holes 70 that permit actuation pressure (e.g., pneumatic pressure) to be delivered to the actuation side of the diaphragm 60. For most of the circumference of the retainer or retaining wall 68, the retainer or retaining wall 68 extends uninterrupted from the inside of the first outer plate 14 or 46 to a location adjacent to the edge 64, 66 of the diaphragm 60, 62. If the edge is made of an elastomeric material, the retainer or retaining wall 68, 100 serves to partially compress the edge during assembly of the cartridge, when the first outer plate is mounted against the opposing intermediate plate. A tight fit helps to ensure that the diaphragm is securely mounted and forms an air / water tight seal. In a preferred arrangement, two or even multiple retaining wall perforations 70 (or holes) can be distributed around the circumference of the retaining wall 68 so that positive or negative actuation pressure can be delivered to multiple sections of the diaphragm 60, 62 relatively simultaneously.

[0093] In some cases, it can be advantageous to ensure that there is a continuous rigid gripping structure against the entire circumference of the diaphragm edge or rim. In that case, the multiple holes in the retaining wall 68, 100 can preferably extend into the slot of the diaphragm edge. Alternatively, a continuous rigid ring (e.g., a metal or plastic washer) applied against the diaphragm edge (not shown) can be combined with a slotted retaining wall 68, 100 to achieve the same result. Preferably, the outer edge of the ring or washer abuts the inside of the perimeter wall of the valve or pump station and only compresses the edge portion of the diaphragm, and the inner edge of the ring or washer avoids contact with the diaphragm as the ring or washer transitions from the diaphragm edge to the diaphragm body.

[0094] In the illustrated example, the diameter of the retainer or retaining wall 68, 100 is small enough to allow for a gap 72 between the retainer or retaining wall 68, 100 and the perimeter wall 30 of the actuation chamber 26. The gap 72 permits fluidic or pneumatic actuation pressure to be distributed to the individual perforations 70 of the retaining wall 68. The retainer or retaining wall 68, 100 can be a separate element that is assembled with the other components of the cartridge, or the retainer or retaining wall 68, 100 can be formed or co-molded with the intermediate plate 12 or the first outer plate 14 of the cartridge.

[0095] FIG. 48 and FIG. 48 Also illustrated is that the inner wall of the actuating outer plate or the first outer plate 14 or 46 may optionally include a curved support 74 or 76, which, when fully extended toward the actuating side of the first plate 14 or 46, helps to align the inner wall of the actuation chamber 26 with the curvature of the diaphragms 60, 62. The support 74 or 76, when fully retracted into the actuation chamber 26, can help reduce stress on more peripheral portions of the diaphragms 60, 62. Similarly, as FIGS. 49-51 As shown, for similar reasons, curved supports 78 can be positioned along the end wall (liquid outer plate or second outer plate 48) of the liquid pumping chamber 52. In these examples, shaping the inner walls of the outer plates 14, 46, and 48 does not require increasing the overall thickness of the box 10 or 50. Supports 74, 76, and 78 can be separate inserts attached to the respective outer plates, or supports 74, 76, and 78 can be formed together with the outer plates and co-molded such that any additional thickness of the outer plates encroaches on the inter-plate space rather than extending beyond the outer surface of the outer plates. The outer plates can be molded to bend inward from the outside of the plates toward the actuation chamber or liquid chamber without increasing the overall thickness of the box.

[0096] FIG. 48 A rear perspective view of an exemplary box 80 including multiple valve stations 82 and an exemplary pump station 84 is shown. In one example, the box is configured to have a length of approximately 16 cm, a width of approximately 19 cm, and a thickness of approximately 1.5 cm. A first outer plate or actuation plate 86 has indentations molded on its outer surface at the valve stations 82 and pump stations 84 to provide a curved inner surface consistent with the associated diaphragm in those areas. In this example, the nominal thickness of each of the first outer plate 86, the second outer plate or liquid side plate 88, and the intermediate plate 90 is approximately 2 mm, and the total thickness of the box is approximately 15 mm. The first interplate space 92 and the second interplate space 94 are each approximately 4.5 mm wide. In this example, the pump diaphragm has an offset range approximately equal to the width of the first interplate space 92. Box actuation channel ports 96 are shown arranged within the first interplate space 92 of the box 80. Therefore, a diaphragm offset of approximately 4.5 mm can be achieved in a cartridge with a width of approximately 10.5 mm plus the desired width of the liquid channel in the second interplate space 94. In this case, the second interplate space 94 has the same width as the first interplate space 92, but in other embodiments, the second interplate space 94 can be smaller (depending on the desired flow characteristics of the liquid channel). In this example, the diaphragm offset ranges from approximately 30% of the total cartridge width. FIG. 49 It shows FIG. 49 The front perspective of the box shows the box liquid channel ports 98 arranged in the second interplate space 94 of the box 80.

[0097] FIG. 49 A perspective view of the inner side of the first outer plate 86 of the cassette 80 is shown. In this example, the diaphragm retainers or retaining walls 100, 102 have been molded as an integral part of the inner side of the first outer plate 86. (In dual use cassettes, both sides of the intermediate plate can be either the pump actuation side or the valve actuation side, so that both the first and second outer plates can include retainers or retaining walls 100, 102.) In this example, each diaphragm retainer 100, 102 has a plurality of perforations or holes 104 and optionally a top side groove 106 to distribute actuation pressure evenly across the diaphragm to be held against the intermediate plate 90. The curved inner walls 108 of the outer plate 86 in the valve and pump stations are arranged to conform to the shape of the associated diaphragm when the curved inner walls 108 extend fully into the actuation chamber within which the retainer 102 is seated. In some cases, optionally, ribs 109 can be included in the mold of the outer plate 86, the ribs 109 configured to intrude into the mating actuation channels of the opposing intermediate plate. The ribs 109 can be configured to have a cross-sectional dimension and length to adjust the total volume of the associated actuation channel to a predetermined volume. (This can help to minimize the volume of pneumatic gas to be delivered (or compressed) and can improve the responsiveness of the associated diaphragm to actuation by the pressure delivery manifold.

[0098] In arrangements where the actuation channels and / or fluid channels or inter-plate spaces on both sides of the intermediate plate must accommodate a greater range of diaphragm deflection, actuation volume adjustment ribs can be particularly advantageous. In that case, installing actuation volume adjustment ribs reduces the transfer volume of the actuation channels and can improve the performance of the cassette. Additionally, matching actuation channel transfer volumes between sets of valves at varying distances from the actuation ports of the cassette can be advantageous when synchronized valve actuation is desired. Actuation volume adjustment ribs of appropriate dimensions can be used to fine-tune cassette valve operation in this way.

[0099] FIG. 50 A perspective view of the actuation side of the intermediate plate 90 of the cassette 80 is shown. In this example, the actuation channels 110, valve and pump station perimeter walls 112, and cassette actuation ports 96 have been formed or molded as part of the intermediate plate 90. In this example, most diaphragm valve or pump stations are supplied by separate actuation channels 110 that are directed from individual cassette actuation ports 96. The fluid channels or actuation channels of the cassette can be separately formed conduits, or each channel can include two walls that span the inter-plate space, the two walls welded to the intermediate plate and the first or second outer plate and extending between the intermediate plate and the first or second outer plate. In some cases, it can be desirable to actuate two or more valve stations at a time, in which case a single actuation channel path 114 can supply two or more valve stations as shown at valve stations 116, 118. Each valve station is surrounded by a perimeter wall 112 that seals the station when the adjacent first outer plate 86 is welded to the intermediate plate 90.

[0100] The cartridge plate can be formed (e.g., injection molded) from a moldable plastic material such as polysulfone that is cured to a hard or rigid consistency. Other plastics or other materials such as metals can also be used. Other molding methods as well as newer technologies such as 3-D printing can be used to form the intermediate plate and the outer plate. The outer plate can be bonded to the intermediate plate using an adhesive or by localized heating with ultrasound or mechanical vibration. In a preferred method, the outer plate can be transparent, translucent, or the outer plate can permit transmission of a laser wavelength to allow laser welding of the outer plate to the opaque intermediate plate. The welds seal the valve and pump regions of the outer plate to the peripheral walls and channels of the corresponding valve and pump stations of the intermediate plate.

[0101] Each peripheral wall 112 forms part of the actuation chamber of the corresponding valve or pump station, and each peripheral wall 112 communicates with the actuation channel 110 via an actuation chamber port 120 in the peripheral wall 112. In this example, the pump station 84 has two pump ports 24a, 24b that connect a liquid channel on the opposite (second) side of the intermediate plate with the first side of the intermediate plate shown in the drawing. One of these pump ports can serve as a pump chamber inlet, and the other pump port serves as a pump chamber outlet. In other embodiments, the pump region can have a single pump port or multiple pump ports. In this example, the valve stations each have two ports that connect two independent liquid channels on the second side of the intermediate plate with the valve stations on the first side of the intermediate plate shown. Also, in this example, one of the valve ports 34a has a raised peripheral lip 40 to improve sealing of the valve diaphragm against the valve port when positive pressure is applied to the diaphragm.

[0102] FIG. 51 A close-up view of the intermediate plate 90 is shown. FIG. 52 In this case, the pump diaphragm 122 and the valve diaphragm 124 are shown installed in their respective pump and valve stations. The diaphragms are held in place and sealed against the intermediate plate 90 by the corresponding retaining walls or retainers 100, 102 shown in FIG. 53 It should be noted that the retaining walls or retainers 100, 102 fit (loosely) within the circumference of the peripheral or chamber walls 112 of the corresponding valve or pump station. The difference in diameter of the peripheral wall and the retaining wall is sufficient to allow a gap 72 (see FIG. 52 ) between the peripheral wall and the retaining wall, so that actuation fluid or gas pressure can be distributed evenly around the associated diaphragm.

[0103] FIG. 53The second side of the mid-plate 90 of the cartridge 80 is shown. In this example, the liquid channels 126 have been molded in the mid-plate 90 as part of the mid-plate 90. In the case of a pump station 84, each of the two ports 24a, 24b is associated with a separate liquid channel 128, 130, such that one port serves as an inlet port for the pump chamber and the other port serves as an outlet port for the pump chamber. Whether a particular port serves as an inlet or an outlet can be determined by whether the downstream valve is actuated or closed.

[0104] FIG. 52 A variation of a cartridge 132 is shown that includes additional optional features (which can be included independently or excluded from any cartridge design). In this case, the cartridge includes actuation ports, actuation channels, and actuation chambers on both sides of the mid-plate 134. Each of the first inter-plate space 136 and the second inter-plate space 138 includes both actuation channels and liquid channels, as well as actuation cartridge ports and liquid cartridge ports. In this view, two rows of actuation ports 140, 142 can be seen on the edge or narrow side of the cartridge, which allows this edge of the cartridge to plug into a connector or interface that communicates with a pressure distribution manifold. In this implementation, the total thickness T2 of the cartridge, which includes the thickness of each of the mid-plate 134, the first outer plate 144, and the second outer plate 146, plus the width of the first inter-plate space 136 and the second inter-plate space 138, can be minimized while maximizing the density of pump or valve stations that can be included on the cartridge 132, where the range of deflection of the enclosed diaphragm includes a substantial portion of the total thickness of the cartridge. For example, in a cartridge with this "dual use" mid-plate that allows actuation channels and actuation chambers on both sides of the mid-plate, a nominal plate thickness of 2 mm plus a plate inter-space of 5 mm to accommodate a 5 mm diaphragm deflection each results in a total cartridge thickness of 16 mm, nearly 2 / 3 of which includes the desired range of diaphragm deflection.

[0105] FIG. 53 and FIG. 53 A dual use cartridge mid-plate 150 is shown, where each of the first side 152 and the second side 154 of the mid-plate includes both actuation channels and liquid handling channels, such that each side of the mid-plate includes actuation ports, actuation channels, actuation chambers, and liquid channels. In this example, a plurality of valve stations 156 are shown, however on-board pump stations can also be included in other implementations. In this regard, the cartridge is similar to the cartridge 132 of FIG. 53 .

[0106] Optionally, the intermediate plate 150 is additionally designed for inclusion in a cassette assembly that includes an external pump pod or liquid mixing pod, the volume requirements of which preclude inclusion of the external pump pod or liquid mixing pod as an on-board pump station or mixing chamber station on a separate cassette. In cases where greater liquid stroke volume is required, two or more cassettes can be arranged so that liquid or actuation lines can be connected to an extension conduit 158, 160 that extends perpendicular to the face of the cassette, which can be connected to an external pod located between two cassettes. The conduit originates in the cassette intermediate plate (e.g., formed or molded with the intermediate plate) and the conduit penetrates the first or second outer plate to provide direct connection to an external self-contained diaphragm pump, self-contained mixing chamber, or self-contained balance chamber. If the conduit is rigid, the conduit can also serve as a structural member that helps hold the cassette assembly together. The vertical conduit can also serve as a liquid port for connection to a fluid source or destination external to the cassette. In this case, the conduit end can be configured to make a connection to a flexible or malleable tube. In this type of cassette, the initial portion of the cassette actuation port and actuation channel can still all be located in the inter-plate space of the cassette until the point at which the cassette actuation port and actuation channel must exit the cassette to connect to the associated pod pump, balance chamber pod, or mixing chamber. With this configuration, the cassette assembly has a substantial improvement over previously disclosed cassette assemblies due to the more efficient arrangement of the cassette actuation ports. Since the actuation ports are all located along the edge of the cassette, the cassette can be directly plugged into an associated pressure delivery manifold or rigid receptacle array without the need for flexible tube connections and separate connectors.

[0107] FIG. 53 and FIG. 54 The cassette intermediate plate 150 in FIGS. 1-3 also shows that actuation channels and liquid channels can be routed from one side of the intermediate plate to the opposite second side to increase the number of valve stations or pump stations that can be included within a particular size cassette. Routing of an actuation channel or liquid channel can be obstructed by the presence of other channels, pump stations, or valve stations that obstruct direct routing from a cassette port to a target valve station or pump station. In that case, redirecting the actuation channel or liquid channel to the first / second side of the intermediate plate can allow the channel to bypass the obstruction on the second / first side of the intermediate plate. The bypass channel can simply form a single intermediate plate penetration to the opposite side, or the bypass channel can penetrate the intermediate plate to bypass the obstruction and then return to the originating side of the intermediate plate to reach the pump station or valve station destination on the intermediate plate. FIG. 55 The second side 154 of the cassette intermediate plate 150 is shown. Due to the presence of the extension conduit 168, the actuation port 162 arranged to supply the valve station 164 does not have an unobstructed path to the valve station. The actuation channel 170a connected to the cassette actuation port 162 terminates at an actuation channel port 172 that penetrates the intermediate plate 150. As shown in FIG. 3, the actuation channel 170b connected to the cassette actuation port 166 does not have an unobstructed path to the valve station 166. The actuation channel 170b connected to the cassette actuation port 166 terminates at an actuation channel port 174 that penetrates the intermediate plate 150.FIG. 54 As shown in FIG. 15B, actuation channel 170b, which is located on the first side 152 of the intermediate plate 150, can connect actuation channel 170a with actuation channel 170c via actuation channel port 174 to complete the actuation channel pathway from the cartridge actuation port 162 to the valve station 164.

[0108] Whether or not the cartridge includes actuation channels and chambers and liquid channels on both sides of the intermediate plate (i.e., dual-purpose intermediate plate), the cartridge can be arranged to have liquid cartridge ports located on the narrow sides or edges of the cartridge so that multiple or groups of such cartridges can be stacked together to form a compact cartridge group. FIG. 56 is a rear perspective view of a cartridge group 176 including multiple individual cartridges 178a-d stacked wide side to wide side. Each cartridge 178a-d has one or more cartridge actuation ports 180 located on the narrow sides of the cartridge in first plate space 182a-d, where the actuation ports face in the same direction so that the individual cartridges of the cartridge group can be plugged into the corresponding connectors or receptacle ports of the receiver assembly that correspond to the individual cartridges, which are positioned adjacent to each other and connected, mounted, or attached to the pressure distribution manifold.

[0109] The cartridges of the cartridge group can be arranged in contact with each other, whether or not the cartridges are fused or adhered to each other. Alternatively, the cartridges can be loosely or at a certain spacing disposed adjacent to each other so that each cartridge in a group of cartridges can be individually inserted into and removed from the corresponding receiver assembly of each cartridge without interfering with the adjacent cartridges. This allows the individual cartridges to be disposed on a guide or track so that the actuation ports of the individual cartridges can be properly aligned with the corresponding connectors or receptacles of the individual cartridges and so that the individual cartridges can be more easily inserted and removed. The cartridge receiver assemblies can be positioned adjacent to each other to provide a compact cartridge group in space. Optionally, the cartridge receiver assemblies can be located within a single housing, which can provide alignment and insertion / removal tracks for the individual cartridges. Alternatively, each cartridge receiver assembly can be included in a separate housing for the same purpose. In settings where an array of subjects is provided with individualized fluid circulation, this arrangement allows individual cartridges to be swapped out with cartridges having different features (with respect to the number and distribution of pump and valve stations and the liquid flow path). Thus, the cartridge group configuration allows the cartridges to be conveniently and quickly adapted to the needs of their associated subjects when the fluid circulation requirements of any individual subject change. Furthermore, adjacent cartridges of the cartridge group can be interconnected via the respective liquid ports of the adjacent cartridges by means of, for example, a cross-over line. In this way, complex liquid mixing procedures can be performed when it is necessary to provide a subject with a solution having a particular component at a particular concentration. Thus, one or more cartridges of the cartridge group can be dedicated to a single subject as needed.

