Liquid pumping cassette and associated pressure distribution manifold and associated method

Abstract

To provide improved methods for connecting a cassette assembly to a related pressure distribution manifold.SOLUTION: A fluid-handling cassette comprising a plurality of diaphragm valves and pumps is configured to have its actuation ports located along a thin or narrow edge of the cassette. Actuation channels within the cassette lead from the actuation ports to actuation chambers of the valves and pumps in a space between plates that form the cassette. The individual plates have a nominal thickness that is sufficient to provide a rigid ceiling for the actuation channels but sufficiently thin to minimize the overall thickness of the cassette. The cassette can be plugged into or unplugged from an actuation receptacle or a manifold by its narrow edge. A plurality of such cassettes can be stacked together or spaced to form a cassette assembly, providing a convenient way to cause the cassette assembly to be installed in and removed from its actuation receptacle.SELECTED DRAWING: Figure 6

Description

Technical Field

[0001] The present disclosure generally relates to improvements in the design and structure of fluid pumps or mixing cassettes, cassette assemblies, their components, and related devices.

Background Art

[0002] Fluid processing cassettes that include diaphragm pumps and / or valves can be actuated hydraulically (either hydraulically or pneumatically). In some examples, the cassette is designed to be fluidly connected to a pneumatically actuated manifold having electromechanical valves that selectively distribute positively or negatively pressurized gas or air to the cassette. A programmable electronic controller can be used to control the electromechanical valves to selectively supply positive or negative pneumatic pressure to various pumps or valves of the cassette in a predetermined manner.

[0003] Some fluid processing cassettes can have a substantially planar shape, with narrow or thin side faces adjacent to wider side faces, where the narrow or thin side faces have a thickness that is relatively small compared to the dimensions of the overall wider side face of the cassette. Liquid inlet and outlet ports can be incorporated into the ends or narrow side faces of the cassette. However, in many of these devices, the operating ports of the cassette are located on the face or wider side face of the cassette directly above the operating chamber of a controlled pump or valve. This generally provides the shortest routing within the cassette from the external cassette operating port to the operating chamber and diaphragm of a pump or valve within the cassette. Further, in many cases, the pumping station or valve station or region of the cassette (including either the operating chamber on one side or the liquid conveyance chamber on the opposite side) can be formed by a spherical or hemispherical chamber wall that extends above the plane of the cassette face, which in some applications can make the overall cassette thicker than desired. In other cases, the pump module can include a pneumatic or fluid passage embedded within one or more blocks or can include a stack of blocks that are sandwiched or laminated together with the passage. This configuration can also result in an overall device thickness that is larger than desired for a particular application. In some applications, it may be necessary to mount multiple fluid processing cassettes adjacent to each other in a narrow space. In these cases, it may be desirable to arrange multiple cassettes adjacent to each other, stack them on top of each other, or at least position their wider side faces in close proximity facing each other. It may be particularly desirable to reduce or minimize the thickness of the individual cassettes that make up these assemblies.

[0004] It may be advantageous to configure the pump cassette to plug directly into its associated pressure distribution manifold (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 hemodialysis systems that use pneumatically actuated self - contained pump cassettes, the pump cassettes are connected to the corresponding pneumatic manifolds via flexible tubes, which has presented significant problems during assembly and their operation. If the pump cassette can be placed in the vicinity of its associated manifold, there are significant advantages to a direct plug - in connection between the two. Under these circumstances, it is particularly advantageous to have a compact manifold that enables a direct interface to the pump cassette, arranged such that the cassette or cassette assembly can be plugged into and withdrawn from the operating ports of the manifold with minimal effort.

[0005] In the design and operation of the pneumatic distribution manifold, it is also of great advantage in both cost and reliability that binary pressure control valves can be used instead of continuously variable orifice valves. However, in this case, controlling the pressure supply to individual cassette pumps or valves by binary pressure control valves presents additional challenges that must be overcome. A sufficiently robust electronic controller can be programmed to use control algorithms to control the cycle and duration of binary valve actuation to achieve accurate control of the associated pneumatically actuated pumps or valves. SUMMARY OF THE INVENTION

[0006] In one embodiment, the pump and / or valve cassette has a relatively planar shape with a wide side adjacent to a thinner and narrower side or end. The pump and / or valve cassette includes an intermediate plate disposed between two outer plates. The first outer plate faces a first side of the intermediate plate, and the second outer plate faces a second side of the intermediate plate opposite the first side. The first outer plate is spaced from the intermediate plate to form a first interplate space. The second outer plate is spaced from the intermediate plate to form a second interplate space. The thicknesses of the first and second outer plates are limited to a thickness sufficient to provide rigidity to the plates and a sealing surface for the opposing passage walls on both sides of the intermediate plate. In some embodiments, the thickness of each outer plate, along with the thickness of the intermediate plate therebetween, defines the overall thickness of the cassette. In other embodiments, the liquid inlet and outlet ports project from the outer surface of the cassette, thereby increasing 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 and size of the pump or valve stations can determine the dimensions of the overall wide side of the cassette. The stroke volume of the on-board pump is a function of the diameter of the diaphragm associated with the pump station and the depth of the range of movement of the diaphragm defined by the depth of the passage walls of the intermediate plate, thereby determining the thickness of the cassette and the dimensions of its wide side. For any given pump or valve station, the intermediate plate includes a working side and an opposite liquid side, and the working side holds the pump diaphragm or valve diaphragm. The working passages in the cassette to the individual pump or valve stations are housed within the intermediate plate passages of the first interplate space and can extend generally parallel to the wide side of the cassette. The liquid passages in the cassette are housed within the intermediate plate passages of the second interplate space and generally extend parallel to the wide side of the cassette, except in some cases where the liquid passage connects to the inlet or outlet of the cassette.In this configuration, the first and second outer plates mainly function to provide a roof or a limiting wall over the individual actuation and liquid conveyance valve or pump regions.