[0110] FIG. 57 is FIG. 56a front perspective view of a cassette set 176. In this example, for ease of illustration, cassette liquid ports 184 are located on the narrow side of each cassette 178a-d opposite the narrow side of the actuation port 180. While the actuation ports are preferably aligned on the same corresponding edge of the cassettes (so that a pressure delivery manifold can be positioned behind the cassette set), the liquid ports of the individual cassettes need not all be positioned along the same edge of the cassettes. In this embodiment, the cassette liquid ports 184 are positioned within the second inter-plate space 186a-d of the respective cassettes 178a-d. Thus, the cassette set 176 can be oriented so that the cassette set 176 faces outward from one or more receiver assemblies (not shown) to which the pressure distribution manifold is connected, mounted, or attached. Each cassette 178a-d is capable of providing liquid circulation to a separate subject, so that the number of individual cassettes in a set of cassettes can match the equal number of subjects that require liquid circulation. For example, a plurality of biological cell stations, tissues, or organs arranged for growth, experimentation, or testing can be supplied with circulating liquid, pharmaceuticals, nutrients, or other chemicals by a plurality of cassettes in a cassette set, each cassette potentially providing each cell station, tissue station, or organ station with a liquid solution having similar components or different components. A cassette set such as the cassette set 176 can also be configured to function as a solution mixing station, where the liquid output of one cassette of the set provides the liquid input of an adjacent cassette in the set, thereby allowing complex solution mixing schemes. As such, two or more cassettes can be reconfigured to serve a single subject.

[0111] FIG. 29 A rear perspective view of a cassette set 186 including dual-purpose intermediate plate cassettes 188a-d is shown, and FIG. 30 A front perspective view of the cassette set 186 is shown. In other embodiments, a cassette set can include one, two, or more dual-purpose intermediate plate cassettes and one or more single-purpose intermediate plate cassettes. In such a case, representative second inter-plate space 182a-d actuation ports 190 and representative first inter-plate space 186a-d liquid ports 192 are shown. Depending on the number and size of the individual pump stations and valve stations in the cassettes 188a-d, the use of dual-purpose intermediate plate cassettes can permit a greater density of multifunctional valve stations and pump stations to be housed in a relatively limited space.

[0112] In some applications, the stroke volume of the pump or other type of chamber, or the volume of the liquid chamber, exceeds the volume that the onboard pump or chamber can accommodate. In this case, an external pump pod or external chamber pod is used and positioned between two boxes. Liquid lines and / or actuation lines originate from opposite faces of the two boxes to supply the external pump or external chamber, thereby allowing liquid to flow, for example, from the first box to the external pod and then to the second box, each box housing an upstream or downstream valve station to control the flow of liquid. Alternatively, the external pump actuation line may originate from the face of the first box, while the liquid inlet and outlet lines may originate from the opposite second box. This type of box assembly also allows liquid lines to connect directly from one face of a box to the face of the opposite box. In previous implementations, such as FIG. 32 As shown, the opposing faces of boxes 194, 196, and 198 also include an actuation port 200 for an onboard pump station and an actuation port 202 for a valve station, as well as a liquid port 204, and liquid lines 206 and actuation lines 208 leading to an external pump 210 or an external chamber 212. This arrangement results in numerous flexible tubing connections for both the liquid lines and actuation lines inserted into the inner faces of the boxes, posing challenges to manufacturing, assembly, and maintenance.

[0113] FIG. 45 A conventional cartridge assembly is shown, in which a pneumatic actuation line 214 extends from an actuation port 216 on the cartridge face 218 to block connectors 220a, 220b for subsequent connection to a pressure distribution manifold for operating the cartridge assembly. This also includes a fluid line 222 extending from a fluid port 224 on each cartridge. This type of cartridge assembly has been significantly improved by incorporating the cartridge design of this disclosure.

[0114] FIG. 52

[0115] FIGS. 56-58 An example of box component 226 is shown, which performs the same as... FIG. 56 , FIG. 30 and FIG. 31 The existing box components have essentially similar liquid handling capabilities, and FIGS. 57-59 The cassette used to illustrate how the present disclosure significantly improves the structure, assembly, and maintenance of such cassette assemblies. In this example, the cassette assembly 226 shown is used for mixing, processing, and moving dialysate solutions in a portable hemodialysis device. However, the applications of this type of cassette or cassette assembly (i.e., a cassette having edge-mounted actuation ports and actuation channels extending between plates and parallel to the cassette surface) are not limited to hemodialysis systems. FIG. 56As shown, three boxes 228, 230, and 232 are connected together via fluid handling pods 234 and 236. These inter-box pods may include self-contained diaphragm pumps with both actuation conduits and fluid conduits, or other liquid-carrying chambers 236 with only fluid conduits. Examples of other types of liquid-carrying pods include fluid mixing chambers or fluid balancing pods, in which flow through a first fluid line is balanced with flow through a second fluid line via a pod having a first variable volume separated by a flexible diaphragm and a second variable volume. Each fluid handling pod 234, 236 is fluidly connected to one or two boxes located on the side of the fluid handling pod 234, 236 via a flexible or rigid conduit. A rigid liquid conduit 238 may be preferred because it can provide structural support for the box assembly. In the case of the diaphragm pump pod 234, both the liquid-carrying conduit and the actuation conduit may extend to one or two boxes located on the side of the liquid-carrying conduit and the actuation conduit. The conduit 238 penetrates the surface of the side box to reach a fluid passage or actuation passage located in a first or second inter-plate space of the box. Typically, the actuation passage driving the inter-box pump pod is guided uninterruptedly from the box actuation port to the actuation chamber of the pump pod. The fluid passage of the inter-box pump pod or another type of fluid handling pod is connected via one or more diaphragm valves located in the box to corresponding inter-plate fluid passages in one or both side boxes. The actuation passages of these diaphragm valves, the actuation passage for the pump pod, and any other actuation passages in the box travel within the first or second inter-plate space of each box to the first edge of the respective box, terminating at the box actuation port 240. In the box assembly, each box 228, 230, 232 has an actuation port 240 located on the narrow side or edge of the respective box, and each box 228, 230, 232 is configured to face the same direction such that the box assembly actuation port occupies one side of the box assembly. This allows the cartridge assembly 226 to be inserted into or removed from one or more receiving assemblies with a single action. This arrangement eliminates the need for a flexible conduit to connect the cartridge actuation port to the corresponding manifold output port. FIG. 57 In the example shown, box 228 is optionally configured as a single-purpose intermediate plate box (in which all actuation ports are located in a first inter-plate space or a second inter-plate space). In the same example, boxes 230 and 232 are optionally configured as dual-purpose intermediate plate boxes, wherein some actuation ports are located in two inter-plate spaces on either side of box intermediate plates 242, 244. Of course, other arrangements are possible depending on the fluid handling tasks required for the box assemblies organized in a similar manner.

[0116] FIG. 59 Depicting FIG. 23FIG. 22 is a partial exploded view of an example cartridge assembly 226 shown in FIG. 21. Assembled cartridges 228, 230, and 232 and intervening pump 234 or other liquid-carrying chamber 236 are held in the frame assembly to ensure proper alignment of the cartridge ports during installation and operation. Previously disclosed cartridge assemblies can rely on rigid conduits (e.g., conduit 238) and a few retaining rods or springs to hold the assembly together (see, e.g., U.S. Patent No. 8,815,001, the disclosure of which is incorporated herein by reference), but do not require actuation ports for precise alignment for direct insertion into a manifold assembly. In the presently disclosed cartridge assemblies, the carrier frames 505 and / or 507 can eliminate this problem by compactly securing the cartridge assembly 226 and holding the cartridge assembly 226 in the desired configuration or alignment. FIG. 45 FIG. 22 is a partial exploded view of an example cartridge assembly 226 shown in FIG. 21. Assembled cartridges 228, 230, and 232 and intervening pump 234 or other liquid-carrying chamber 236 are held in the frame assembly to ensure proper alignment of the cartridge ports during installation and operation. Previously disclosed cartridge assemblies can rely on rigid conduits (e.g., conduit 238) and a few retaining rods or springs to hold the assembly together (see, e.g., U.S. Patent No. 8,815,001, the disclosure of which is incorporated herein by reference), but do not require actuation ports for precise alignment for direct insertion into a manifold assembly. In the presently disclosed cartridge assemblies, the carrier frames 505 and / or 507 can eliminate this problem by compactly securing the cartridge assembly 226 and holding the cartridge assembly 226 in the desired configuration or alignment. FIG. 46 ​ The example embodiments in FIGS. 21 and 22 show a first carrier frame 505 and a second carrier frame 507 that can engage the cartridge assembly 226 from opposite directions. Some embodiments can provide similar carrier frames to secure the cartridge assembly 226 from adjacent sides. Other embodiments can also provide a unitary carrier frame to secure the cartridge from more than one pair of opposite sides.

[0117] ​The carrier frames 505 and 507 can also include plate rails that can slide on the corresponding cartridge plates of the cartridges 228, 230, and 232 for engagement with the cartridge assembly 226. Joining the frame components together and securing the enclosed cartridge plates in the rails can eliminate the need for holes or drilled holes on any of the three cartridge plates to secure the three cartridge plates to the frame. The rail configuration, and the absence of screws, nuts, or clips through the cartridge plates, can reduce the likelihood of damaging the cartridge assembly and interfering with any pneumatic connections or passages in the cartridge assembly. For example, the first carrier plate 505 can include a first set of plate rails 505A, 505B, and 505C, and the second carrier plate 507 can include a second set of plate rails 507A, 507B, and 507C. The plate rails 505A, 505B, 505C, 507A, 507B, and 507C can include elongated slots capable of partially or completely receiving at least one edge or a portion of an edge of the corresponding cartridge plate of the cartridges 228, 230, and 232. For example, with reference to the first carrier frame 505, the plate rails 505A, 505B, and 505C can receive the edges of the cartridge plates of the cartridges 228, 230, and 232, respectively. In embodiments, the rails can include a cover feature. For example, the rails 505A and 505C of the first frame 505 can include cover features 505F and 505G positioned on the ends of the respective rails. The plate rails 507A, 507B, and 507C can be engaged with the cartridge assembly 226 by receiving the edges of the corresponding cartridges 228, 230, and 232. Further, the walls of the plate rails 505A, 505B, 505C, 507A, 507B, and 507C can also optionally include notches 506 configured to receive and support the corresponding rigid liquid conduit 238 when the carrier frames 505, 507 are engaged with the cartridge assembly 226. The plate rails 505A, 505C, 507A, and 507D can have closed ends and open ends. The open ends of the rails can be included to avoid interference with the nearby cartridge ports 240. It should be noted that the first carrier frame 505 and the second carrier frame 507 can slide onto the respective cartridge edges to engage with the cartridge assembly 226, and the first carrier frame 505 and the second carrier frame 507 can not require additional fastening devices to directly engage with the cartridges 228, 230, and 232. Further, the securing features of the auxiliary rails, such as but not limited to the cover features 505F, 505G, and the notches 506 and 508, can further strengthen the engagement between the cartridge assembly and the frame, thus allowing any forces exerted on the frame to be more evenly distributed on the cartridge assembly, and potentially avoiding twisting or distorting the cartridge assembly 226. This arrangement can help to compactly install the cartridge assembly 226 and remove the cartridge assembly 226 from the array of manifold receptacles of the hemodialysis apparatus 246 without causing deformation of the cartridge assembly, and thus misalignment of the cartridge ports.

[0118] The plate rails 505A, 505B, 505C can be interconnected by upper and lower bars 505D, 505E that extend perpendicular to the plate rails. The lower bars 505E interconnect the plate rail 505A with the plate rail 505B and the plate rail 505B with the plate rail 505C at the open end of the rails and near the cartridge ports 240. The upper bars 505D interconnect the plate rail 505A with the plate rail 505B and the plate rail 505B with the plate rail 505C at the closed end of the rails. Similarly, the rails 507A, 507B, 507C are interconnected by upper and lower bars 507D, 507E that extend perpendicular to the plate rails. The lower bars 507E interconnect the plate rail 507A with the plate rail 507B and the plate rail 507B with the plate rail 507C at the open end of the rails and near the cartridge ports 240. The upper bars 507D interconnect the plate rail 507A with the plate rail 507B and the plate rail 507B with the plate rail 507C at the closed end of the rails.

[0119] At least one cross bar 511 can be positioned to connect the first and second carrier frames 505, 507 when the frame is positioned in engagement with the cartridge assembly 226. In this example, the cross bar 511 is disposed longitudinally through the cartridge assembly 226 and the cross bar 511 connects the first and second carrier frames 505, 507 at opposite ends of the cross bar. This arrangement helps to stabilize the sides of the frames 505, 507 near the ports 240 of the cartridges 228, 230, 232. The cross bar 511 helps to prevent the frames 505, 507 from shifting position relative to the cartridge assembly 226. The connection between the respective ends of the cross bar 511 and the corresponding carrier frames 505, 507 can be established by fastening features such as, but not limited to, screws, bolts, adhesives, laser or ultrasonic welding, or other similar fastening mechanisms. Alternatively, the cartridge assembly 226 can provide alternative or additional connection elements between the first and second carrier frames 505, 507 to secure the first and second carrier frames 505, 507 to each other and to the cartridge assembly 226, including but not limited to clips similar to the clips 512 in FIG. 5, threaded rods, zip ties, or other elements that limit the extent to which the frames 505, 507 can shift relative to each other. ​

[0120] ​ ​ ​​A first support plate 513 and a second support plate 515 are also depicted. The first support plate 513 can be arranged to interconnect the first and second carrier frames 505, 507 when they are engaged with the cartridge assembly 226. In the present example, the first support plate 513 is positioned on a side of the cartridge assembly 226 that is perpendicular to the side on which the first and second carrier frames 505, 507 are positioned. Further, the first support plate 513 is positioned on a side of the carrier frames opposite the cartridge ports 240. The first support plate 513 can additionally include flanges 513A and 513B on opposite edges. These flanges 513A, 513B can be configured to engage the upper bars 505D of the first carrier frame 505 and the upper bars 507D of the second carrier frame 507. The first support plate 513 can be mechanically secured to the upper bars 505D, 507D by clips, screws, or the support plate 513 can be bonded to the upper bars 505D, 507D. Alternatively, the upper plate 513 and at least one of the frames 505, 507 can be molded together. The first support plate 513 can engage the upper bars 505D, 507D when the carrier frames have been engaged with the edges of the cartridges 228, 230, 232 of the cartridge assembly 226. Thus, the first support plate 513 and the crossbar 511 can secure the first and second carrier frames 505, 507 to one another during engagement with the cartridge assembly 226. The assembly including the carrier frames 505, 507, the crossbar 511, and the first support plate securely holds the cartridge assembly 226 and helps to more evenly distribute external mechanical forces to the cartridge assembly components to avoid distorting the relative positions of the cartridge assembly components.

[0121] The first support plate 513 can also provide an inner surface 513D (see ​ and ​ ) facing the cartridge assembly 226 and an opposite outer surface 513C facing away from the cartridge assembly 226. During installation of the cartridge assembly 226, the outer surface 513C of the first support plate 513 can interface with a cartridge loading device (not shown) described below. The inner surface 513D and the outer surface 513C provide surfaces to which the cartridge loading device can apply forces to move the cartridge assembly as a unit. The first support plate 513 can also provide alignment features to properly load and seat the cartridge assembly 226 in the loading device.

[0122] ​A second support plate 515 is also shown, which can optionally be included in engagement with one of the carrier frames 505, 507 to minimize torsion or flexing of the frame. In the present example, the second support plate 515 is mounted to the second carrier frame 507, and the second support plate 515 is attached to the frame by connection elements 519. The connection can be achieved by receiving the connection elements 519 into corresponding connection joints 520 provided on the second carrier frame 507. In another implementation, the second carrier frame 507 can be integrally combined with a support plate such as, but not limited to, the second support plate 515 as a single component. Flexing or torsion of the first carrier frame 505 can also be reduced by including diagonal cross members 523. The cross members 523 can be integral with the structure of the second carrier frame 505, or the cross members 523 can be separately attached to the frame. Additional support elements similar to the support plates 513, 515 and support brackets 523 can be provided to assist the carrier frames 505, 507 and maintain the desired arrangement of the cassette assembly 226.

[0123] ​ and ​ A perspective view of an exemplary first support plate 513 is depicted. The flanges 513A and 513B can also provide engagement features such as, but not limited to, resilient clips or grips 514. The first support plate 513 can also include one or more clips 514 on the non-flanged side. The clips 514 can be configured to engage the edges of the carrier frames 505 and 507. For example, the clips 514 can be configured to engage the upper bars 505D, 507D. Alignment elements such as one or more tabs 516 ​ ) can be included on the edges of the carrier frames 505, 507. The tabs 516 can serve as alignment features for the slots 514B on the first support plate 513 to ensure proper alignment and connection between the first support plate 513 and the carrier frames 505, 507. In the present example, the first support plate 513 can include longitudinal and / or lateral stiffeners 517 to reduce mechanically induced deformation of the first support plate 513.

[0124] ​ A hemodialysis apparatus 246 configured to enclose the cassette assembly 226 is shown. The front panel 248 is configured to include dialyzer recess and retention portions 250, a blood pump cassette receiving assembly 252, and the front panel 248 is configured to retain a blood tubing set (not shown). The dialysate cassette assembly 226 is configured to be housed within the enclosure of the apparatus 246 behind the front panel 248.

[0125] ​ A hemodialysis apparatus 246 configured to enclose the cassette assembly 226 is shown. The front panel 248 is configured to include dialyzer recess and retention portions 250, a blood pump cassette receiving assembly 252, and the front panel 248 is configured to retain a blood tubing set (not shown). The dialysate cassette assembly 226 is configured to be housed within the enclosure of the apparatus 246 behind the front panel 248. ​The enclosure or housing 254 of the apparatus 246, with the front panel 248 and other components removed. The interior configuration of the enclosure 254 allows the cartridge assembly 226 to be positioned above an interior shelf 256 of the enclosure 254. The interior of the enclosure 254, e.g., below the shelf 256, is arranged to hold other components such as a heater for the dialysate solution, tubing for various liquid flow paths, a dialysate reservoir or tank, and one or more devices to detect the electrical conductivity and temperature of the dialysate solution at various stages of mixing. Behind this enclosure 254 is a recess 258 arranged to hold a pressure distribution manifold (in this case a pneumatically actuated manifold) having electromechanical valves and one or more electronic controllers, at least one of which is configured to control the electromechanical valves of the manifold. These components are positioned outside of the enclosure 254 to help protect them from high temperatures that can be used in sterilizing the liquid-carrying components of the hemodialysis apparatus 246. ​ A rear perspective view of the enclosure 254 is shown, highlighting the recess 258 directly below the shelf 256 of the enclosure 254. Thus, the pressure distribution manifold can be positioned directly below the cartridge assembly 226, which is within the enclosure 254, while the pressure distribution manifold is outside of the enclosure 254.

[0126] ​

[0127] ​ and ​ The mounting and retention of the cartridge assembly 226 in the enclosure 254 is depicted. In ​ the cartridge assembly 226 is raised to be directly above the three cartridge-receiving assembly, with the three arrays of cartridge actuation ports 240 aligned with their respective receiving port on the adapters 266, 268, 270. The receiving assembly is configured to adapt the actuation port arrays of the cartridge assembly 226 with the actuation outlet of the pressure distribution manifold that is outside of the enclosure and below the shelf 256. Lowering the cartridge assembly 226 allows the cartridge actuation ports 240 to engage with their respective adapters by a press-fit connection. Sealing of the individual actuation ports 240 can be achieved by the use of O-rings or gasket with elastomeric wiper seals or other means commonly used to seal press-fit connections. The adapters in turn can provide a direct connection to the output ports of the pressure distribution manifold ​ below the shelf 256 and outside of the enclosure 254. ​ A cartridge loading device 292 is also depicted that can receive the cartridge assembly 226 and hold it in place during installation. A handle 308 belonging to the loading device 292 can be manipulated to lock the cartridge assembly within the enclosure 254. Reference is made to the following figures.​ A detailed description of the operation of the device 292 and handle 308 to lock and retain the cartridge assembly is provided. In one configuration, ​ The loading assembly can be in an open position that depicts the operation handle extending parallel and away from the cartridge assembly. ​ Depicts the locking of the cartridge assembly 226 in the cartridge receiving space by indicating the operation handle 308 to be angled downward, moving the loading means towards the receiving assembly of the manifold, and thus pressing the cartridge assembly 226 into and securing the cartridge assembly 226 in the corresponding adapter port. In the present example, the loading means 292 can comprise force applying elements, such as but not limited to one or more levers that can interface with the first support plate 513( ​ and ​ ) and can be operated by the handle 308. Lowering the handle 308 can allow the force applying elements to push on the first support plate 513. The force can be transmitted through the cartridge frame 505, 507 to the cartridge assembly 226, wherein the frame presses the cartridge assembly 226 towards the adapters 266, 268 and 270. ​ Depicts the cartridge assembly 226 in an operative configuration, i.e. the cartridge assembly 226 is pressed such that the array of cartridge actuation ports 240 is aligned with the respective adapters 266, 268 and 270 of the cartridge actuation ports 240. It should be noted that, ​ The handle 308 in

[0128] ​ 、 ​ The embodiment of the hemodialysis device 246 shown in ​ includes an enclosure 254 in which the footprint of the cartridge assembly 226 extends and overhangs the shelf 256 in a forward direction from the shelf 256. To this end, a set of manifold interfaces or adapters 266, 268, 270 are configured to extend in a forward direction from the shelf 256, as shown in ​ The adapters 266, 268 and 270 provide the necessary mating of the cartridge assembly 226 actuation ports 240 with their respective connectors or receiving ports 272 located on the interfaces or adapters 266, 268, 270. In the example, the adapters 266, 268, 270 serve as receiving assemblies, providing an array of receiving ports for mating with the cartridge ports 240 arranged in each cartridge 228, 230 and 232, respectively.A bottom perspective view of the enclosure 254 is shown with the interfaces / adapters 266, 268, 270 installed. In this view, the extent to which the adapters protrude out of the enclosure shelf 256 (and thus also out of the pressure delivery manifold 260) is evident. The adapters 266, 268, 270 serve to map the box ports, which are arranged in an extended direction along the edges of the respective cartridges, to a more spatially compact array of manifold ports in the risers or top blocks 276A-C between the adapters 266, 268, 270 and the upper block 274 of the underlying pressure distribution manifold 272.

[0129] ​

[0130] ​ A schematic view of an embodiment of a pressure distribution manifold (or manifold assembly) is shown. The manifold assembly is arranged to selectively provide pneumatic pressure (positive, negative, or atmospheric) to control pneumatically driven pumps and / or valves on two independent pump cartridges. In this improved embodiment, a first set of pneumatic outlets is configured for direct connection (i.e., direct plug-in connection) with a first pump cartridge or cartridge assembly (i.e., with the manifold assembly or with an adapter directly connected to the manifold assembly). In embodiments, the direct connection interface is schematically illustrated as one or more risers or "top blocks" 276A, 276B positioned on the upper side of the manifold assembly 260. The top blocks include direct connection ports 261 configured to directly connect with a first pump cartridge (not shown), which can be positioned directly above the manifold assembly 260. The manifold or manifold assembly also includes a second set of pneumatic outlets configured for indirect connection to a second pump cartridge via a flexible or malleable tube. In ​ An exemplary fitting 582 for indirect connection to a second pump cartridge (not shown) is also shown in the middle, which connection is configured for a flexible or malleable tube to travel a distance away from the manifold assembly 260 to a remotely located second pump cartridge. In the context of the presently described hemodialysis apparatus, a dialysate cartridge assembly can be configured to plug directly into the manifold assembly via ports 261, and a blood pump cartridge assembly (more remotely located on the front panel of the dialysis device) can be configured for pneumatic connection to the manifold assembly via a flexible or malleable tube to a plurality of fittings (here represented by exemplary fitting 582).

[0131] ​ Another improvement in the manifold assembly 260 is also shown, which helps to prevent or reduce the accumulation of particulate or liquid debris on the internal sealing surfaces of the electromechanical pneumatic control valves. An exemplary valve 267 is shown in a generally horizontal orientation. Any internal valve seats or sealing surfaces are oriented to avoid having horizontal surfaces that can accumulate debris. In ​In the illustrated diagram, the lower or bottom manifold block 272 cooperates with the middle manifold block 274. The lower manifold block 272 has a "T" shaped cross section (across the long axis "Z" of the manifold assembly 260), and includes a horizontal portion 272A and a lower pendant portion 272B on which are disposed a plurality of valve mounting surfaces and openings. An exemplary valve 267 is shown mounted to one such surface and on one such opening. A valve face seal (not shown) is assumed to interface the valve body with the mounting surface of the pendant portion of the manifold. For convenience, the pendant portion 272B is shown as having a vertical orientation with respect to the horizontal portion 272A. The pendant portion 272B can also have a non-vertical orientation, such as can have a non-vertical orientation in which the valve mounting surfaces and openings are angled in an upward direction, which orients the valve body and face seal in a downward angled direction. Such angled orientation would also help to prevent the accumulation of liquid (e.g., liquid condensate) or debris on valve components (e.g., valve seats) having sealing surfaces. In many, but not all, valve implementations, the associated internal valve plunger or piston will operate in a horizontal or near horizontal direction, which is indicated by the horizontal orientation of the valve body in the illustrated diagram. ​ The valve 267 is schematically illustrated in the middle.

[0132] In the example shown in the middle, ​ In the example shown in the middle, the pressure source lines 263 are shown as embedded within the lower or bottom manifold block 272. Depending on how the internal pneumatic passages in the manifold assembly 260 are oriented, these source lines can also be located in the middle block 274. In the illustrated diagram, each of the plurality of valves 267 receives an input line from one of the pressure source lines 263, and each of the plurality of valves 267 has an output line that is ultimately connected to an output port of the manifold assembly - either a direct connection port 261 or an indirect connection port 582.

[0133] ​ A diagram is shown of an embodiment of the manifold assembly 260 in which the direct connection blocks 276A, 276B project, are suspended or offset with respect to the main body of the manifold assembly. In this illustration, the long axis ("Z") of the manifold assembly can be considered to accommodate a pump cassette of arbitrary length in the long axis direction. However, if the pump cassette is configured to also have an array of inlet ports that exceed the primary front-to-back ("X") dimension of the manifold assembly, then the direct connection blocks can be arranged to project the manifold assembly in that direction. The ports 261 can then be connected to passages within the blocks 276A, 276B to lay out a more compact array of one-to-one mapped ports on the top of the middle block 274.

[0134] ​A schematic view of an embodiment of a manifold assembly 260 is shown in which an array of pressure sensor ports 567 is positioned between direct connection blocks 276A and 276B. In this case, various pneumatic channels within the manifold assembly can have branch or line connections to the sensor ports 567A of the pressure sensor array 567. In most, but not all cases, these channels are connected to the output lines of pneumatic control valves and to the output ports of the manifold assembly that are connected to the valve output lines. In an example, the array of pressure sensing ports can be configured to mate with a printed circuit board (PCB) positioned above the array and including a corresponding array of pressure sensors. The pressure sensors of the PCB can be connected to a hemodialysis controller that uses the pressure information to control the pneumatic control valves to deliver a predetermined level and predetermined pattern of pressure to the pump or valve objects in the connected pump cassette.

[0135] ​A schematic view of an embodiment of a manifold assembly 260 is shown, which includes one or more manifold adapters or interface blocks 266, 268. In this example, top blocks 276A, 276B are used as risers to provide spacing between the mounted direct connect pump cartridges and the main body of the manifold assembly 260. The risers can include pneumatic passages that connect a plurality of valves (such as valve 267) on the manifold to the manifold adapters or interface blocks 266, 268 for eventual connection to the associated pump cartridges. The manifold adapters or interface blocks can be configured to spatially redistribute the output ports 261a, which are relatively closely spaced in the manifold's riser blocks or other blocks, into a differently spaced array or distribution of output ports 261b. In this way, the direct connect output ports of the manifold assembly can be spatially arranged or redistributed to match the corresponding input ports of a mating direct connect pump cartridge assembly. Thus, the manifold adapters 266, 268 include transfer ports on a first side facing and mating with the manifold 274 or its associated riser 276A, 276B that map into corresponding transfer ports 261b on an opposite second side facing and mating with the pump cartridge assembly. Thus, a first array of manifold output ports having a first spatial port configuration can be directly mated with a second array of cartridge input ports having a second spatial port configuration. The mapping between the corresponding transfer ports is achieved by the layout of internal passages within the manifold adapters 266, 268. In this case, the spatial array of manifold output ports or riser output ports has a length that is less than the length of the spatial array of manifold adapter transfer ports on the second side of the adapter. The result is that the manifold adapter overhangs the front side of the manifold. These features help to decouple the spatial and dimensional constraints of the pump cartridge assembly from the spatial and dimensional constraints of the manifold assembly configured to drive one or more cartridges in the cartridge assembly. In the current embodiment, the manifold assembly can be made as compact as the valve, passage, and port constraints permit, while retaining the ability to interface with pump cartridges that can have very different spatial constraints or spatial array requirements for their actuation ports.

[0136] ​ 、 ​Details of one embodiment of a pneumatic actuation manifold in the form of a pressure distribution module 260 are shown. The pressure distribution module 260 provides selectable pneumatic connections from a plurality of pressure sources to cartridge assemblies received in ports on platforms plugged to manifold adapters 266, 268, 270. The pressure distribution module 260 can also provide selectable pneumatic connections to remote cartridges via flexible pneumatic lines or extensible pneumatic lines (not shown). The pneumatic connections are selectively controlled by digital or binary pneumatic valves 262, 265, 267 mounted in or on the manifold block. One or more controllers control the state of the valves based on signals received from pressure sensors mounted on an upper block 276, and in the case of a hemodialysis apparatus, the one or more controllers provide programmed instructions to selectively actuate the valves and pump blood, dialysate, and water to provide a dialysis treatment to a patient.

[0137] The pressure distribution module 260 controls the action of pneumatically driven diaphragm pumps and pneumatically driven liquid valves by selectively connecting to one or more pressure reservoirs via digital or binary electromechanical valves. The electromechanical valves can include two-way digital valves or three-way digital valves. Digital valves can have two positions. Two-way digital valves are either open or closed. Three-way digital valves connect a common port to either a first port or a second port. One or more controllers control the state of the valves 262, 265, 267 based in part on signals received by the one or more controllers from pressure sensors 565 (see ​ ) mounted on the pressure distribution module 260. The pressure reservoirs can include high positive pressure reservoirs, low positive pressure reservoirs, negative pressure or vacuum reservoirs, and vents to atmosphere.

[0138] The pressure distribution module 260 can be assembled from a plurality of manifold blocks. ​ 、 ​ The pressure distribution manifold 260 in FIG. 6 includes a T-shaped manifold block 272, an intermediate manifold block 274, and an end manifold block 276. The pressure distribution manifold 260 also includes a plug-in valve 265 mounted in the intermediate manifold block 274 and surface mount valves 267 mounted on the vertical legs of the T-shaped manifold block 272. The arrangement of pressure reservoir ports 263, a first set of valves 265, and a second set of valves 267 can be horizontal with respect to the faces 272F, 274F, and 276F ​ ) of the manifold blocks 272, 274, and 276, respectively. This arrangement can help avoid the accumulation of debris or liquid in the valves that can potentially impair the function of the valves or shorten the maintenance-free life of the valves. Pressure sensors 565 ​ ) are mounted to ports 567 on the upwardly facing surfaces of the end manifold block 276. The adapters 266, 268, and 270 provide ports 266P, 268P, 270P to receive the ports 240 of the cartridge assemblies 226.

[0139] Intermediate manifold 274 and T-manifold 272 may include internal supply lines for atmospheric pressure, low positive pressure, high positive pressure, and negative pressure. One or more of these internal supply lines extend through the length of manifold 272, 274. Port 264 for the internal supply lines is capped or has port 263 for flexible tubing connection to a pressure reservoir. Both end faces of manifold 272, 274 may include ports for connecting internal supply lines (not shown) to an external pressure reservoir.

[0140] Multiple diaphragm pumps and diaphragm valves can be grouped together as follows: ​ The single box shown. Multiple such boxes can be connected together to form a shape like... ​ , ​ The cassette assembly 226 is shown. In this configuration, the assembly spaces the cassettes to accommodate an external pump, mixing chamber, or fluid balancing chamber having a volume larger than that that could be accommodated within any of the individual cassettes. The pressure distribution module 260 includes adapters 266, 268, and 270 extending at right angles to the long axes of manifold blocks 272, 274, and 276. The adapters extend the interface area of ​​the pressure distribution module from the coverage area of ​​the manifold blocks and the riser to any area required to receive the port 240 of the cassette assembly 226. The pneumatic layout and port distribution on and within adapters 270, 268, and 266 and their sub-components (not shown) allow for direct connection between the cassette assembly 226 and the manifold blocks 272, 274, and 276, wherein each port of the cassette assembly is mapped one-to-one to a corresponding actuation port of the manifold assembly.

[0141] An external pressure reservoir—which the pressure distribution module 260 can be connected to—can be maintained at a specified or predetermined pressure by a pump controlled by the system controller. In an embodiment, the high-pressure reservoir can be maintained at approximately 1050 mmHg, and the positive-pressure reservoir can be maintained at approximately 800 mmHg. The actual pressure delivered to various pneumatically actuated pumps and valves can vary based on the pressure reservoirs terminated with two-way and three-way valves on the pressure distribution module 260. Furthermore, intermediate pressures can also be transmitted via a combination of rapid opening and closing of switching valves. Typically, a high-pressure source can be used to actuate diaphragm valves to ensure leak-free and reliable valve closure during operation of the cartridge assembly.