[0007] In one embodiment, the fluid processing cassette may include an intermediate plate disposed between a first plate and a second plate, the plates having a length, a width, and a thickness of the plate, a first side of the intermediate plate facing the first plate, and a second side of the intermediate plate facing the second plate. The first plate is spaced apart from the intermediate plate that defines the width of the first plate space, and the second plate is spaced apart from the intermediate plate that defines the width of the second plate space. The end of the cassette has a cassette thickness defined by adding the width of the first and second plate spaces to the thickness of each plate, and the face of the cassette is defined by the length and width of the first or second plate. The intermediate plate can include a pump station formed by the pump diaphragm and the first side of the intermediate plate, the pump diaphragm seating against the first side of the intermediate plate and having a range of motion defined by the width of the first plate space. The pump actuation passage extends parallel to the face of the cassette within the first plate space, and the pump actuation passage connects a pump actuation chamber bounded by the first plate and the pump diaphragm to a cassette pump actuation port disposed at a first end of the cassette within the first plate space. The first and second pump fluid ports within the pump station can fluidly connect individual first and second fluid passages of the second plate space to a pumping chamber formed by the pump diaphragm and the first side of the intermediate plate. The pump fluid port within the pump station can fluidly connect the fluid passage of the second plate space to a pumping chamber formed by the pump diaphragm and the first side of the intermediate plate. Alternatively, an opening may be provided in the intermediate plate at the pump station, the opening allowing the pump diaphragm to move from the first plate to the second plate when actuated by a positive or negative pressure supplied through the pump actuation passage. The plates (first, intermediate, and second) have a thickness insufficient to allow fluid passages or actuation passages to travel within the plate in a direction parallel to the face of the cassette.The fluid passage extends into the space between the second plates and can be fluidly connected to a pumping chamber formed by the pump diaphragm and the first side surface of the intermediate plate. The connection is made through one or more pump fluid ports in the intermediate plate. The fluid passage extends parallel to the surface of the cassette within the space between the second plates. The fluid passage connects the pumping chamber to a cassette fluid port disposed at the first or second end of the cassette within the space between the second plates.

[0008] In one embodiment, the fluid processing cassette may include an intermediate plate disposed between a first plate and a second plate, the plates having a length, a width, and a thickness of the plate, a first side of the intermediate plate facing the first plate, and a second side of the intermediate plate facing the second plate. The first plate is spaced apart from the intermediate plate defining the width of the space between the first plates, and the second plate is spaced apart from the intermediate plate defining the width of the space between the second plates. The end of the cassette has a cassette thickness defined by adding the width of the space between the first and second plates to the thickness of each plate, and the face of the cassette is defined by the length and width of the first or second plate. The intermediate plate may include a valve diaphragm and a valve station formed by the first side of the intermediate plate, the valve diaphragm seating against the first side of the intermediate plate and having a range of motion defined by the width of the space between the first plates. The valve actuation passage extends parallel to the face of the cassette within the space between the first plates, the valve actuation passage connecting a valve actuation chamber bounded by the first plate and the valve diaphragm to a cassette valve actuation port disposed at the first end of the cassette within the space between the first plates. The first and second valve fluid ports within the valve station may fluidly connect the respective first and second fluid passages of the space between the second plates to a valve fluid chamber formed by the valve diaphragm and the first side of the intermediate plate. One or both of the valve fluid ports may include a raised valve seat for sealing the valve diaphragm over the first or second valve fluid port when positive pressure is applied to the valve diaphragm via the valve actuation passage. The first fluid passage is fluidly isolated from the second fluid passage other than via the first and second valve fluid ports.The fluid passage extends into the space between the second plates and can be fluidly connected to a valve fluid chamber formed by the valve diaphragm and the first side surface of the intermediate plate. The connection is made via two valve fluid ports in the intermediate plate. The fluid passage extends parallel to the surface of the cassette within the space between the second plates. The fluid passage connects the valve fluid chamber to a cassette fluid port disposed at a first end or a second end within the space between the second plates.