[0142] ​An exploded view of the pressure distribution manifold 226 is depicted. The manifold blocks 272, 274, and 276 can also include intermediate elements that connect features in each of the manifold blocks 272, 274, and 276. These intermediate elements and connecting features can facilitate assembly of the three manifold blocks and establish pneumatic connections between the individual manifold blocks 272, 274, and 276. A first set of intermediate components can include, for example, a first plate 550, a first gasket 552, and a second gasket 554 that can be used between the T-shaped manifold block 272 and the intermediate manifold block 274, and a second set of intermediate components can include a second gasket plate 555, a third gasket 556, and a fourth gasket 558 positioned between the intermediate manifold block 274 and the end manifold block 276. Two manifold blocks 272, 274 can be clamped together with a gasketed intermediate plate 550 between the two manifold blocks 272, 274. The intermediate plate 550 can also be referred to as a back plate because the intermediate plate 550 provides a rigid surface that forces the gaskets to seal against a plurality of channels that can be provided on the end manifold block 276, the T-shaped manifold block 272, and the intermediate manifold block 274.2Each manifold block 276, 274, 272 can include at least one face 276G, 274F, 272F (see ​ 、 ​ 、 ​ ) having channels and various ports that mate with ported plates and gaskets such as the plates 550, 555 and gaskets 552, 554, 556, 558. The respective channels can be configured as grooves that include a solid bottom and two sidewalls and an open top. The channels can be cut into one face 276F, 274F, 272F of the manifold block, or the channels can be formed with walls that extend above the surface of the manifold block face 276F, 274F, 274G, and 272F. As shown in ​ the open top of the channel can be sealed by clamping a gasket 554, 552, 556, 558 backed by a rigid flat intermediate plate 550, 555 against the channel. In one example, the intermediate plate 550 is a back plate that forces the gasket 552 against all of the channels on face 272F and forces the gasket 554 against the channels on face 274G. It should be noted that in ​In this embodiment, face 274G is opposite face 274F. The manifold blocks and gaskets can include features to ensure that pressure is distributed substantially evenly across the gaskets. The intermediate plates 550 provide a generally smooth and rigid backing for the gaskets, such that more than one manifold block can be assembled or clamped into a multi-part pneumatic manifold 260. The channels are connected to pressure sources, valves, sensors, and outlet ports that reside on other faces of the blocks. The manifold blocks 276, 274, 272 can be clamped together by mechanical fasteners 570 that clamp the gaskets 552, 554, 556, 558 and intermediate plates 550, 555 between the manifold blocks 276, 274, 272 to seal the plurality of channels on the channel-bearing faces 272F, 274F, 274G, 276G of each of the manifold blocks 272, 274, 276. This clamping arrangement allows for compact assembly of multiple manifold blocks with a set of channels on one face of each block 272, 274, 276.

[0143] The connection points of the T-shaped manifold block 272 can be configured to receive screws that extend through other components that assemble the pressure distribution manifold 260 into a unit. In this example, a matching connection point 572 can be provided on the first gasket plate 550, a connection point 573 on the intermediate manifold block 274, and connection points 573 on the third gasket 556 and fourth gasket 558. The first set of valves 265 can operate on pneumatic passages within and / or connecting the manifold blocks 272, 274, and 276.

[0144] ​ and ​ An embodiment is shown that includes a plurality of plug valves 265 and connections to a pressure reservoir 263. The plug valves are inserted into manifold ports. Corresponding cavities (not shown) are formed to accommodate seals on the exterior of the plug valves 265. The machined cavities can have a set of dimensions defined by the manufacturer of the valves to ensure sealing and proper operation of the plug valves 265. In this particular embodiment, approximately forty-eight plug valves 265 are installed on a side of the intermediate manifold block 274. This side of the intermediate manifold block 274 is perpendicular to the channel-bearing face 274F. In some embodiments, the plug valves are three-way valves, such as Lee LHDA plug-in valves available from The Lee Company USA, Westbrook, Conn. The number of electromechanical valves is determined by the number of individual diaphragm pumps and valves that will be operated in the directly connected cartridge assemblies and the remotely connected cartridge assemblies, if desired, and the linear array of electromechanical valves forms the extended length of the manifold assembly.

[0145] Reference is now made to ​, the pressure distribution manifold can be used as a pneumatic actuation device for components other than the cassette assembly 226. For example, the pressure distribution manifold 260 can also be in pneumatic communication with other pneumatically actuated valves, diaphragm pumps, pneumatic cylinders, and remote cassette pneumatic including diaphragm valves and diaphragm pumps. In one example, the pressure distribution module 260 controls the position of the stopper 251 in ​ , which includes a pinch valve to block the blood line, and is driven by a pneumatic cylinder. In another example, the pressure distribution module 260 can be placed in pneumatic communication with the dialysate tank to use pressure information for tank volume measurement. In addition, the pressure distribution module 260 can be arranged to control the pumping action of a blood pump cassette (not shown) mounted on the blood pump cassette receiving assembly 252 in ​ ​ , the port 582 shown as located on the T-manifold block 272 can be connected directly to one or more blood pump cassettes or through a flexible or malleable tube to establish the required pneumatic connections. The port 582 includes a fitting that is connected to a pneumatic tube and can be removed from the T-manifold 272 individually. The pneumatic tube connected at one end to the port 582 can be connected at a second end to a connector on the surface of the wall 255( ​ ) of the dialysis machine. Then, a second connector inside the housing can use a flexible tube to form a connection with, for example, a dialysate tank, a pneumatically actuated tube stopper, and / or the blood pump cassette receiving assembly 252.

[0146] In this example, the plug-in valve 265 and the surface mount valve 267 control the pneumatic pressure delivered to the stoppers, blood pump cassettes, and other pneumatically actuated components in the hemodialysis machine 246. Mounting features such as the standoffs 580 can be provided to attach the pressure distribution module 260 to the back wall of the enclosure 254 and to set the position of the adapters 266, 268, 270 relative to the enclosure 254.

[0147] With continued reference to ​ , ​ ​Valves 267 disposed on the T-manifold block 272 are electro-mechanical valves that seal against a flat surface or a surface machined to accept the valve face. In some embodiments, the surface-mounted valves 267 can be proportional valves or continuously variable valves (also known as "variable valves"). In other embodiments, the surface-mounted valves 267 are binary two-way or three-way valves. In some examples, the surface 272F is generally horizontal, such that the legs of the T-shaped cross-section of the manifold 272 are generally vertical. In a preferred arrangement, the valve-mounting surface of the legs is vertical or slightly upwardly inclined, such that the ports on the valves 267 are horizontal or downwardly inclined to avoid the accumulation of debris or liquid. Sealing features such as O-rings and / or other elements can be provided on the valves to inhibit fluid or air leakage. These valves can be any digital two-way or three-way valve suitable for surface mounting, such as, for example, model 11-15-3-BV-12-P-0-0 from Parker Hannifin Corporation in Hollis, N.H.

[0148] Referring now to ​ The pneumatic flow on the pressure distribution manifold 226 can be monitored by one or more pressure sensors, which can be mounted on a sensor board (e.g., a PCB). In the present example, a sensor board 560 can be positioned above the surface 567 of the upper manifold block 276 in the space between the uprights 276A-C. Pressure sensors 565 can be mounted directly to the face 276F of the first end manifold block 276. The pressure sensors 565 can be integrated circuits soldered to a printed circuit board (PCB) 560. As ​As shown in FIG. 5, a printed circuit board 560 including one or more pressure sensors 565 can be mounted on a top face 276F of the second end manifold block 276 parallel to the channelled face with a grommet to pneumatically isolate each sensor and a plate (not shown) to hold the PCB 560 in place and compress the grommet sufficiently to seal each pressure sensor from the atmosphere. The sensor plate 560 can be coupled with the surface 567 of the end manifold block by fastening components such as screws, nut and bolt pairs, rivets, adhesives, or a combination of such fastening mechanisms. An example pressure sensor 565 can be obtained from Freescale Semiconductor, Inc. in Tempe, Ariz. (part number MPXH6250A). A PCB including multiple pressure sensors 565 can be mounted as a unit to the end manifold block 276. The pressure sensing face of each pressure sensor 565 can be fluidly connected to a desired pressure source such as a reference volume, or more distantly to an actuation chamber of a diaphragm pump, or to a dialysate reservoir tank. In some cases, the sensors are arranged to monitor liquid pressure in various diaphragm pumps of a liquid treatment cartridge. The end manifold block 276 provides risers 276A, 276B, and 276C that can interface with respective adapters 270, 268, and 266. The manifold assembly is configured so that the sensor plate 560 avoids interfering with the interface between the risers and the corresponding adapters. The risers also provide separation between the overlying liquid treatment cartridge assembly and the temperature sensitive sensor plate 560, allowing for the placement of an insulator 269A (e.g., see FIG. 5) therebetween. ​

[0149] ​ and ​ FIG. 5 illustrates a second manifold block 276 having a face 276F and a base surface 276G. The base surface 276G can be configured to cooperate with one or more intermediate components such as grommets, grommet plates, and / or other manifold blocks. As shown, the base surface 276 can include a grommet 558 ​ ​Multiple sealed pneumatic channels 574. In some examples, channel 574 can connect pressure ports 567 on surface 276F to holes 261A, 261B, 261C in the vertical plate. In other examples, channel 574 can connect pneumatic passages or holes through gasket 558 to pressure ports 567 or holes 261A, 261B, 261C. Surface 276F may include vertical plates 276A, 276B, and 276C, which can serve as mounting surfaces for corresponding adapters 270, 268, and 266, respectively. Pneumatic ports 261A, 261B, and 261C on vertical plates 276A, 276B, and 276C can be connected to corresponding adapters 270, 268, and 266 for transmitting pneumatic pressure to housing assembly 226. A secure connection between the vertical port 261 and the adapter can be established via mechanical fittings such as nut-bolt pairs, threads or push screws, or similar mechanisms. The mechanical assembly may also include blocks and intermediate components such as one or more washers 568. ​ ), the fit of washers and / or similar components.

[0150] ​

[0151] Further understanding can be gained by inspecting the pneumatic pressure source, conduits, valves, sensors, and outlet ports of manifold 260. ​ The structure and function of manifold 260. ​ In the example shown, manifold 260 has dozens of valves, sensors, and ports. The following sections describe three exemplary pathways, each including a source, valve, conduit, port, and in one example, a pressure sensor. These example pathways are for illustrative purposes. ​ and ​ The components of the manifold are combined to provide optional fluid connections between a pressure source and the actuation chambers of pneumatically driven valves and pumps, as well as fluid connections to pressure sensors. The pressure sensors provide information to the controllers of the valves to safely pump blood, dialysate, and water, thereby providing treatment to the patient.

[0152] ​ The pneumatic manifold diagram illustrates the pneumatic connection to the blood pump cartridge. (In this case, the blood pump cartridge is located on the front panel of the dialysis unit, so the blood pump cartridge is connected to the manifold using a flexible tube instead of a directional connection). ​ The pneumatic circuit selectively connects the blood actuation chamber, heparin pump, and associated valves to a high positive pressure source HP, a low positive pressure source LP, or a negative pressure source NEG. Circuit 1005 connects the blood pump BP1 to the pressure sensor P_BP1 and to the low pressure source LP via valve V_BP_POS1, and to the negative pressure source NEG via valve V_BP_NEG1.

[0153] The blood pump actuation circuit 1005 in manifold 260 is shown in ​ , ​ . The flow paths are the holes and channels of the various blocks of manifold 260. The low pressure source LP is a conduit that runs the length of T-shaped manifold block 272 in the horizontal portion 272A of the T-shaped manifold. The negative pressure source NEG is a conduit through the long axis of T-shaped manifold block 272 parallel to LP. Positive pressure flows from the LP conduit through flow channel 1012 on the top of T-shaped manifold 272, then through hole 1020 through the vertical leg 272B of the T-shaped manifold to electromechanical valve V BP POS1. When valve V BP POS1 is open, positive pressure flows up through hole 1025 in vertical leg 272B to channel 1040 on the top of T-shaped manifold 272. Low pressure then flows through hole 1060 to port 582, where a fitting allows a flexible or malleable line to connect the port to the (remote) blood pump cassette. The pressure in the blood pump connected to port 582 is monitored by a pressure sensor mounted to port P BP1. Port P BP1 is on the lower of the two upward facing surfaces of top manifold block 276. Port P BP1 is fluidically connected to channel 1040 via hole 1057 in top manifold block 276, channel 1055 on the top of middle manifold block 274, and hole 1050 through middle manifold block 274.

[0154] The circuit 1005 is shown in ​ embedded in manifold assembly 260, T-shaped manifold block 272 selectively connects the actuation chamber in the blood pump cassette (which plugs into cassette receptacle 252 in ​ ) to either the low pressure source LP or the negative pressure source NEG via two valves. The pressure sensor mounted to top manifold block 276 is fluidically connected through holes and channels in the top and middle manifold blocks. Other pneumatic circuits can connect the actuation chambers for diaphragm pumps in cassette assembly 226 to two of the low pressure source LP, the atmospheric source ATM, and the negative pressure source NEG via valves on the vertical leg 272B of T-shaped manifold block 272.

[0155] ​ The pneumatic schematic in ​The pneumatic circuit in manifold 260 selectively connects the actuation chambers of various valves (and here, just two diaphragm pumps are illustrated) on an external dialysis cartridge (ODC) to at least one of atmospheric pressure ATM, a high positive pressure source HP, a low positive pressure source LP, and a negative pressure source NEG. Circuit 1100 is an example pneumatic circuit that connects diaphragm valve V_MIX_DT in an ODC cartridge to either the ATM pressure source or the LP pressure source via three-way valve 1105. Circuit 1200 is an example pneumatic circuit that connects liquid valve V_DISINFECT in an ODC cartridge to either the HP pressure source or the NEG pressure source via three-way valve 1205.

[0156] Mix_DT valve circuit 1100 and DISINFECT valve circuit 1200 in manifold 260 are illustrated in ​ , ​ . The flow paths include the holes and channels of the various blocks of manifold 260. Pressure sources ATM, NEG, LP, HP are conduits arranged along the long axis of intermediate block 274. MIX_DT circuit 1100 connects either the low pressure source LP or the atmospheric source ATM to the outlet port V_MIX_DT for the MIX_DT liquid valve in cartridge assembly 226. The low pressure source LP is connected to valve 1105 via channel 1110 on the bottom face of intermediate manifold block 274 and hole 1115. The atmospheric source ATM is connected to valve 1105 via channel 1140 on the bottom face of intermediate manifold block 274 and hole 1145. Valve 1105 is connected to outlet port V_MIX_DT via channel 1120 on the top of intermediate manifold block 274, hole 1130 through the top manifold, and hole 1135 through adapter 268.

[0157] DISINFECT circuit 1200 connects either the high pressure source HP or the negative pressure source NEG to the outlet port V_DISINFECT for the DISINFECT liquid valve in cartridge assembly 226. The high pressure source HP is connected to valve 1205 via channel 1210 on the bottom face of intermediate manifold block 274 and hole 1215. The negative pressure source NEG is connected to valve 1205 via channel 1240 on the bottom face of intermediate manifold block 274 and hole 1245. Valve 1205 is connected to outlet port V_DISINFECT via channel 1220 on the top of intermediate manifold block 274, hole 1222 through intermediate manifold 274, channel 1224 on the bottom of intermediate manifold, hole 1226 back through intermediate manifold, channel 1228 on the top of intermediate manifold, hole 1230 through top manifold 276 and through adapter rail 268, via retainer 1235 and channel 1237.

[0158] ​It is shown how the above circuit is physically embedded within the manifold assembly 260. It is also shown how these actuation ports are mapped from the array on the riser 276B to a spatially different array of actuation ports of the manifold adapter 268, thereby providing an array of actuation ports that matches the array of actuation ports of the cartridge assembly 226.

[0159] ​ A pressure distribution manifold 260 is shown mounted in a recess 258 of the enclosure or housing 254. This arrangement can allow proper alignment between the ports 261 on the risers of the pressure distribution manifold 260 and the corresponding ports on the mating surfaces of the adapters 266, 268 and 270. In this embodiment, the manifold 260 is positioned below a certain thermal insulation 264. The insulation 264 can be provided between the body of the manifold 260 and the shelf 256. This arrangement isolates temperature sensitive electronics from the heating fluid circulating in the components inside the enclosure or housing 254.

[0160] As ​ In this embodiment of the hemodialysis apparatus 246 and the enclosure 254, the footprint of the cartridge assembly 226 extends forward from the front face of the apparatus 246, as shown in FIG. 18. With reference to a user or operator facing the hemodialysis apparatus 246, the cartridge footprint extends over the front edge of the shelf 256. To this end, one or more adapters 266, 268, 270 are configured to provide the necessary mating of the cartridge assembly 226 actuation ports 240 with their corresponding connector or receptacle ports 266P, 268P and 270P located on the interface or adapter 266, 268, 270. In this example, the adapters 266, 268, 270 function as receptacle assemblies, thereby providing a first spatial array of receptacle ports for mating with identically arranged cartridge ports 240 of each cartridge 194, 196 and 198 of the cartridge assembly 226, respectively. ​ A bottom perspective view of the enclosure 254 with the installed interfaces / adapters 266, 268, 270 is shown. In this view, the extent to which the adapters protrude out of the enclosure shelf 256 (and thus also out of the underlying pressure delivery manifold 246) is apparent.