[0009] In another embodiment, the fluid processing cassette may include an intermediate plate disposed between a first plate and a second plate, the plates having a length, a width, and a thickness of the plate, a first side of the intermediate plate facing the first plate, and a second side of the intermediate plate facing the second plate. The first plate is spaced apart from the intermediate plate that defines the width of the first plate space, and the second plate is spaced apart from the intermediate plate that defines the width of the second plate space. The ends of the cassette have a cassette thickness defined by adding the width of the first and second plate spaces to the thickness of each plate, and the face of the cassette is defined by the length and width of the first or second plate. The intermediate plate may include a pump station formed by the pump diaphragm and the first side of the intermediate plate, the pump diaphragm seating against the first side of the intermediate plate and having a range of movement defined by the width of the first plate space. The intermediate plate may include first and second valve stations each formed by a valve diaphragm and the first side of the intermediate plate, the valve diaphragm seating against the first side of the intermediate plate and having a range of movement defined by the width of the first plate space. A pump actuation passage for the pump station and valve actuation passages for each of the first and second valve stations are provided. The pump actuation passage extends parallel to the face of the cassette within the first plate space, and the pump actuation passage connects a pump actuation chamber bounded by the first plate and the pump diaphragm to a cassette pump actuation port disposed at the first end of the cassette within the first plate space. Each of the valve actuation passages extends parallel to the face of the cassette within the first plate space, and each of the valve actuation passages connects a valve actuation chamber bounded by the first plate and the valve diaphragm to a cassette valve actuation port disposed at the first end of the cassette within the first plate space.Inlets and outlet valve fluid ports may be provided at each of two valve stations, one or more pump fluid ports may be provided at the pump station, and each of the valve and pump fluid ports fluidly connects a fluid passageway within the second plate space to a pumping chamber formed by the first face of the pump diaphragm and the intermediate plate, and to a valve fluid chamber at each valve station formed by the first face of the corresponding valve diaphragm and the intermediate plate. The fluid passageway has a flow path passing through the inlet and outlet valve fluid ports and the one or more pump fluid ports, and each of the valve actuation passages of the pump actuation chamber and the valve actuation chamber allows, by selective actuation, a one-way flow of fluid through the fluid passageway. The fluid passageway extends within the second plate space and is fluidly connected to the pumping chamber formed by the first side surfaces of the pump diaphragm and the intermediate plate, the connection being made via the pump fluid port in the intermediate plate, and the fluid passageway is fluidly connected to the valve fluid chamber of each valve station formed by the first side surfaces of the corresponding valve diaphragm and the intermediate plate, each connection being made via two valve fluid ports in the intermediate plate such that the fluid passageway extends parallel to the face of the cassette within the second plate space and such that the fluid passageway connects the pumping chamber and each valve fluid chamber to a cassette fluid inlet port and a cassette fluid outlet port disposed at the first or second end of the cassette within the second plate space. The cassette fluid inlet port and the cassette fluid outlet port are disposed at the second end of the cassette such that the cassette pump actuation port and the cassette valve actuation port are configured to be directly inserted into mating actuation receptacles external to the cassette, and such that the fluid inlet port and the fluid outlet port are arranged to be connected via a flexible or malleable tube to a fluid source or a fluid destination external to the cassette.The fluid passage extends into the space between the second plates and is fluidly connected to the pumping chamber formed by the pump diaphragm and the first side of the intermediate plate, the connection being made via the pump fluid ports in the intermediate plate. The fluid passage is fluidly connected to the valve fluid chambers of each valve station, each valve fluid chamber being formed by the corresponding valve diaphragm and the first side of the intermediate plate, and each connection being made via two valve fluid ports in the intermediate plate. The fluid passage extends parallel to the face of the cassette into the space between the second plates, connecting the pumping chamber and each valve fluid chamber to the cassette fluid inlet port and the cassette fluid outlet port, the cassette fluid inlet port and the cassette fluid outlet port emerging from the cassette via rigid conduits passing through the face of the cassette so as to pass through the first or second outer plate starting from the intermediate plate.

[0010] In a further embodiment, a plurality of walls may be formed on the first and second sides of the intermediate plate, and the walls are arranged to combine with the first and second plates within the cassette to form an actuation passage or a fluid passage. The first type of wall may include parallel walls that define an actuation passage or a fluid passage, the second type of wall may include a circumferential peripheral wall that defines a pump actuation station or a valve actuation station, and the third type of wall may include adjacent end walls that define a passage end where a valve fluid port or a pump fluid port penetrates the intermediate plate. The first plate may include one or more circumferential valve or pump diaphragm holders configured to fit within the circumferential peripheral wall of the opposing intermediate plate that defines a pump actuation station or a valve actuation station, and the holder is arranged to clamp the peripheral bead or rim of the associated diaphragm disposed within the pump or valve station of the intermediate plate. The holder may include holes, perforations, or slots to enable the transfer of actuation fluid or gas between the actuation passage associated with the valve or pump actuation chamber surrounded by the holder. The first plate includes elongated ribs configured to be disposed within the mating actuation passage of the intermediate plate, and the cross-sectional size and length of the ribs are determined to adjust the volume of the actuation passage to a predetermined value between the actuation port of the cassette and the valve or pump actuation chamber associated therewith.

[0011] In another embodiment, the fluid processing cassette may include an intermediate plate disposed 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 facing the first plate, a second side of the intermediate plate facing the second plate, the first plate being spaced apart from the intermediate plate defining the width of the first plate space, and the second plate being spaced apart from the intermediate plate defining the width of the second plate space. The ends of the cassette have a cassette thickness defined by adding the width of the first and second plate spaces to the thickness of each plate, and the face of the cassette is defined by the length and width of the first or second plate. The intermediate plate includes first and second valve stations, the first valve station being formed by a first valve diaphragm and the first side of the intermediate plate, the second valve station being formed by a second valve diaphragm and the second side of the intermediate plate, the first valve diaphragm seating on the first side of the intermediate plate and having a range of movement defined by the width of the first plate space, and the second valve diaphragm seating on the second side of the intermediate plate and having a range of movement defined by the width of the second plate space. A first valve actuation passage for the first valve station extends parallel to the face of the cassette within the first plate space, and a second valve actuation passage for the second valve station extends parallel to the face of the cassette within the second plate space. The first valve actuation passage connects a first valve actuation chamber bounded by the first plate and the first valve diaphragm to a first cassette valve actuation port disposed at a first end of the cassette within the first plate space, and the second valve actuation passage connects a second valve actuation chamber bounded by the second plate and the second valve diaphragm to a second cassette valve actuation port disposed at a first end of the cassette within the second plate space.

[0012] In another embodiment, the fluid processing cassette may include an intermediate plate disposed between a first plate and a second plate, the plates having a length, a width, and a thickness of the plate, a first side of the intermediate plate facing the first plate, and a second side of the intermediate plate facing the second plate. The first plate is spaced apart from the intermediate plate that defines the width of the space between the first plates, and the second plate is spaced apart from the intermediate plate that defines the width of the space between the second plates. The end of the cassette has a cassette thickness defined by adding the width of the spaces between the first and second plates to the thickness of each plate, and the face of the cassette is defined by the length and width of the first or second plate. The intermediate plate includes first and second pump stations, the first pump station being formed by the first pump diaphragm and the first side of the intermediate plate, the second pump station being formed by the second pump diaphragm and the second side of the intermediate plate, the first pump diaphragm seating on the first side of the intermediate plate and having a range of motion defined by the width of the space between the first plates, and the second pump diaphragm seating on the second side of the intermediate plate and having a range of motion defined by the width of the space between the second plates. The first pump actuation passage for the first pump station extends parallel to the face of the cassette within the space between the first plates, the second pump actuation passage for the second pump station extends parallel to the face of the cassette within the space between the second plates, the first pump actuation passage connecting a first pump actuation chamber bounded by the first plate and the first pump diaphragm to a first cassette pump actuation port disposed at a first end of the cassette within the space between the first plates. The second pump actuation passage connects a second pump actuation chamber bounded by the second plate and the second pump diaphragm to a second cassette pump actuation port disposed at a first end of the cassette within the space between the second plates.

[0013] In another embodiment, the fluid processing cassette assembly may include an intermediate cassette interposed between a first outer cassette and a second outer cassette, each cassette including an intermediate plate disposed between a first plate and a second plate, the plates having a length, a width, and a thickness of the plate, a first side of the intermediate plate facing the first plate, and a second side of the intermediate plate facing the second plate. The first plate is spaced apart from the intermediate plate defining the width of the space between the first plates, and the second plate is spaced apart from the intermediate plate defining the width of the space between the second plates. The ends of the cassette have a cassette thickness defined by adding the width of the spaces between the first and second plates to the thickness of each plate, and the faces of the cassette are defined by the length and width of the first or second plate. A plurality of diaphragm valves or pumps, including valve or pump actuation chambers, are connected to actuation passages that extend parallel to the face of the cassette within the space between the first or second plates and terminate within individual cassette valve or pump actuation ports at a first end of the cassette between the spaces of the first or second plates. The fluid processing pod is disposed in the space between cassettes between the intermediate cassette and the first or second cassette, and the pod has a fluid connection to a fluid passage within the intermediate, first, or second cassette via a fluid conduit that penetrates the face of the intermediate, first, or second cassette. The first ends of the intermediate, first, and second cassettes are disposed on a first side of the cassette assembly such that the cassette valve or pump actuation port is configured to be inserted into or withdrawn from an actuation port receptacle assembly that faces the first side of the cassette assembly. The fluid processing pod may include a diaphragm pump pod having an actuation and fluid connection to an actuation passage and a fluid passage within the intermediate, first, or second cassette via an actuation conduit and a fluid conduit that penetrate the face of the intermediate, first, or second cassette. The actuation conduit of the diaphragm pump pod connects to an actuation passage within the space between the first and second plates of the intermediate, first, or second cassette and has a continuous connection to a cassette actuation port for the diaphragm pump pod at the first end of the intermediate, first, or second cassette.The fluid conduit of the diaphragm pump pod is connected to a fluid passage within the space between the first and second plates of the intermediate, first, or second cassette and is connected to a diaphragm valve within the cassette. The actuation passage of the diaphragm valve may be connected to a cassette actuation port for the diaphragm valve at the first end of the intermediate, first, or second cassette. The fluid conduit in any of these configurations may be rigid. A plurality of fluid processing pods may be disposed 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 may be rigid to provide structural support for the cassette assembly. The cassette assembly frame can be configured to enhance the structural rigidity of the cassette assembly. The cassette assembly frame includes a rigid support plate on a second side of the cassette assembly opposite a first side of the cassette assembly, and the support plate is configured to engage a cassette loading device on the side opposite the actuation port receptacle.

[0014] In another embodiment, the fluid processing cassette assembly can include an intermediate cassette interposed between a first outer cassette and a second outer cassette, each cassette including an intermediate plate disposed between a first plate and a second plate, the plates having a length, a width, and a thickness of the plate, a first side of the intermediate plate facing the first plate, and a second side of the intermediate plate facing the second plate. The first plate is spaced apart from the intermediate plate defining the width of the space between the first plates, and the second plate is spaced apart from the intermediate plate defining the width of the space between the second plates. The end of the cassette has a cassette thickness defined by adding the width of the space between the first and second plates to the thickness of each plate, and the face of the cassette is defined by the length and width of the first or second plate. A plurality of diaphragm valves or pumps can include valve or pump actuation chambers connected to actuation passages, the actuation passages extending parallel to the face of the cassette within the space between the first or second plates and terminating at individual cassette valve or pump actuation ports at a first end of the cassette between the spaces between the first or second plates. A first fluid processing pod can be disposed in the inter-cassette space between the intermediate cassette and the first or second cassette. The fluid processing pod has a fluid connection to a fluid passage within the intermediate, first, or second cassette via a fluid conduit passing through the face of the intermediate, first, or second cassette. A second fluid processing pod can include a diaphragm pump pod having an actuation and fluid connection to an actuation passage and a fluid passage within the intermediate, first, or second cassette via an actuation conduit and a fluid conduit passing through the face of the intermediate, first, or second cassette. The first ends of the intermediate, first, and second cassettes are disposed on a first side of the cassette assembly such that the cassette valve or pump actuation port is configured to be inserted into or withdrawn from an actuation port receptacle assembly facing the first side of the cassette assembly.The actuating conduit of the diaphragm pump pod is connected to the actuating passage within the space between the first and second plates of the intermediate, first, or second cassette and may have a continuous connection to the cassette actuating port for the diaphragm pump pod at the first end of the intermediate, first, or second cassette. The fluid conduit of the diaphragm pump pod is connected to the fluid passage within the space between the first and second plates of the intermediate, first, or second cassette and is connected to the diaphragm valve within the cassette. The actuating passage of the diaphragm may be connected to the cassette actuating port for the diaphragm valve at the first end of the intermediate, first, or second cassette. The fluid conduit may be rigid. A plurality of fluid processing pods may be provided between the intermediate cassette and the first cassette and between the intermediate cassette and the second cassette. The associated fluid conduits of the plurality of fluid processing pods may be rigid to provide structural support for the cassette assembly. The cassette assembly frame can be configured to enhance the structural rigidity of the cassette assembly. The cassette assembly frame includes a rigid support plate on the second side of the cassette assembly opposite the first side of the cassette assembly. The support plate is configured to engage a cassette loading device on the side opposite the actuating port receptacle.