[0161] ​ It is shown how the adapters 266, 268, 270 are mounted to the top side of the manifold risers 276A to 276C and how the adapters 266, 268, 270 protrude out of the front side of the manifold 260. The first spatial array of receptacle ports 266P, 268P and 270P is connected with the (in this case more compact) second spatial array of output ports 261 of the top blocks or risers 276A to 276C of the manifold 260. Internal channels within the adapters 266, 268, 270 are routed to the corresponding risers 276A, 276B and 276C mounted over the corresponding array of manifold output ports.​ A manifold / adapter assembly is shown with the adapters 266 removed and exploded to fully show the structure of the adapters and the risers 276C, 276A and 276B.

[0162] ​ ​ is a rear view of the manifold 260, and ​ ​ It is illustrated that the risers 276A, 276B and 276C allow the adapters 266, 268, 270 to slide from the rear of the enclosure into their respective positions in the enclosure 254 via the slots or cutouts 280, 282, 284 of the shelves 256 of the enclosure 254. The risers 276A, 276B and 276C are manufactured tall enough to allow for the placement of insulation, rigid foam insulation or other types of insulation, to provide a thermal break between the shelves 256 and the body of the manifold 260 and the electronic components (control board, sensors, etc.) located in the recess 258. (See, for example, the insulation 269A wrapped around the risers in ​ ). ​ It is shown how the assembly including the manifold 260, the attached risers of the manifold 260 and the adapters 266, 268 and 270 and other related components can be slid as a unit into position in the recess 258 of the enclosure 254.

[0163] ​ The engagement between the adapters and their respective guide rails is illustrated, with the adapters positioned within the enclosure to receive the cartridge assembly from the cartridge loading device within the housing 254. The adapter receptacles or adapter guide rails 591, 593 and 595 can be integrally incorporated with the shelves 256 of the enclosure 254 or can be separate component(s) that can be mechanically attached to the enclosure 254. In one embodiment, the shelves 256 include spaces to receive or attach the adapter guide rails 591, 593, 595. ​ A rear view (exterior view) of the enclosure 254 is specifically depicted with the adapters 266, 268, 270 partially inserted into the respective adapter guide rails 595, 593 and 591 (shown in ​ ). The manifold 260 is attached to the adapters 266, 3268, 270 prior to the manifold / adapter assembly being slid into its final position in the enclosure 254 defined by the adapters and the adapter guide rails. As shown in ​ , the guide rails 591, 593 and 595 are located in the spaces 591S, 593S and 595S, respectively. ​ A front view (interior view) is depicted with the adapters 266, 268 and 270 partially received into their respective adapter guide rails in the enclosure 254.​​

[0164] Proper alignment of the adapters 266, 268, 270 and the pneumatic manifold 260 can be important to ensure that the plurality of pneumatic ports 240 of the cassette assembly 226 are aligned with the mating receiver ports 266P, 268P, 270P to provide the necessary pneumatic connections with the cassette assembly 226. The final position of the adapters is defined by the adapter rails that are mounted in a form fit manner on the same enclosure that mounts the cassette loader 292 on the top of the enclosure 254. Accordingly, the retention mechanisms for the above components should be properly positioned to achieve alignment of the pneumatic ports between the three components, namely the cassette assembly 226, the adapters 266, 268, 270 and the pneumatic manifold 260. ​ A cassette loader 292 with an operating handle 308 is depicted. The cassette loader 292 can be mounted on the inner surface of the top 604 of the housing or enclosure 254. As illustrated, the cassette loader 292 and the adapter rails 591, 593 and 595 are positioned on opposite surfaces of the enclosure 254 and maintain a fixed spatial relationship with each other.

[0165] ​ An example adapter rail 591 is depicted that can include a headrest portion or flange 592 and a tray portion 597 with a raised platform 596 that can partially or completely occupy the tray portion 587. The headrest portion 592 forms a frame of the rail 591 with the tray portion 597. The tray portion 597 can receive a corresponding adapter and the corresponding adapter can rest on the raised platform 596. The tray portion 597 can also include a fence profile 594 that can bend according to the edges of the corresponding adapter received in the rail 591 so that the adapter can slide down into the receiving rail. In this embodiment, the tray portion 597 can also provide a cutout area 597 where the received adapter can interface with a corresponding jamb on the pneumatic manifold 260. An elongated slot or groove 611 can optionally be provided between the sides of the raised platform 596 and the fence profile 594. The elongated groove 611 can collect any leaked liquid and help divert any leaked liquid or condensation away from the top surface of the mounted adapter that can risk reaching the electronics provided below the shelves 256 or in the recessed area 258.

[0166] ​ and ​ An exploded view of an example adapter 266 and its interaction with a corresponding jamb 276C is depicted. More specifically, ​ A top view of a plurality of plates and one or more gaskets that can collectively form the adapter 266 is depicted. And ​A bottom view of the same exploded view depicts the adapter 266. The adapter is arranged to provide independent pneumatic pathways between the first port array of the housing assembly 226 and the second port array of the pneumatic manifold 260. In this example, the pneumatic ports 240 on the housing assembly are distributed over a narrow-dimension extended surface region remote from the manifold assembly 260. The adapter is used to converge the first larger spatial array into a smaller spatial array of pneumatic ports 261 on the vertical plate of the manifold 260. ​ and ​ As shown, the exemplary adapter 266 may include multiple layers or plates with pneumatic openings and channels that converge into smaller surface areas as the layers advance toward their respective vertical plates. The top plate 280 of the adapter 266 includes a pneumatic port 271 and connection features for engaging with a plate at the rear of the adapter. This can be achieved through... ​ Top view of the top plate 280 and as shown ​ The bottom view of the top plate 280 shown reveals pneumatic ports 271 and connection features 293. The top plate 280 rests on an intermediate block 286, which includes corresponding pneumatic ports 285 located on its first surface 286A. These pneumatic ports 285 coincide with the pneumatic ports 271 on the top plate 280. A scraping washer 282 can be received in a washer receiving portion 281 recessed into the first surface of the intermediate block 286. The continuous elastomeric washer 282 can be molded to form a properly positioned scraping seal 284. The scraping seal 284 provides a sufficient sealing engagement between the cartridge port 240 and the corresponding adapter receiving port 271, while providing lower frictional resistance for the installation and removal of the cartridge assembly 226 compared to, for example, a separate O-ring seal.

[0167] ​An opposite, second surface 286B of the intermediate block 286 is depicted. This surface includes pneumatic channels 286C that are in fluid communication with the ports 281 on the first surface 286A. The channels 285C can be arranged to converge the pneumatic ports 281 on the first surface 286A and connect to a distribution of pneumatic ports on the second surface 286B. As depicted, the pneumatic ports on the second surface 286B occupy a smaller area and a different spatial array than the pneumatic ports on the first surface 286A. The channels 285C ensure that the pneumatic ports 281 converge or shift toward the port array on the stave side of the adapter 266. The second intermediate block 290 can include pneumatic ports 288 to coincide with the array of pneumatic ports disposed on the second surface 286B of the intermediate block 286. A second gasket 289 can be positioned between the first intermediate block 285 and the second intermediate block 290. The gasket 289 can allow for proper sealing between the first intermediate block 286 and the second intermediate block 290 and allow for compression of the gasket to the degree necessary to create a seal. In one embodiment, a set of alignment features can be disposed on one or both of the gasket 289 and the abutting plates. In this case, the plates can be the first intermediate block 286 and the second intermediate block 290. Further, the transition gasket 289 can include pneumatic ports that correspond to the pneumatic ports 285 on the first intermediate block 286 and the pneumatic ports 288 on the second intermediate block 290. A stave gasket 291 can be positioned between the second intermediate block 290 and the corresponding stave, in this example, stave 276C. This gasket is arranged to seal the interaction between the second intermediate block 290 and the stave 276C. A plurality of gasket alignment features can be disposed on the mating surfaces of the second intermediate block 286 and the stave 276C. The foregoing discussion is equally intended to apply to the adapters 268, 270 and the interacting staves 276B and 276A. The number and spatial distribution of pneumatic ports can differ on other adapter-stave interaction embodiments and do differ in this embodiment.

[0168] When there is pneumatic interaction between ports, the sealing components between the ports typically include O-rings. In the case of an adapter, multiple O-rings can be used to ensure a sealed engagement between the mating ports. However, multiple spatially arrayed O-rings can exhibit relatively poor alignment tolerances when inserting the multiple pneumatic ports 240 into the corresponding adapter ports. In addition to the tolerance issues, multiple O-ring connections can create a greater engagement / disengagement engagement force between the cartridge assembly 226 and the associated adapter of the cartridge assembly 226 than desired. In an alternative arrangement, a web of a wiper gasket can be employed to create the desired seal and can be mounted between two interacting plates or blocks of an adapter. ​An exemplary wiper gasket 284 is illustrated, which can be molded as a single unit, greatly simplifying the assembly and installation procedure. ​ An exemplary wiper gasket for one of the manifold adapters is depicted. ​ A cross-sectional view of the wiper gasket of ​ is shown taken along line 33H-33H. As illustrated, the gasket 284 can be formed to encircle the port 285 in an annular fashion and form a tapered peripheral recess toward the pneumatic port 285. The gasket 284 can optionally include an annular nub or ridge 283 built into the wiper gasket 284 to cover a portion of the port 285. This arrangement and structure of the wiper gasket 284 can allow the cartridge port 240 to be inserted with an acceptable amount of force and can also ensure a seal between the adapter and cartridge during operation, i.e., during the application of positive and negative pressure through the ports of the adapter.

[0169] ​ and ​ A cartridge seating device or cartridge loader 292 is shown for securing a first side of a cartridge assembly 226 for linear movement of the cartridge assembly toward or away from one or more array of receiving assemblies arranged to mate with corresponding arrays of cartridge ports 240 on one or more of the cartridges 228, 230 and 232 on an opposite second side of the cartridge assembly 226. In the example described below, the receiving assemblies include manifold adapters 266, 268, 270, but the cartridge loader can be used in any other system in which a ported cartridge is to be plugged into and unplugged from any type of receiving array, including, for example, fixed multi-port receiving or movable connectors equipped with an array of ports, among other possibilities. Rather than being arranged on the exemplary adapters 266, 268, 270 shown, the receiving ports connected with the cartridge actuation ports can also be arranged on a frame, housing or even directly on the manifold output port array, as long as the two sets of mating ports can be arranged to properly align. The cartridge seating device 292 has the general utility of assisting a ported cartridge to engage or disengage with mating connectors or receiving ports on any device.

[0170] ​ The cartridge loader 292 is shown in a retracted position, linearly moving the cartridge assembly away from ​ the receiving ports 261b of ​ , ​ , ​ the ports 266P, 268P and 270P of ​more generic ports 271 arranged on the adapters 266, 268, 270 in this example. It should be noted that a cartridge seating device or cartridge loader 292 can be used to seat or unseat a cartridge or cartridge assembly onto or from the receiver assembly, so long as the individual cartridge or cartridge assembly has a liquid port or actuation port on the side opposite the side that is secured by the cartridge seating device 292.

[0171] In this example, the cartridge seating device 292 includes a fixed frame 294 that includes fixed members 296a, 296b. The fixed members 296a, 296b are coupled to a linkage that in turn interacts with a movable cartridge mount 298. The movable cartridge mount 298 is configured to hold a cartridge or cartridge assembly, and in this example the movable cartridge mount 298 includes flanges 300a, 300b that lead to cartridge mount rails 302a, 302b. In this example, the cartridge mount rails 300a, 302b allow a cartridge or cartridge assembly to be slid into place and held on the seating device 292. Other examples can include a clamping device that can grip a cartridge or cartridge assembly. In this example, independent motion of a mounted cartridge or cartridge assembly is limited by the presence of one or more lateral members 304 that limit top side motion of a mounted cartridge or cartridge assembly and by actuator arms 306a, 306b of an operating handle 308 that move into position to interfere with lateral motion of a mounted cartridge or cartridge assembly.

[0172] As ​As shown in the middle, the linkage can include two or more swing arms 310a, 310b each pivotally connected at a first end 312 to a fixed member 296a, 296b. Each of the swing arms 310a, 310b is arranged to move in a plane that is generally parallel to the direction of motion of the cartridge mount 298 relative to the fixed member 296a, 296b. The second end of each swing arm 308a, 308b includes a hub 316 coupled to a shaft or shaft gear 318 configured to interact with a flange 300a or 300b that is generally parallel to the plane of motion of the swing arms 310a, 310b. The shaft or shaft gear 318 is positioned within an elongated slot 320 in the flange 300a or 300b that translates the arcuate motion of the second end of the swing arms 310a, 310b toward or away from the fixed member 296a, 296b into linear motion of the cartridge mount rail 302a, 302b toward or away from the fixed member 296a, 296b. In this example, the shaft or shaft gear 318 optionally extends from the flange 300a to the flange 300b to also serve as the cross member 304. The shaft or shaft gear 318 can slideably interact with the slot 320, or can interact with the slot 320 in other ways, such as for example by a circular bearing or wheel positioned in the slot 320.

[0173] To help ensure linear motion of the cartridge mount 298, one or more guide elements, such as for example posts 322, can optionally be included to limit lateral motion of the cartridge mount 298 and its attached mount rail 302a, 302b. The guide elements 322 can be rigidly attached or mounted to the fixed frame 294 (or alternatively to the fixed member 296a, 296b) and extend along the desired direction of motion of the cartridge mount rail 302a, 302b. The guide elements 322 can interact with the cartridge mount 298 (or alternatively with the flange 300a or 300b, or with the mount rail 302a or 302b) through guide holes 324 (or guide rails, tracks or other elements) that limit the relative motion of the cartridge mount 298 in the fore-aft direction relative to the frame 294 or fixed member 296a, 296b.

[0174] ​ The cartridge seating device 292 is shown in a nearly fully retracted position, with the cartridge mount 298 retracted away from the associated receiving assembly enough to disengage the cartridge actuation port (or cartridge liquid port) of an installed cartridge from its respective receiving port. (See for example ​ 、 ​ ). ​The cartridge seating device 292 is shown in the engaged position, wherein the cartridge mount is linearly extended away from the fixed frame 294 or fixed members 296a, 296b sufficient to engage the cartridge actuation port (or cartridge fluid port) of the mounted cartridge with its corresponding receiving port. The actuator arms 306a, 306b of the handle 308 are pivotally connected to the fixed members 296a, 296b on the distal end 326. In addition, each actuator arm 306a, 306b is pivotally connected to a first end of a connecting member 330a, 330b on a more proximal portion 328 of the arm 306a, 306b. The second end of the connecting member 330a, 330b is then pivotally connected to an actuator rod 332 having a pivotal connection to the second end of each swing arm 310a, 310b of the linkage mechanism comprising the cartridge seating device 292. The rotation axis of the connecting member 330a or 330b relative to the actuator arm 306a or 306b is eccentrically moved, which allows the actuator rod 332a, 332b and swing arms 310a, 310b to be displaced away from the fixed members 296a, 296b.

[0175] Optionally, a cartridge mount retention member 334 can be used to retain the cartridge mount 298 in the retracted position. In one example, the cartridge mount retention member 298 can comprise a pawl that is pushed out of the way by the cross member 304 (or alternatively, by another element attached to the cartridge mount 298, flange 300, rail 302, or shaft / axle gear 318) when the handle 308 is fully pulled into the retracted position (see ​ ). When the cross member 304 reaches the pawl recess 336, the pawl recess 336 drops to engage the cross member 304 and retain the cartridge mount 298 in its retracted position. In additional or alternative embodiments, the handle 308 can comprise a movable plunger element (instead of the handle post 338, see ​ , ​ ) that can engage or penetrate a hole or recess (not shown) in a front flange 340 of the fixed frame 294. Optionally, the plunger can be spring loaded to automatically engage the front flange when the handle 308 is released by the user.

[0176] The cartridge seating device 292 when applied to the hemodialysis enclosure 254 (see ​ ) can be mounted to the top plate of the interior of the enclosure 254 as shown in ​ and ​ . The cartridge seating device 292 is in an opposing position to the receiving port assemblies 266, 268, 270 (in this case, a manifold adapter). It can be observed that the cartridge assembly 226 is mounted in the cartridge seating device 292 by means of, for example, a cartridge assembly frame plate 513 as shown in Figure 21 and Figure 46 . In this example, the cartridge assembly 226 is mounted in the cartridge seating device 292 by means of a cartridge assembly frame plate 513 as shown inFigure 30 and Figure 31 In this case, the cartridge assembly ports 240 are shown directly adjacent to the corresponding receptacle ports on the receptacle assembly, and the cartridge assembly ports 240 are fully disengaged from the corresponding receptacle ports on the receptacle assembly when the handle 308 is seated in the retracted position Figure 30 ).

[0177] Pneumatic pump system using binary valve

[0178] Figure 60 is a schematic diagram showing an embodiment of a pressure actuation system 14000 for a positive displacement diaphragm pump ("pod pump") 234, such as the pump shown in Figure 20 In this example, air pressure is used as the control fluid (e.g., so that the pump is pneumatically driven). In other embodiments, other fluids (e.g., water or a water-based solution) can be used as the control fluid.