[0015] In another aspect of the invention, the manifold adapter is configured to connect a pressure distribution manifold to a fluid processing cassette assembly. The housing has a first side including a first set of transfer ports configured to connect to the operative output ports of the manifold, and an opposite second side including a second set of transfer ports configured to connect to the operative input ports of the cassette assembly. The first set of transfer ports includes a first spatial array configured to match a spatial array of the operative output ports of the manifold. The second set of transfer ports includes a second spatial array configured to match a spatial array of the operative input ports of the cassette assembly, and the first spatial array of transfer ports is different from the second spatial array of transfer ports. The first spatial array may cover a region having a first length and a first width of the first side of the adapter housing, and the second spatial array may cover a region having a second length and a second width of the second side of the adapter housing. The second length is greater than the first length such that the housing of the manifold adapter projects from the side of the manifold. The second side of the housing may include an elastomeric wiper gasket comprising a plurality of wiper seals, each of the plurality of wiper seals being associated with a transfer port on the second side of the adapter housing. The wiper gasket may be embedded under the upper plate of the adapter housing.

[0016] In another aspect, the seating device is described for use with a cassette having a plug-in side and an opposite mounting side. The seating device includes a fixed frame member connected to a movable cassette mount by a plurality of link mechanisms on a first side of the cassette mount and on a second side opposite the first side of the cassette mount. The link mechanism on the first side of the cassette mount is connected to a first fixed flange of the fixed frame member, and the link mechanism on the second side of the cassette mount is connected to a second fixed flange of the fixed frame member. Each of the plurality of link mechanisms may include a swing arm having a first end pivotally coupled to the fixed flange and a second end coupled to an elongated slot of the cassette mount. The second end of the swing arm is configured to move in an arcuate path to move the cassette mount such that the elongated slot restricts the movement of the cassette mount by the swing arm to linear movement toward or away from the fixed frame member. The cassette mount may include a first movable flange and a first rail on a first side of the cassette mount, and may include a second movable flange and a second rail on a second side of the cassette mount. Each of the movable flanges may have a surface substantially parallel to the 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 the first and second rails are configured to hold the mounting side of the cassette. The handle assembly is pivotally connected to the cassette mount such that when the handle of the handle assembly moves away from the fixed frame member, the cassette mount moves away from the fixed frame member, and when the handle moves toward the fixed frame member, the cassette mount moves toward the fixed frame member.The pivotal connection of the handle assembly may include a first pivotal connection of the first handle arm to the first fixed flange, a second pivotal connection of the second handle arm to the second fixed flange, a third pivotal connection to a handle swing arm connected to the first movable flange of the cassette mount of the first handle arm, and a fourth pivotal connection to a handle swing arm connected to the second movable flange of the cassette mount of the second handle arm. The first and third pivotal connections and the second and fourth pivotal connections may be spaced apart from each other on the first and second handle arms. The third fixed flange of the fixed frame member may face the handle assembly and be substantially perpendicular to the first and second fixed flanges. The handle assembly may include a spring-loaded plunger configured to engage a hole or recess in the third fixed flange such that the cassette mount is locked in the storage position when the handle of the handle assembly moves toward the fixed frame member.

Brief Description of the Drawings

[0017] Non-limiting embodiments of the present invention will be described by way of example with reference to the accompanying drawings, some of which are schematic and not intended to be drawn to scale. In the figures, each identical or substantially identical component shown is usually represented by a single number. For clarity, not all components are labeled in all figures, and not all components of each embodiment of the invention are shown where illustration is not necessary for a person skilled in the art to understand the invention.

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DETAILED DESCRIPTION OF THE INVENTION

[0018] Cassette with liquid passage and pneumatic passage in the plane In some pumping applications, it is advantageous to dispose the working ports of a fluid pressure or pneumatic actuated pump or valve cassette at the end, thin side, or narrow side of the cassette rather than at the wide side of the cassette. This allows the cassette to be inserted into a receptacle including an array of working ports associated with a pressure supply manifold at the narrow side rather than at the wide side. Thereby, the functions that a pump / valve cassette can perform within a limited space can be maximized. Depending on the situation, due to the overall space constraints, it may be advantageous to minimize the total thickness of the cassette. This can be achieved by making the cassette minimally thicker than the movable range of a hermetic diaphragm. Ideally, each outer plate of the cassette mainly functions as a roof or end wall of a pump or valve actuation or liquid conveyance chamber or passage, and its thickness is insufficient to completely enclose any liquid passage or actuation passage extending substantially parallel to the face or wide side of the cassette. The actuation passage is configured to extend within the space between an intermediate plate and an outer plate (e.g., the first outer plate) of the cassette within the space between plates defining the maximum movable range of one or more diaphragms of the cassette. The width of the space between the plates (and thus the maximum movable range of the flexible membrane or diaphragm) can be predetermined by the height of the passage walls formed on the actuation side and / or liquid conveyance side of the cassette intermediate plate. The height of the passage walls on one side of the intermediate plate can be different from the height of the passage walls on the opposite side of the intermediate plate. For example, to accommodate a desired fluid flow rate, the passage walls on the liquid side of the intermediate plate can be made higher to provide a larger cross-sectional area of the liquid conveyance passage, while the cross-sectional requirements (and thus the height of the passage walls) of the actuation passage on the actuation side of the intermediate plate can be smaller.

[0019] Figures 1A and 1B schematically show in cross-section the cassette 10 near the end of the filling stroke and near the end of the delivery stroke, respectively. The intermediate plate 12 is disposed between the first outer plate 14 and the second outer plate 16. The flexible diaphragm 18 is disposed within the first plate space 20, and the liquid flow path is present within the second plate space 22. To reduce the thickness of the pump and / or valve cassette, any actuation passage preferably extends into the first plate space 20, which is a space defined by the depth, movement depth, or linear range E of the movable range in which the diaphragm moves between the intermediate plate 12 and the first outer plate 14. In the case of an on-board diaphragm pump, its stroke volume is correlated with the depth of the movable range E of the diaphragm 18 and the effective surface area occupied by the diaphragm on the broad side of the cassette. The preferred depth of the movable range E of the diaphragm may also depend on how efficiently the stroke volume of the diaphragm can be increased by increasing its effective surface area. In this embodiment, two pump chamber liquid ports 24a, 24b representing the inlet and outlet are shown, each port being connected to a separate fluid passage within the plate space 22, and the fluid passages are schematically separated by the wall 38 (the direction of the liquid flow shown is arbitrary and depends on which liquid line is open or closed by the downstream valve during the filling or delivery stroke of the diaphragm). In another embodiment, as shown in FIGS. 2A and 2B, a single pump chamber liquid port 24c (or more than two such ports) can be used, and the pump chamber liquid port 24c alternates between an inlet port and an outlet port depending on which downstream valve is open or closed in a single liquid line within the plate space 22. When the volume of the actuation chamber 26 is at a minimum, the corresponding pump chamber 28 is at a maximum (see the filling stroke, FIGS. 1A and 2A). When the volume of the actuation chamber 26 is at a maximum, the volume of the corresponding pump chamber 28 is at a minimum (see the delivery stroke, FIGS. 1B and 2B).When the depth E of the movable range of the diaphragm on the cassette is selected, the thickness T of the cassette can be reduced by avoiding placing the actuating port directly above the actuated diaphragm (as in the prior art design). This is achieved by placing the actuating port on the thin or narrow side of the cassette and extending the actuating passage to the individual diaphragms within the first plate-to-plate space 20 within the cassette 10. This space is defined by an intermediate plate 12 on which the diaphragm 18 seats and a first outer plate 14 that provides a cover or roof for the actuating chamber 26 for each diaphragm 18. Surrounding each diaphragm is a wall 30 that spans the plate-to-plate space 20. The wall 30, together with the outer plate 14, completes each actuating chamber 26 except for the actuating port or actuating window 32 that connects the actuating chamber 26 to its corresponding actuating passage (represented by the arrow within the first plate-to-plate space 20). The actuating passage extends within the plate-to-plate space 20 to the outer peripheral end or narrow side of the cassette, where it terminates as a cassette actuating port (see, for example, FIG. 9). Note that the actuating passage can be made smaller than the depth provided by the plate-to-plate space 20, depending on what depth of movable range E is specified for the diaphragm 18. To minimize the overall thickness T of the cassette 10 for a given specified depth E of the movable range of the diaphragm, the nominal thickness P of each of the plates 12, 14, 16 can be minimized (within the constraints of structural rigidity and any constraints imposed in achieving proper welding or adhesion of the outer plate to the passage walls of the intermediate plate). Depending on the requirements of the fluid flow rate, the thickness of the cassette can also be minimized by reducing the depth (i.e., the height of the passage walls) of the liquid flow path within the second plate-to-plate space 22.

[0020] The overall thickness T of the cassette depends on the amount of depth required by the liquid flow path or liquid passage on the opposing side of the intermediate plate 12 of the cassette 10 within the second plate-to-plate space 22. FIGS. 1A - FIG 2BIn the pump shown in FIG. 2 and the valve shown in FIGS. 3A and 3B, the depth of the second inter-plate space 22 is determined by the required depth of the liquid passage. Depending on the liquid flow rate specified for the cassette, the second inter-plate space 22 may have a depth L that is substantially smaller than the depth E of the first inter-plate space 20.