[0179] In Figure 60 , the pressure actuation system 14000 alternately provides positive and negative gas pressure in the actuation chamber 14020 of the pod pump 23a. The pneumatic actuation system 14000 includes an actuation chamber pressure transducer 14020, a positive supply valve LP1, a negative supply valve N1, a positive pressure gas source LPOS, a negative pressure gas source NEG, a positive pressure source pressure transducer (not shown), a negative pressure source pressure transducer (not shown), and an electronic controller 14035. The electronic controller receives pressure data from the pressure sensor 14020 and controls the valves N1, LP1 to control the operation of the pump 23a. These two valves are controlled by the electronic controller 14035. (Alternatively, a single three-way valve can be used in place of the two separate valves LP1, N1.) In some cases, the positive supply valve LP1 and the negative supply valve N1 are binary on / off valves.

[0180] The positive pressure source LPOS provides positive pressurized control gas to the actuation chamber 14020 to urge the diaphragm 14025 in a direction that minimizes the volume of the pumping chamber 14027 (i.e., the position of the diaphragm against the rigid pumping chamber wall). The negative pressure source NEG provides negative pressurized control gas to the actuation chamber 14020 to urge the diaphragm 14025 in the opposite direction that maximizes the volume of the pumping chamber 14027 (i.e., the position of the diaphragm against the rigid actuation chamber wall).

[0181] The controller 14035 can also receive pressure information from three other pressure transducers: the actuation chamber pressure transducer 14020, a transducer on the LPOS, and a transducer on the NEG. As the names suggest, these transducers measure the pressure in the actuation chamber 14020, the positive pressure source LPOS, and the negative pressure source NEG, respectively. The controller 14035 monitors the pressure in both sources LPOS, NEG to ensure that both sources LPOS, NEG are properly pressurized (in a positive or negative manner). One or more compressor-type pumps can be used to maintain the desired pressure in the reservoirs including the sources for LPOS, NEG.

[0182] In one embodiment, the pressure provided by the positive pressure reservoir LPOS is of sufficient magnitude under normal conditions to push the diaphragm 14025 all the way against the rigid pumping chamber wall. Similarly, the negative pressure (i.e., vacuum) provided by the negative pressure source NEG is preferably of sufficient magnitude under normal conditions to pull the diaphragm all the way against the rigid actuation chamber wall. However, in a preferred embodiment, the positive and negative pressures provided by the sources LPOS, NEG are maintained within sufficiently safe limits to avoid excessive liquid pressures that could harm a patient to which the pumping system can be connected.

[0183] The controller 14035 monitors the pressure information from the actuation chamber pressure transducer 196 and, based on that information and possibly based on a timer, controls the valve mechanism (valves LP1, N1) to push the diaphragm 14025 all the way to its minimum pumping chamber volume position and then switch the pressures to pull the diaphragm 14025 all the way back to its maximum pumping chamber volume position.

[0184] The pressure actuation system includes a pressure distribution manifold, which can include the actuation chamber pressure transducer 14020, a transducer for the LPOS source, a transducer for the NEG source, the positive supply valve LP1, the negative supply valve N1. The controller 14035 can be mounted on the manifold, and the positive pressure gas source LPOS and the negative pressure gas source NEG can include conduits that extend through the manifold. The manifold can be configured to fit entirely or mostly in the hemodialysis housing recess 258 (see, e.g., Figure 44 、 Figure 48 ). In this arrangement, the components in contact with blood or dialysate (i.e., the pod pump 23a, the inlet valve 192, and the outlet valve 193) can be located in the isolated enclosure 254 or the front panel 248 (see Figure 23 ), so that the pump, valves, and interconnecting liquid paths can be more easily accessed and / or sterilized.

[0185] Pumping process with binary valve

[0186] Referring to Figure 61 and Figure 62This allows for a better understanding of the process of pumping liquid via podded pump 23a. Now refer to... Figure 61 For a conveying stroke and a filling stroke, the target pressure of 14050 and the pressure sensor 196 were plotted relative to time. Figure 60 The measured actual pressure is 14055. The delivery stroke includes using positive pressure from the LPOS source to drive the diaphragm 14025 from one side of the pump pod 23a to the other and to discharge liquid from the pump chamber 14027. Conversely, the fill stroke uses sub-atmospheric pressure from the NEG source to pull the diaphragm 14025 back through the pod pump 23a and to fill the pod pump with liquid. In some examples, the fill stroke is completed by connecting the actuation chamber 14020 to the atmosphere, allowing the liquid pressure in the system to drive the diaphragm through the pod pump chamber.

[0187] In the binary valve-driven pump 14000, the delivery pump stroke and the filling pump stroke include multiple filling cycles, which generate... Figure 61 and Figure 62 The serrated pressure trace at 14050. Details of the start of the delivery stroke are in... Figure 62 As shown, during liquid movement, the actual pressure 14055 increases when valve LP1 opens and decreases when valve LP1 closes. During the delivery stroke, liquid movement from pumping chamber 14027 reduces the volume of the pumping chamber; and since the total volume of the podded pump is fixed, this increases the volume of actuation chamber 14020. If pneumatic valve LP1 closes, the increased volume of the actuation chamber causes a decrease in pressure within the actuation chamber. The charging cycle includes a pressure rise due to the open valve and a pressure decay when the valve closes. The length of the charging cycle may vary, such as... Figure 62 As shown in the figure, three complete charge cycles are illustrated, and each charge cycle has a different duration. Figure 62 The details of the conveying stroke, in which a positive pressure is applied, are drawn. Now refer to... Figure 61 During the filling stroke, the pressure trace 14055 exhibits a similar serrated pattern. However, during the filling stroke, the pressure drops rapidly as the N1 valve opens, exposing the actuation chamber to the NEG source, while the pressure recovers more slowly toward atmospheric pressure as the N1 valve closes. Furthermore, the charging cycle includes a rapid increase in the magnitude of the actuation chamber pressure and a slower pressure decay toward atmospheric pressure as the N1 valve closes.

[0188] In previous applications and disclosures, diaphragm pumps were controlled using continuously variable valves, in this document binary valves are described as being either fully open or fully closed and are not designed to be partially open. Binary valves and associated control electronics are typically less expensive than variable open valves. Additionally, binary valves can require less functional checking / monitoring and binary valves can be less sensitive to the presence of debris in the pneumatic pathways leading to or away from the binary valve. The inherent digital or on / off functionality of binary valves requires unique control algorithms for pressure control as well as end of stroke and flow path occlusion detection.

[0189] Controller 14035 controls valves N1 and LP1 based on signals received from pressure sensors or transducers 196 according to a variety of algorithms that can run sequentially or simultaneously. These control algorithms are unique to binary valves due to the inherent digital or on / off functionality of binary valves. Control algorithms include algorithms to control fluid flow rate through the pump, algorithms to control pressure inside the actuation chamber 14020, algorithms to detect end of stroke (EOS) conditions, algorithms to detect complete occlusion of the inlet line, algorithms to detect complete occlusion of the outlet line, algorithms to detect partial occlusion, and algorithms to measure access metrics (an indication of the quality of blood flow obtained from the patient's vein or fistula access).

[0190] Controller 14035 calculates information about liquid flow through the pump based on pressure signals from sensors 196 when valves N1, LP1 are closed. Controller 14035 uses the received pressure data to control actuation chamber pressure, detect EOS, occlusion, partial occlusion, and determine access metrics.

[0191] Pressure control description

[0192] Flow rate through a pneumatic actuated diaphragm pump, such as pod pump 23a, is controlled by setting a target pressure for the actuation chamber 14020. Pod controller 14035 then controls the pressure in actuation chamber 14020 by controlling valves N1, LP1, which fluidly connect a pressure source to the actuation chamber of the pump, by controlling valves N1, LP1. In an example control algorithm, the controller averages the pressure data from pressure sensor 196 when binary valves N1, LP1 are closed, and the controller opens valves N1, LP1 when the accumulated average pressure approaches or equals the target pressure. In one example, controller 14035 closes valves N1, LP1 when the magnitude of the pressure data equals or exceeds the target pressure. In one example, controller 14035 closes valves N1, LP1 when the magnitude of the pressure data equals or exceeds the target pressure minus a predetermined constant value. In another example, the predetermined value is not constant, but varies with the direction of the stroke and the duration or phase of the stroke. In another example, controller 14035 integrates the difference between the magnitude of the measured pressure and the magnitude of the target pressure, and controller 14035 opens valves N1, LP1 when the integrated difference approaches or equals zero.

[0193] Fluid flow through the pump is controlled by the magnitude of the negative pressure applied to the actuation chamber to fill the pumping chamber with liquid and the magnitude of the positive pressure applied to the actuation chamber to deliver liquid from the pumping chamber. In some examples, pod pump controller 14035 is programmed to receive or calculate a desired flow rate and / or maximum displacement volume for pod pump 23a. Controller 14035 can set an initial target pressure for the fill stroke and the delivery stroke. The controller controls the pressure in the actuation chamber to reach or approach the target pressure. The controller monitors the time to complete the stroke, and determines the actual flow rate by dividing the displacement volume by the stroke completion time. Controller 14035 can change the target pressure based on the difference between the most recent actual flow rate and the desired flow rate. For example, if the measured actual flow rate is lower than the desired flow rate, controller 14035 can increase the target pressure. In another example, if the measured actual flow rate is higher than the desired flow rate, the controller can decrease the target pressure. Controller 14035 can modify the delivery stroke independently of the fill stroke. In one example, controller 14035 can use a feedback loop that modifies the delivery target pressure based on the measured flow rate during the delivery stroke to obtain the desired flow rate. In another example, the feedback loop modifies the negative fill target pressure based on the measured flow rate during the fill stroke to obtain the desired fill rate.

[0194] In previous disclosures, chambers connected to a pressure source through a binary valve have been controlled based on a limit on the target pressure. When the magnitude of the pressure measured in the chamber is below a certain predetermined amount of the target pressure magnitude, the controller will connect the pressure source to the chamber by opening the valve between the pressure source and the chamber. Then, when the magnitude of the pressure measured in the chamber is above a second predetermined value of the target pressure magnitude, the controller will close the valve. In some cases, applying this limit method to a pneumatic diaphragm pump results in an average chamber pressure magnitude that is less than the target pressure magnitude. In some cases, opening the valve results in a very rapid increase in the magnitude of the pressure in the chamber, while the decrease in the magnitude of the pressure due to liquid flowing into or out of the pumping chamber is much slower. This mismatch in the rate of change of pressure causes the magnitude of the time-averaged pressure to deviate below the target pressure magnitude. In cases where the flow of liquid into or out of the pump varies over time, the deviation between the average pressure and the target pressure also varies over time, making it difficult to continuously correct for the mismatch in the rate of change of pressure.

[0195] The pressure in the actuation chamber can be controlled by comparing the measured pressure to the target pressure. The controller opens and closes pneumatic valves that connect the actuation chamber to a pressure source or reservoir. The controller can open and close valve LP1 during a delivery stroke to maintain the pressure in actuation chamber 14030 near the delivery target pressure 14052. Controller 14035 opens and closes valve N1 during a fill stroke to maintain the pressure in actuation chamber 14030 near the fill target pressure 14054. In one example, the controller closes the pneumatic valve when the magnitude of the measured pressure exceeds the target pressure, and reopens the pneumatic valve when the average measured pressure in the actuation chamber approaches or equals the target pressure.

[0196] In Figure 63 and Figure 64 , the controller 14035 controls valves N1, LP1 to maintain the average pressure in actuation chamber 14020 at the target pressure in a manner that maintains the average pressure in the actuation chamber at the target pressure when valves N1, LP1 are closed, with reference to Figure 62 and the description that follows. Referring now to the pressure control algorithm 14100 in Figure 63 and with reference to Figure 60 , the pump controller, which can be the same as Figure 60The controller 14035 in the fill process 14000 selects the stroke direction 14105 and the target pressure, i.e., fill and PTF (fill target pressure) or delivery and PTD (delivery target pressure). If a fill stroke is selected, then in 14110 the controller 14035 opens the valve that fluidly connects the NEG source or reservoir to the actuation chamber 14020, and in 14120 the controller 14035 monitors the pressure sensor 196. In block 14130, the controller evaluates at each time step whether the pressure magnitude is greater than the target pressure magnitude, and if the pressure magnitude is not greater than the target pressure magnitude, the valve is left open. In block 14140, once the measured pressure magnitude is equal to or greater than the target pressure, the Nl valve is closed. In block 14150, the difference between the measured pressure P and the target pressure TTF is summed at each time step. In block 14160, the stroke end function or algorithm checks for stroke end, and if the EOS criteria are met, the controller logic is directed to stroke end 14200. It should be noted that the logic in block 14160 can be positioned anywhere in the flowchart between 14140 and 14180, or the logic in block 14160 can be a function separate from the pressure control algorithm 14100. In block 14170, the summed pressure difference is compared to zero. If the summed pressure difference is greater than zero, the controller logic returns to 14150 for additional time steps. In the event that the sum of the pressure difference is equal to or less than zero, the controller logic zeros the pressure difference sum in block 14180, and the controller logic returns logic to block 14110 where the Nl valve is opened.

[0197] A single controller can coordinate the timing of the pump stroke, the setting of the target pressure, and the operation of the pneumatic control valve. Alternatively, the tasks can be divided between two or more controllers, e.g., where a master controller determines the timing of the pump stroke and the target pressure, and a slave controller controls the pneumatic control valve. Reference is made to Figure 63 and Figure 60 If the master controller selects a delivery stroke, the master controller also defines the target pressure, and the slave controller moves logic to block 14210 Figure 63 ), where the LPl valve is opened. In a series of steps similar to the fill process, the pressure in the actuation chamber 14020 is monitored by the pressure sensor 196 in block 14220. Block 14230 evaluates the pressure relative to the target pressure, and if the measured pressure is equal to or greater than the target pressure, the logic is directed to block 14240, where the LPl valve is closed. Reference is now made to Figure 60In the case where the chamber pressure exceeds the target pressure, the chamber pressure 14055 continues to increase after the LP1 valve is commanded to close at 14051. Due to the delay in valve closing and due to the fluid / thermal dynamics that can affect the chamber pressure, the chamber pressure 14055 can increase to 14052.

[0198] Referring to Figure 63 In block 14250, the difference between the chamber pressure P and the target pressure PTD is summed for each time step. The sum of the difference between the chamber pressure P and the target pressure PTD from point 14052 until the chamber pressure 14055 equals the target pressure 14050 is Figure 62 Region 14080 in the sum of the difference between the chamber pressure and the target pressure when the magnitude of the chamber pressure 14055 is less than the magnitude of the target pressure 14050. Referring again to Figure 63 In block 14260, the EOS algorithm is run and if EOS is detected, the stroke ends at 14200.

[0199] In block 14270, the sum of the pressure difference from block 14250 is evaluated. If the sum of the pressure difference is less than or equal to zero, block 14270 directs the logic to 14210 where the LP1 valve is reopened. Prior to the logic reaching block 14210 to open the LP1, the pressure difference sum is set to zero in block 14280. Alternatively, the pressure difference sum can be zeroed at any time in the logic after block 14270 and prior to block 14240.

[0200] Referring now to Figure 62 The criteria of block 14270 can be represented in graphical form as the following example where the area of 14080 is equal to the area of 14085. The criteria of block 14270 is satisfied when the sum of the actual pressure 14055 minus the target pressure 14050 (for actual pressure greater than target pressure) is equal to the sum of the target pressure 14050 minus the chamber pressure 14055 (for chamber pressure less than target pressure). Alternatively, the criteria of 14270 is satisfied when the sum of [average pressure magnitude minus target pressure magnitude] is equal to or less than zero.

[0201] In one example, in blocks 14130 & 14230, the chamber pressure P is compared to a predetermined pressure PD, PF that is different from the target pressure PTD, PTF due to a pressure offset. In some examples, to limit overshoot of the pressure, the magnitude of PD, PF is a predetermined value less than the magnitude of the target pressure PTD, PTF. Referring now to Figure 62 If PD is less than the target pressure (14050D), then Figure 60The signal to the valve LP1 in 14052 will be faster and the peak pressure at 14052 will be lower. In one example, the magnitude of the pressure deviation is different for the fill stroke and the delivery stroke because the average pressure for the fill stroke and the delivery stroke is different.

[0202] Because the delay in valve actuation is a fixed value and the pressure overshoot is inversely proportional to the volume of the actuation chamber (which changes during the stroke), the overshoot can also vary, as can be observed in Figure 61 . Generally, the overshoot is largest at the beginning of the delivery stroke 14060 and at the end of the fill stroke 14075 when the actuation chamber 14020 volume has the smallest volume. The deviation for the fill stroke and the delivery stroke can vary during the stroke. In one example, the deviation magnitude is largest at the beginning of the delivery stroke and decreases with each charging cycle until the deviation reaches a minimum value. In the same or another example, the deviation magnitude is smallest at the beginning of the fill stroke and increases with each charging cycle until the deviation reaches a maximum value. The deviation value can vary with time, number of charging cycles, number of valve openings, or total pressure difference when the valve is closed during the stroke.

[0203] Another example of a pressure control algorithm 14300 is shown in Figure 64 . In addition to elements 14350, 14370, 14380, 14450, 14470, and 14480, algorithm 14300 is similar to algorithm 14100 in which the average pressure replaces the difference between the measured pressure and the target pressure. In blocks 14350 and 14450, the measurements of the pressure sensor 196 are averaged when the valves N1, LP1 are closed. In blocks 14370 and 14470, the logic proceeds to blocks 1410, 14210 to open the valves N1, LP1, respectively, after zeroing the average pressure if the average pressure PAVG is equal to the target pressure within some predetermined margin.

[0204] Detection of end of stroke

[0205] The accurate or reliable determination of the flow rate and the flow volume of the pump 23a, as shown in Figure 60 , depends on an accurate or reliable algorithm to determine the end of stroke (EOS). The end of stroke occurs when the diaphragm 14025 has moved past the cavity of the pump body and reached one of the walls of the pump body. The controller 14035 detects the condition of the chamber against the wall by observing that the chamber pressure magnitude measured by the pressure sensor 196 does not decrease when the valves N1, LP1 are closed. The chamber pressure does not decrease because the diaphragm 14025 is against the wall of the chamber and cannot move, and thus cannot change the volume of the actuation chamber 14020.

[0206] The EOS detection algorithm detects the end of stroke condition based on the valve state, the chamber pressure and the rate of change of the chamber pressure. The algorithm detects the EOS condition for a pneumatically driven diaphragm pump, where the pneumatic pressure is controlled by a pneumatic valve connecting the pump to a pressure reservoir, a pressure sensor measuring the pneumatic pressure applied to the pump and a controller in communication with the pump and the pneumatic valve. In one example, the EOS detection is based on the number of prime cycles performed by the pneumatic valve and the rate of change of the pressure when the pneumatic valve is closed. In another example, EOS is indicated when a predetermined number of prime cycles have occurred and the rate of change of the pressure magnitude is less than a predetermined rate. In another example, EOS detection is indicated when a predetermined number of prime cycles have occurred, the pressure is within a predetermined range and the rate of change of the pressure magnitude is less than a predetermined rate.

[0207] Reference will now be made to Figure 60 , the controller 14035 changes the direction of the stroke from delivery to fill or from fill to delivery after detecting the end of stroke (EOS). The end of stroke algorithm is described schematically in Figure 65 and can be understood with reference to Figure 61 . The EOS algorithm 14300 runs as part of the pressure control algorithm 14100 in blocks 14160 and 14260 or the EOS algorithm can run in a parallel fashion. Block 14310 monitors the pressure in the actuation chamber sensed by the pressure sensor 196 Figure 60 ). In block 14320, the number of prime cycles that have occurred during the current stroke is compared to a predetermined number. If more than the predetermined number of prime cycles have occurred, then the minimum rate of change of the pressure magnitude (dP / dt) is compared to a predetermined rate (dPEOS) in block 14330. If the minimum rate is less than the predetermined rate, then the difference between the current pressure P and the target pressure PT is evaluated in block 14340. If the difference is less than a predetermined difference DP, then EOS is indicated and the controller changes the pump stroke, the target pressure and switches the state of the hydraulic valves 192, 193 (the valves in the presently described dialysis system can be diaphragm valves that can also be actuated by pressure delivered through a manifold and controlled by the controller). If the difference between the chamber pressure and the target pressure is greater than the predetermined difference, then the controller 14035 indicates a blockage.

[0208] Still referring to Figure 65 , in block 14330, dP / dt is the minimum rate of change of the pressure magnitude in the actuation chamber. In some examples, the minimum rate is determined only when the pneumatic valve N1, LP1 is closed. In some examples, the minimum rate of change of the pressure magnitude is derived from a low pass filtering of the pressure values. In another example, the rate of change of the pressure magnitude is itself low pass filtered before being compared to the predetermined rate of pressure change (dPEOS).

[0209] Obstruction detection

[0210] Referring now to Figure 60 , the controller 14035 can be configured to detect occlusions in flow to and from the pump 23a. The user interface can signal a warning or alarm that the inlet or outlet line is occluded. In one example, the user can be instructed to check the blood lines 203 and 204 for kinks, compression, or other occluding factors. The occlusion detection algorithm can be considered a safety feature to prevent thrombus formation in the blood circuit, or the occlusion detection algorithm can identify problems related to fluid flow in the water or dialysate circuit.

[0211] Occlusions in the pump inlet and outlet lines are detected by the controller 14035 based on information received from the pressure sensor 196 while the actuation chamber 14020 is isolated from the pressure reservoir NEG, LPOS. The pressure sensor 196 measures the pressure in the actuation chamber. The controller 14035 detects occlusions in the inlet line during fill strokes and in the outlet line during delivery strokes. The controller 14035 sums the pressure changes that occur in the actuation chamber while the valves N1, LP1 are closed. The controller 14035 determines whether an occlusion is present by comparing the sum of the pressure changes in all the fill cycles during a single pump stroke to the sum of the pressure differences during previous strokes and to a predetermined value. The controller 14035 can also base the detection of an occlusion on the number of fill cycles completed before the end of the stroke is detected and / or the difference between the actuation chamber pressure and the target pressure.

[0212] Referring now to Figure 66 , in Figure 66 , the occlusion algorithm 14400 is represented as a flow chart that begins with step 14410 in which a fill stroke or delivery stroke is initiated by setting a target pressure, and then the flow chart opens the valves N1, LP1 Figure 60 ) in step 14415. The valves N1, LP1 are closed in step 14420. In step 14425, the controller sums the pressure changes (dPSUM) while the pneumatic valves N1, LP1 are closed. The sum of the pressure changes (dPSUM) is summed over the entire stroke, including multiple fill cycles 14427. In one example, the controller 14035 determines the pressure change Pi-1-Pi from the previous time step to the current time step and adds that pressure change to the current sum of pressure changes for each time step in which the pneumatic valves N1, LP1 are closed. In one example, the controller determines the pressure change between the time the valve N1, LP1 is closed and the time it is then reopened, and then adds that pressure change to the sum of the pressure changes (dPSUM) that includes all the pressure changes since the stroke began at step 14410.

[0213] With continued reference to Figure 66 , the occlusion algorithm 14400 checks for an end of stroke condition in step 14430 after updating the sum of pressure changes (dPSUM) in step 14425. If an EOS is not detected, the controller 14035 checks to see if the charge cycle is complete and if it is time to reopen the valve in step 14435. The end of charge cycle step 14435 can be completed based on one or more parameters including, but not limited to, the current pressure, the average pressure during the current charge cycle, or the integral of the pressure difference between the target pressure during the current charge cycle and the chamber pressure. If step 14435 determines that the charge cycle is not complete, the sum of pressure changes is updated in step 14435 for the next time step. If the charge cycle is complete, the pneumatic valve N1, LP1 is reopened in step 14415.

[0214] When an end of stroke is determined in step 14430, the occlusion algorithm 14400 performs multiple independent occlusion tests in steps 14440, 14450, 14455, 14460. Step 14440 directs the logic to step 14450 for low sensitivity and to step 14445 for high sensitivity. In one example, step 14440 selects low sensitivity for short strokes or partial strokes of the blood pump due to variability in short strokes of the blood pump. In a short stroke, the diaphragm is not driven against the inner wall of the pod pump. Instead, the delivery stroke is shortened. In some medical applications, a short delivery stroke can be beneficial to reduce damage to blood cells between the diaphragm 14025 and the wall of the pod pump 23a. Short strokes have greater variability; and to avoid false occlusion detection, low sensitivity occlusion testing in step 14450 can be preferred. In one example, step 14440 directs the logic to step 14445 for all non-short stroke operations.

[0215] With continued reference to Figure 66where, in step 14445, the occlusion algorithm 14400 compares the sum of pressure differences during the just completed stroke (dPSUM) to the sum of pressure differences for the last good stroke in the same direction (dPGOOD). In one example, occlusion is detected when two consecutive strokes in the same direction have a dPSUM less than 30% of the last good stroke (dPsum). More generally, occlusion is detected when a stroke has a dPSUM less than a predetermined fraction of the last good stroke (dPsum). In one example, occlusion is detected when more than two strokes have a dPSUM less than a predetermined fraction of the last good stroke (dPsum). If occlusion is detected, the logic moves to step 14470, where an occlusion warning or alarm is sent to the user interface (UI), and in one example, the pump can be stopped. In some embodiments, the UI indicates which pump and location of the inlet or outlet line that is occluded. If occlusion is not detected in 14445, the logic moves to step 14455.

[0216] Figure 66 The occlusion algorithm 14400 is summarized as including, in the low sensitivity step 14450, a comparison of the sum of pressure differences during the just completed stroke (dPSUM) to the sum of pressure differences for the last good stroke in the same direction (dPGOOD). In one example, occlusion is detected when three consecutive strokes in the same direction have a dPSUM less than 10% of the last good stroke (dPsum). In one example, occlusion is detected when a stroke has a dPSUM less than a second predetermined fraction of the last good stroke (dPsum). Alternatively, occlusion is detected when more than three strokes have a dPSUM less than a predetermined fraction of the last good stroke (dPsum). If occlusion is detected, the logic moves to step 14470, where an occlusion warning or alarm is sent to the user interface (UI), and in one example, the pump is stopped. In embodiments, the UI indicates which pump and location of the inlet or outlet line that is occluded. If occlusion is not detected in 14450, the logic moves to step 14455.

[0217] In step 14455, the controller 14035 detects an occlusion if either of the following occurs in one or more consecutive strokes in the same direction: less than a predetermined number of prime cycles occur, or the sum of pressure changes (dPsum) is less than a predetermined limit (dPsum limit). In one example, an occlusion is detected if either occurs in 3 consecutive strokes in the same direction. In another example, an occlusion occurs if either occurs in 2 consecutive cycles. In another example, the predetermined number of prime cycles is 5. In another example, the predetermined number of prime cycles is half the number of prime cycles in a typical stroke. If an occlusion is detected, the logic moves to step 14470, in which an occlusion warning or alarm is sent to the user interface (UI). In one example response, the pump is stopped. The controller can send data to the UI to indicate which pump is affected and whether the occlusion occurred in the inlet or outlet line. If no occlusion is detected in 14455, the logic moves to step 14460.

[0218] In step 14460, the controller 14035 detects an occlusion if the magnitude of the pressure in the actuation chamber 14020 is significantly greater than the target pressure for a predetermined period of time. In one example, step 14460 detects an occlusion if the magnitude of the pressure in the actuation chamber 14040 is greater than the target pressure by more than 60 mmHg for a predetermined period of time. In another example, the predetermined period of time in step 14460 is 25% of the stroke duration, which is the time from the start of the stroke to the EOS detection.

[0219] Partial obstruction detection

[0220] Partial occlusion can limit flow rate, but not block flow in the liquid line. Depending on whether a partial or complete occlusion is detected, the functionality of the hemodialysis machine can be modified and / or the message to the user can be changed. The controller detects partial occlusion based on the flow rate of the most recent stroke and the stroke target pressure for that most recent stroke. If the last stroke flow rate is below the desired flow rate, the pump controller changes the target pressure to achieve the desired flow rate and increases the target pressure for the next stroke. There is a maximum target pressure for a given pump, which can depend on the pressure reservoir pressure and / or the use of the given pump. In an example, partial occlusion can be indicated if the most recent flow rate through the pump has not reached the desired flow rate despite setting the target pressure for the most recent stroke to the maximum. In another example, partial occlusion can be indicated when the flow rate of the most recent stroke is less than 75% of the desired flow rate despite setting the target pressure for the most recent stroke to the maximum. In a hemodialysis system, the partial occlusion detection functionality can be applied to the blood pump to determine whether there is a problem with the positioning of the individual's vascular access or set of blood lines.

[0221] Blood flow metric

[0222] In embodiments, the controller can be programmed to provide an indication of the blood flow metric (mass or flow rate of blood from the venous access or arteriovenous fistula) to the user of the extracorporeal or hemodialysis system during each pump fill stroke. For example, the flow metric value can be communicated to a graphical user interface, providing the user with a continuous indication of the mass or adequacy of blood flow in the blood lines during treatment. The user interface, such as, for example, an electronic tablet, can provide the user with raw flow metric data. In another embodiment, the flow metric can be scaled proportionally to a range of 1 to 5, where, for example, a value of "5" indicates excellent flow, a value of "3" indicates marginal flow, and a value of "1" indicates occluded flow. Thus, a specified range of flow metric values can be mapped into each of the set values of "1" to "5," simplifying the user's explanation of the adequacy of blood flow in the blood lines. In other embodiments, the flow metric can be displayed to the user in a graphical manner, such as, for example, in the form of a moving or expanding bar graph, a dial, or a set of colored lights.

[0223] In preferred embodiments, a critical or suboptimal flow metric can cause the controller to alert the user so that the user can attempt to improve the blood flow in the blood line (e.g., reposition the line, straighten the line, adjust the vascular access cannula, etc.). The controller can be programmed to initiate a procedure to pause or stop the dialysate pump that includes signaling the user and providing sufficient time elapse before the pause or stop of the dialysate pump to allow the user to correct the condition. The user can be alerted to the low flow condition during the fill stroke so that the user’s timely adjustment allows the flow metric to return to an acceptable value before the end of the fill stroke. Alternatively, the controller can be programmed to allow suboptimal flow metric values for two or three (or more) consecutive fill strokes before commanding the dialysate pump to stop. Thus, the user’s timely correction of the low flow condition can prevent interruption of the dialysate pumping operation and possible interruption of treatment. In an example, the controller can be programmed to pause or stop the dialysate pump if the flow metric remains below 150 (e.g., dP / dt in mmHg / sec) for three consecutive fill strokes, and the controller can be programmed not to restart the dialysate pump until the flow metric exceeds 200 for five consecutive blood pump strokes. In some of these embodiments, the controller allows the blood pump to continue operation while the dialysate pump has been suspended so that the user has an opportunity to restore the blood flow condition that allows the dialysate pump to restart, thereby avoiding premature termination of treatment.

[0224] Referring now to Figure 60 and Figure 62 , the controller 14035 can determine a flow metric during a fill stroke based on the actuation chamber pressure while the pneumatic valve N1 is closed. The actuation chamber pressure is measured by a pressure sensor 196 in communication with the controller 14035. In one example, the controller 14035 can determine the flow metric based on a rate of change of the signal from the pressure sensor 196 while the valve N1 is closed. In another example, the controller 14035 can determine the flow metric based on a minimum rate of change of the actuation pressure during the stroke (i.e., the lowest or near lowest rate of pressure change detected by the controller) while the valve N1 is closed. In another example, the controller 14035 can determine the flow metric based on a minimum rate of change of the actuation pressure during the stroke that does not include the fill cycle that generates the end of stroke signal. In one example, a low pass filter is used to determine the rate of change of the actuation pressure during each fill cycle, and the minimum of the rate of change for each fill cycle is low pass filtered over the stroke to determine the flow metric.

[0225] Figure 67 The flow metric algorithm 14500 is illustrated in a flowchart that begins with the blood pump Figure 6023a) "Start Fill Stroke." Upstream valve 192 opens and downstream valve 193 closes. The fill stroke continues by opening pneumatic valve Nl in step 14515 and closing valve Nl in step 14520 to create a desired negative pressure or sub-ambient pressure in the actuation chamber 14020 of blood pump 23a. The negative pressure in actuation chamber 14020 draws blood from the access site through tube 203 into the pumping chamber of blood pump 23a. As the pump chamber fills and compresses the gas in actuation chamber 14020, the magnitude of the negative pressure in actuation chamber 14020 decreases. This decrease in negative pressure magnitude is sensed by pressure sensor 196 and communicated to controller 190 in step 14525 Figure 67) to the controller 14035. The controller analyzes the data and (optionally) determines the rate of change of pressure (dP / dt) in the actuation chamber using a low pass filter (LPF) function in step 14530. If the end of fill cycle has occurred, step 14535 directs the logic to step 14540 where the end of stroke (EOS) is determined. If the end of fill cycle has not occurred, then the logic is directed to continue monitoring the pressure signal 14525. If the EOS is not detected in step 14540, then the controller determines the minimum dP / dt magnitude at the time the valve Nl is closed in step 14545. The minimum or lowest dP / dt detected by the controller for the current fill cycle is then used in the LPF in step 14550 to update the minimum dP / dt for the fill stroke and then the valve Nl is reopened in step 14515 to start the next fill cycle. If the EOS is detected in step 14540, then the logic proceeds to step 14555 where the pod controller 14035 reports the minimum dP / dt to the controller which converts the minimum dP / dt value to a more easily understood indicator which is in turn displayed on a user interface (UI). The UI can be a graphical display unit such as a tablet computer. The indicator is a flow metric for the inlet blood line and accessway. In an example, the minimum dP / dt value is displayed as a value from 1 to 5 where 1 is a blocked accessway, 3 is a marginal accessway, and 5 is a free flowing accessway. Here, accessway means the system of needle or cannula, the placement of the needle or cannula, and flow restrictions at the inlet of the needle or cannula. In an example, for a minimum dP / dt less than 25 mmHg / s the flow metric is 1 or blocked, for a minimum dP / dt between 25 mmHg / s and 50 mmHg / s the flow metric is 2 or poor, for a minimum dP / dt between 50 mmHg / s and 75 mmHg / s the flow metric is 3 or marginal, for a minimum dP / dt between 75 mmHg / s and 100 mmHg / s the flow metric is 4 or good, and for a minimum dP / dt between 100 mmHg / s and 125 mmHg / s the flow metric is 5 or excellent. In addition to displaying the flow metric on the UI in step 14555, the flow metric algorithm 14500 also evaluates the flow metric in step 14560 and if the flow metric remains below a predetermined value for more than a predetermined number of strokes or a predetermined period of time, the flow metric algorithm 14500 alerts the user 14570. In an example, if three consecutive fill strokes have a dP / dt below a value of 50 mmHg / s, step 14560 indicates an alert in step 14570.In this case, the logic moves to the delivery stroke of the blood pump in step 14580 regardless of the flow metric or minimum dP / dt, and then the logic returns in step 14510 to start the fill stroke.