[0021] As shown in FIGS. 3A and 3B, for any given diaphragm valve station, there are at least two liquid passages (a first passage terminating at valve port 34a of intermediate plate 12 and a second passage terminating at valve port 34b of intermediate plate 12) (in some embodiments, multiple liquid passages can terminate at separate valve ports in the intermediate plate of a single valve station). As shown in FIGS. 3A and 3B, the depth E of the range of motion is determined by the degree of relaxation necessary to allow the diaphragm 18 to lift away from the fluid ports 34a, b, which are designed to be blocked in the case of a diaphragm valve. The valve diaphragm 36 can move away from ports 34a, b under negative operating pressure as shown in FIG. 3A to allow liquid flow, or move to block ports 34a, b under positive operating pressure as shown in FIG. 2B to block liquid flow. The separate liquid passages within the valve station of the cassette are schematically represented by wall 38 shown within the second plate space 12. In the illustrated example, valve ports 34a, b can optionally include a raised element 40 (circumferentially disposed around the valve port) to improve the sealing efficiency of the diaphragm. Such a raised element may be required to be present only around one of the valve ports to be effective. Thus, when the valve diaphragm relaxes or is pulled away from the liquid ports of the valve, liquid can flow into the liquid valve chamber from one liquid passage through its associated port and then out through the liquid port of the second liquid passage connected to that valve station. The selection of the cross-sectional area of the liquid passage can depend on the desired liquid flow resistance and the desired hold-up volume or dead space occupied by the liquid passage within the cassette. The desired cross-sectional area of the liquid passage determines the depth (or height of the passage wall) of the liquid passage that occupies the second plate space 22 between the intermediate plate 12 and the second outer plate 16 of the cassette. The liquid passages and the actuation passages can be formed from the intermediate plate or individual outer plates or can be formed independently of the outer plates or intermediate plate.In a preferred configuration, the intermediate plate, together with the desired passage walls on both sides of the intermediate plate, is formed by molding, 3D printing, or casting otherwise, so that the structure of the outer plate can be simplified. The outer plate 14 may include the roof of the working chamber 26 or the diaphragm limiting wall, and the outer plate 16 may include the roof or the liquid passage within the cassette. In this way, the plate - to - plate space between the intermediate plate and the outer plate can be further reduced.

[0022] Accordingly, as shown in FIG. 1A, in a preferred embodiment, the thickness T of the pump or valve cassette 10 can be defined by adding the nominal thickness P of each of the intermediate plate and the two outer plates, the depth E of the movable range of the diaphragm 18, and the depth L of the liquid passage formed by the second plate - to - plate space 22 provided on the cassette. To maximize the efficiency of positioning and distributing valve and pump stations on the intermediate plate 12, it may be advantageous to arrange several working passages and working chambers on both sides of a single intermediate plate 12. In this case, the thickness T of the cassette is determined by the depth of the movable range of the largest diaphragm on each side of the intermediate plate. For example, if the depth E of the movable range of the pump diaphragm is the same on each side of the intermediate plate 12, the thickness T of the cassette will be equal to (2xE)+(3xP).

[0023] Figures 4A and 4B show an alternative embodiment of the diaphragm pump of the pump cassette 50. In this case, the fluid ports of the pump chamber are replaced by a wide opening 42 through which the diaphragm 44 can pass as it moves from the filling position (Figure 4A) to the delivery position (Figure 4B). Thus, the overall thickness T’ of this cassette is determined by adding the thickness P of the two outer plates 46, 48 to the total movable range distance or length E’ of the diaphragm 44. The pump diaphragm 44 substantially utilizes the overall thickness of the cassette 50 to substantially increase the stroke volume of the pump. In this case, the pumping chamber 52 is formed by the liquid side of the diaphragm 44 and a circumferential seal wall 54 covered by the second outer plate 48. Liquid inlet / outlet pump ports 56, 58 are shown in this embodiment, but in other embodiments, may include only a single port that functions as both an inlet and an outlet, or may include multiple ports where the function of the inlet or outlet is determined by a downstream valve in the liquid passage associated with each pump port. In this configuration, in the absence of an intermediate plate, the stroke volume generated by the diaphragm is substantially doubled, so that the overall thickness of the cassette can be minimized. Thereby, for any desired pump stroke volume, the distance between the plates can be substantially reduced.

[0024] Figures 5A and 5B show additional mechanisms that can optionally be included in a pump or valve cassette. In this case, diaphragms 60, 62 are shown to be fixed to intermediate plate 12 by a diaphragm retainer or retaining wall 68 (see also retainer 100 in FIG. 8). In other embodiments, the individual peripheral beads 64, 66 of diaphragms 60, 62 can be fixed to the intermediate plate 12 by an adhesive, by heat welding, by overmolding a section of the intermediate plate to surround and clamp the bead, by applying a solid continuous ring in a predetermined position to the diaphragm bead, or by many other ways that ensure that the diaphragm is fixed to the intermediate plate and a seal is formed between the diaphragm bead and the intermediate plate to separate the liquid chamber 28 from the working chamber 26. In the example shown, the retainer or retaining wall 68, 100 is installed inside the surrounding wall 30 of the working chamber 26. As shown in cross-section, the illustrated portion of the retaining wall 68 shows two fenestrations, slots, windows or holes 70 that allow the working pressure (e.g., air pressure) to be transmitted to the working side of the diaphragm 60. For most of its circumference, the retainer or retaining wall 68 extends without interruption from the inside of the first outer plate 14 or 46 to a position adjacent to the beads 64, 66 of the diaphragms 60, 62. When the beads are made of an elastomeric material, the retainer or retaining wall 68, 100 acts to partially compress the beads during cassette assembly when the first outer plate is attached to the opposing intermediate plate. The tight fit helps ensure that the diaphragm is securely attached and an airtight / watertight seal is formed. In a preferred configuration, the perforations 70 (or holes) of two or more retaining walls can be distributed around the retaining wall 68, such that a positive or negative working pressure can be transmitted relatively simultaneously to multiple sections of the diaphragms 60, 62.