[0226] Connection to water purification device

[0227] A hemodialysis device or apparatus (HDD) can be configured to interact and communicate with a water purification device (WPD) that provides water to the HDD system for use in mixing dialysate solutions and for disinfecting the HDD before or after a dialysis treatment. In previous disclosures (see, e.g., U.S. Patent Application Publication No. US / 2016 / 0058933), a series of messages and data can be exchanged between one or more HDD controllers and a WPD controller. In a more streamlined approach, rather than relying on pre-programmed or autonomous functions of the WPD, the types of interactions between the two devices can be limited. In one example, the WPD can be a water vapor compression / distillation apparatus. Alternatively or in addition, other water purification devices and methods can be used, such as semi-permeable membrane filtration, reverse osmosis, ultraviolet irradiation, charcoal adsorption, or any combination of these methods.

[0228] The HDD controller can be configured to send a start signal to the WPD, the start signal representing a command to start production of normal temperature water, where the WPD proceeds according to its independently programmed processor. This is the mode typically used when purified water is being delivered to the HDD for dialysate mixing and treatment. The HDD controller can also send a start hot water command to the WPD, the start hot water command representing a command to start production of hot water according to a pre-programmed process of the WPD. This is the mode typically used to perform a disinfection program of the WPD. The lines connecting the WPD to the HDD (the water inlet lines of the HDD) and the HDD itself can be disinfected using operations programmed into one or more HDD controllers.

[0229] The HDD controller can also command the WPD to enter a standby mode or state, or an idle mode or state. In a water vapor compression / distillation apparatus, the idle state can involve pausing the pump or compressor, turning off the heater, closing the valves, and deactivating the control loops and level controller. The standby mode or state allows the WPD to produce purified water relatively quickly; and, optionally in a vapor / distillation system, this can include filling the purification system with water and heating the water to a point where purified water production can begin, controlling the exhaust valve to maintain a low pressure vapor temperature target, and optionally producing enough water to fill a reservoir, or alternatively, draining excess water produced. If the WPD starts from a non-enabled (off) state or an idle state, the HDD controller can optionally be programmed to send the command early enough to allow the WPD to produce water by the time the HDD expects to receive water delivery. (In some cases, this can total about 2 hours from a cold start or from an idle mode start, or only about 10 minutes from a standby mode start). In most cases, the HDD controller will command an idle WPD to enter a standby mode when the two systems establish communication, or when one or both systems restart after a power outage. This can not occur if an error state has been flagged.

[0230] During water delivery, the HDD controller can send a stop signal to the WPD, which commands the WPD to enter a standby state. In this case, the standby state is an autonomous function of the WPD that keeps water production or purification active enough to be able to deliver water on command from the HDD within a relatively short period of time (e.g., within about 10 minutes of the HDD sending a start or resume command to the WPD). In other operations, this can include filling the purification system with water and heating the water to a point where purified water production can quickly begin.

[0231] The HDD controller can also send a start disinfection command to the WPD, which is typically scheduled to occur after a dialysis treatment has ended or during a time between treatment sessions with the HDD. In this case, the WPD enters an automatic hot water production mode. In a typical sequence, the HDD first commands the WPD to enter a water production mode, and then once the WPD signals that it has entered the water production mode, the HDD commands entry into a disinfection mode. Once the water produced by the WPD reaches a specified temperature (e.g., 90 degrees Celsius), the HDD controller is signaled, and the HDD initiates an inlet line disinfection program. The inlet line includes the flow path within the HDD up to a branch point that connects the inlet line to the flow path leading to the outlet line or mixing loop of the HDD. (Beyond this branch point, the internal flow path of the HDD can be disinfected by a programmed circulation of hot water or chemical disinfectant without any "blind end"). This state also disinfects any tubing that connects the output port or line of the WPD to the input port or line of the HDD.

[0232] The controller of the HDD can be programmed to sterilize the WPD-HDD connection line and flow path for a predetermined minimum amount of time at a predetermined minimum temperature. For example, the sterilization temperature can be set to 85 degrees Celsius for a minimum of 35 minutes. This temperature can be measured by a temperature sensor located at the water inlet line of the HDD. To reduce the number of temperature sensors in the HDD system, the inlet water temperature sensor can preferably also be located in a position in the HDD flow path where the temperature of the sterilization fluid circulating through the HDD flow path during the sterilization of the HDD system can be monitored. Depending on the distance the incoming water travels before reaching the temperature sensor, the minimum sterilization temperature can optionally be adjusted to account for heat loss before the water reaches the sensor.

[0233] Figure 68 A schematic diagram of the fluid flow path for the hemodialysis system described in the prior application is shown. Section A represents the blood flow path of the system, section B represents the dialysate fluid balancing and dialyzer delivery section, section C represents the dialysate storage, heating and ultrafiltration section, and section D represents the water inlet and dialysate mixing section. The water inlet line 400 is configured to be externally connected to a water source. In the current embodiment, the water source includes a water purification device (WPD), such as a water vapor compression / distillation apparatus. For ease of reference, the inlet water line 400 is intended herein to represent the entire water line connection between the purified water outlet of the WPD and the point 402 at which the HDD inlet water line has a valve connection to the internal flow path of the HDD. In practice, this inter-device water line can include one or more connectors or valves. However, for sterilization purposes, the inlet water line 400 can be considered to include the entire inter-device water line.

[0234] While the internal fluid flow paths of the WPD and the internal fluid flow path of the illustrated HDD can be configured to enable a thorough and complete sterilization process, sterilization of the inlet water line connecting the WPD to the HDD and / or the inter-device line can require special attention. It should be noted that the inlet water line 400 has a valve connection 402 to the internal HDD flow path, and it should be noted that for the purposes of thorough sterilization, either chemical sterilization or heat sterilization, this inter-device fluid connection (WPD outlet line and HDD inlet line) becomes a blind end. This is also reflected in the outlet line of the WPD. While it is possible to use the HDD dialysate heater to heat water, which can then be pumped by one or more dialysate pumps in the opposite direction through the HDD inlet line, through the WPD outlet line, and thereby to the drain connection of the WPD, it can be more efficient to produce purified hot water (or water containing an appropriate chemical sterilizing agent) by the WPD and send it to the HDD in the normal forward direction, with the sterilizing liquid then being drained to the drain line 404 of the HDD.

[0235] Figure 69 A separate view of section D portion of the HDD system flow path is shown. Although a temperature sensor can be located in line 400, the temperature sensor will only be used to monitor the inflow water temperature. For disinfection purposes, the heated inflow water can be directed to the drain line 404 directly, but the flow path will depend on the action of the water pump located in the WPD. On the other hand, a temperature sensor 406 can be located in the internal line 408 connected to the water pump 410, which can then provide the pumping action required to move the water through lines 400 and 408. This sensor can also be used to monitor the liquid temperature during disinfection of the various internal flow paths in the HDD system. The heated liquid from section C in Figure 68 can be directed to the flow path in section D via water line 408. Figure 69 (see also Figure 68 ) The inlet line disinfection flow path including water pump 410 in the illustrated system can be directed through the conductivity / temperature sensors 412, 414 in the dialysate mixing path and thereby bypass the dialysate tank 416 by closing valve 418 and opening valve 420, leading to the drain line 404. It should be noted that in alternative embodiments, the monitoring of the temperature of the disinfection liquid can also be done using the existing temperature sensors already installed for the purpose of mixing dialysate, i.e. sensor 412 or sensor 414, without the need to add a temperature sensor in water inlet line 400 or 408. In all these cases, an active management valve or a passive check valve ensures that the disinfection liquid is directed to the drain line 404.

[0236] In embodiments, and as shown in Figure 70 the start of the disinfection procedure can first involve having the HDD command the WPD to start normal water production 450. Thereafter, the HDD starts priming of the flow path of the HDD with water from the WPD 452. The HDD then commands the WPD to produce water heated to the required disinfection temperature 454. Optionally, the WPD produces the heated water at a temperature higher than the minimum disinfection temperature specified for the lines interconnecting the WPD and the HDD. This is to account for heat loss of the water as it travels through the interconnecting lines. For example, if the minimum disinfection temperature is 85 degrees Celsius, then the WPD can be programmed to produce water at 90 degrees Celsius at the outlet of the WPD. Optionally, the HDD can be programmed to use the internal heater of the HDD (e.g. heater 430) to heat the water in the internal line 408 of the HDD to the required temperature. The heated water is then directed to the drain line 404. Figure 68The HDD can be programmed to initiate production of heated water 456 by the heater 411 in the WPD. This prepares the HDD to perform its own disinfection after the inter-device line 400 has been disinfected, and helps maintain a high ambient temperature in the HDD housing to limit heat loss during disinfection of the inter-device line 400. Once both the HDD and the WPD have heated their respective fluid flow paths to the specified temperature, the HDD controller can then command the WPD to begin delivering heated water from the WPD's product outlet line to the inter-device line (the inlet line 400) that connects the WPD to the HDD 458.

[0237] The water disinfection temperature can vary during the disinfection cycle. Optionally, the controller of the HDD can be programmed to track the amount of time during which the measured temperature reaches or exceeds a minimum disinfection temperature programmed into the controller.

[0238] As Figure 71 Optionally, as shown in FIG. 4B, before starting the disinfection counter for the inter-device line 400, the HDD controller begins controlling the internal HDD pump and associated valves to circulate heated inflow water from the WPD for a predetermined period of time 460, filling the disinfection flow path completely with heated water. In addition to the inter-device line, in one example, this flow path can include a flow path within the HDD that directs disinfection water through the water pump 410 in the mixing circuit, through the line leading to the dialysate tank 416 but diverted to the drain line 404 by one or more valves 418, 420 (see, e.g., FIG. 4A). Figure 69 In one example, the HDD controller directs heated water from the WPD to the HDD drain line for about 2 minutes before the inter-device line disinfection counter is started.

[0239] The HDD controller can be programmed to include a predetermined minimum disinfection temperature (e.g., 78 degrees Celsius). Once a temperature sensor (e.g., sensor 406 or sensors 412 or 414) detects this temperature, the controller starts a disinfection timer 462. If this minimum disinfection temperature is maintained for a predetermined minimum disinfection time (e.g., 35 minutes) 464, then the controller can indicate that disinfection of the inter-device line 400 is complete. The disinfection timer 464 is updated as long as the detected temperature is at or above the minimum disinfection temperature.

[0240] Optionally, the controller can be programmed to include a timer 466 that accumulates the amount of time that the detected temperature is less than the minimum sanitization temperature but greater than or equal to a predetermined low temperature threshold (e.g., 70 degrees Celsius). If a predetermined low temperature timeout value is reached (e.g., more than 10 minutes into the sanitization cycle), then the controller can signal a warning to the user interface and command the WPD to pause water production 468. Optionally, the controller can also be programmed to signal a warning and command the WPD to pause water production 468 if the detected temperature is less than the predetermined low temperature threshold (e.g., 70 degrees Celsius).

[0241] If the inter-device line 400 sanitizes successfully 470, then the HDD controller can close the inlet water line valve 402, command the WPD to begin the WPD's sanitization program, and initiate the HDD sanitization program. If the inter-device line 400 sanitizes unsuccessfully, then the user is notified and the WPD is commanded to pause water production 468. In these cases, the HDD controller optionally initiates a repriming program of the flow path of the HDD at 472 and resets the sanitization timer. The HDD controller can then wait for user input 474 to either reattempt the sanitization program or not reattempt the sanitization program. If the sanitization program is not reattempted, then the HDD can optionally initiate a service call 476. The controller can provide appropriate instructions to the user on the user interface, or the controller can be configured to automatically send appropriate messages to a remote server and service center via a network communication link.

[0242] The HDD controller can command the WPD to enter a flush mode in which source water flows into the system and through any filters in the system. This is typically performed after a filter change. If a filter (e.g., carbon filter) change is indicated, then the HDD controller can first command the WPD to enter an idle state, then signal a warning to the user on the graphical user interface that the WPD is ready for its filter to be changed. Once the user indicates that the task is complete, then the HDD can command the WPD to enter a standby state, then enter the flush mode. The HDD commands return to the standby state upon completion of the task so that the water production state can be quickly initiated at the start of a treatment. The flush mode can also be commanded prior to fluid sampling to ensure a more reliable indication of the quality of the filter. The flush mode can also be commanded if the WPD system is in an idle or standby state for more than a predetermined period of time.

[0243] State messages can be sent between the water layer of the HDD system controller architecture and the treatment layer of the HDD system controller architecture. Example messages that the water layer can receive from the WPD can include:

[0244] - the current operational state of the WPD

[0245] - an identification code or identifier of the current WPD

[0246] - the date the WPD filter was installed

[0247] - whether the filter needs to be replaced

[0248] - whether communication with the WPD has been lost

[0249] - whether the WPD indicates an operational error

[0250] - whether the WPD indicates a failsafe error

[0251] - the time since the WPD was last sanitized

[0252] - whether the WPD needs to be sanitized

[0253] - the software version installed on the WPD system controller

[0254] The status message about the operational status of the WPD can include one or more of the following:

[0255] - the WPD is enabled (independent of the HDD); the start of the communication link between the HDD and the WPD causes the HDD to command the WPD to enter a standby state.

[0256] - the WPD is idle; the product valve is closed.

[0257] - the WPD is in standby; the product valve is open.

[0258] - the WPD produces ambient temperature water; the product valve is open.

[0259] - the WPD is waiting for filter replacement; the product valve is closed.

[0260] - the WPD is flushing the line and filter after filter replacement.

[0261] - the WPD produces hot water; the product valve is open when at a certain temperature.

[0262] - the WPD is sanitizing; the product valve is closed.

[0263] - the WPD produces a water sample for testing (e.g., chlorine test); the product valve is closed.

[0264] - the WPD is waiting for user input in the GUI to deliver a water sample for testing.

[0265] - the WPD is in a failsafe state; the product valve is closed.

[0266] Preferably, the HDD controller commands the WPD to remain in standby mode at any time it is not performing other operations. If the WPD is in other operations (e.g., sanitization), the HDD controller waits for the operation to complete. Once the WPD is in standby mode, the HDD controller can check to see if the WPD should perform a filter flush operation. If so, the WPD initiates a filter flush operation. For example, if a power outage occurs after replacing a filter before a filter flush is completed, the HDD can also command a filter flush operation.

[0267] Optionally, prior to initiating water production for treatment, the HDD can be programmed to require the user to sample product water from the WPD to test for various contaminants, such as chloramines. The HDD can command the WPD to initiate a water sampling state. When the WPD indicates a ready state for sampling, the HDD alerts the user to collect and test the water sample. If the user indicates that the sample has passed testing, the HDD can subsequently command the WPD to begin water production for treatment. If the user indicates that the sample has failed testing, the HDD can optionally command the WPD to enter a standby state.

[0268] Errors from the WPD during water production can signal the HHD, which can subsequently send a command to acknowledge the error state and alert the user via an interface (e.g., the HDD interface). The WPD controller then waits for a command from the user to attempt to resume water production or transition to a standby state. A failsafe error state will typically cause the WPD operation to stop and signal the HDD to initiate a treatment termination procedure.

Claims

1. A manifold adapter configured to connect a pressure distribution manifold to a fluid handling cartridge assembly, the manifold adapter comprising: The housing has a first side portion including a first set of transmission ports configured to be connected to an actuation output port of the manifold, and the housing has an opposite second side portion including a second set of transmission ports configured to be connected to an actuation input port of the cartridge assembly. The first set of transmission ports includes a first spatial array configured to match the spatial array of the actuation output ports of the manifold; The second set of transmission ports includes a second spatial array configured to match the spatial array of the actuation input ports of the box assembly; The first spatial array of the transmission port is different from the second spatial array of the transmission port.

2. The manifold adapter according to claim 1, wherein, The first spatial array covers a region having a first length and a first width on the first side of the adapter housing, and the second spatial array covers a region having a second length and a second width on the second side of the adapter housing, wherein the second length is greater than the first length, such that the housing of the manifold adapter extends out of one side of the manifold.

3. The manifold adapter according to claim 1, wherein, The second side of the housing includes a resilient scraping washer, the scraping washer including a plurality of scraping seals, each of the plurality of scraping seals being associated with a second set of transmission ports on the second side of the adapter housing, wherein the scraping washer is embedded below the top plate of the adapter housing.

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