[0025] In some cases, it may be advantageous to ensure that there is a continuous rigid clamping structure around the entire circumference of the diaphragm bead or rim. In that case, the plurality of holes in the retaining walls 68, 100 may be preferable to slots extending to the diaphragm bead. Alternatively, a continuous rigid ring (e.g., a metal washer or a plastic washer) (not shown) applied to the diaphragm bead can be combined with the slotted retaining walls 68, 100 to achieve the same result. Preferably, the outer end portion of the ring or washer abuts against the inside of the peripheral wall of the valve or pump station to compress only the bead portion of the diaphragm, and the inner end portion of the ring or washer avoids contact with the diaphragm when the washer transitions from the diaphragm bead to the diaphragm body.

[0026] In the example shown, the diameter of the retainer or retaining walls 68, 100 is small enough to allow a gap 72 to exist between the retainer or retaining walls 68, 100 and the peripheral wall 30 of the working chamber 26. The gap 72 allows the operating pressure of the fluid or air to be distributed to the individual perforations 70 of the retaining wall 68. The retainer or retaining walls 68, 100 can be separate elements assembled together with the other components of the cassette, or the retainer or retaining walls 68, 100 can be formed or co-molded with either the intermediate plate 12 or the first outer plate 14 of the cassette.

[0027] Figures 5A and 5B also show that the inner walls of the actuating or first outer plates 14 or 46 can optionally include curved buttresses 74 or 76 that assist in conforming the inner wall of the actuating chamber 26 to the curvature of the diaphragms 60, 62 when the diaphragms 60, 62 are fully expanded toward the actuating side first plate 14 or 46. This can help reduce the stress applied to the more peripheral portions of the diaphragms 60, 62 when they are fully retracted within the actuating chamber 26. Similarly, as shown in Figure 5B, a curved buttress 78 can be disposed along the end wall (liquid or second outer plate 48) of the liquid pumping chamber 52 for similar reasons. In these examples, it is not necessary to increase the overall thickness of either cassette 10 or 50 in order to form the inner walls of the outer plates 14, 46, and 48. The buttresses 74, 76, 78 can be separate inserts attached to the individual outer plates or can be formed and co-molded with the outer plates such that any additional thickness of the outer plates encroaches on the space between the plates rather than extending beyond the outer surface of the outer plates. The outer plates may be shaped to curve inwardly from the outside of the plate toward the actuating chamber or the liquid chamber while not increasing the overall thickness of the cassette.

[0028] FIG. 6 shows a rear perspective view of an exemplary cassette 80 that includes a plurality of valve stations 82 and an exemplary pump station 84. In one example, the cassette is configured to have a length of approximately 16 cm, a width of approximately 19 cm, and a thickness of approximately 1.5 cm. The first outer or actuating plate 86 is formed with recesses in its outer surface to provide a curved inner surface that conforms to the associated diaphragms within these regions at the stations of valves 82 and pump 84. In this example, the nominal thickness of each of the first outer plate 86, the second outer or liquid side plate 88, and the intermediate plate 90 is approximately 2 mm, while the overall thickness of the cassette is approximately 15 mm. The first interplate space 92 and the second interplate space 94 each have a width of approximately 4.5 mm. In this example, the pump diaphragm has a movement range approximately equal to the 4.5 mm wide first interplate space 92. The cassette actuating passage port 96 is shown arranged within the first interplate space 92 of the cassette 80. Thus, the approximately 4.5 mm diaphragm movement range can be achieved with a cassette having a width that adds the desired width for the liquid passage in the second interplate space 94 to approximately 10.5 mm. In this case, the second interplate space 94 has the same width as the first interplate space 92, although in other embodiments, the second interplate space 94 can be less (depending on the desired flow characteristics for the liquid passage). In this example, the movement range of the cassette diaphragm is approximately 30% of the overall cassette width. FIG. 7 shows a front perspective view of the cassette of FIG. 6 that reveals the cassette liquid passage port 98 arranged within the second interplate space 94 of the cassette 80.

[0029] FIG. 8 shows a perspective view of the inside of the first outer plate 86 of the cassette 80. In this example, the diaphragm holders or retaining walls 100, 102 are formed as an integral part inside the first outer plate 86 (in a dual-duty cassette, both the first and second outer plates may include holders or retaining walls 100, 102 since both sides of the intermediate plate can be the pump or valve actuation side). In this example, each diaphragm holder 100, 102 has a number of perforations or holes 104 and optionally has an upper surface groove 106 for evenly distributing the operating pressure across the entire diaphragm held against the intermediate plate 90. The curved inner wall 108 of the outer plate 86 at the valve and pump stations is arranged to conform to the diaphragm shape associated when the diaphragm fully expands within the actuating chamber (where the holder 102 is located). In some cases, optionally, ribs 109 may be included in the molding of the outer plate 86, and the ribs 109 are configured to erode the mating actuation passages of the opposing intermediate plate. The ribs 109 may be configured to have a cross-sectional size and length to adjust the total volume of the associated actuation passage to a predetermined volume (this helps to minimize the amount of pneumatic gas volume supplied (or compressed) and may improve the responsiveness of the associated diaphragm to actuation by the pressure supply manifold).

[0030] The actuation volume adjustment ribs can be particularly advantageous in configurations where both sides of the intermediate plate are equipped with actuation passages and / or fluid passages, or where the plate-to-plate space has to accommodate a wider diaphragm movement range. In that case, by attaching the actuation volume adjustment ribs, the transmission volume of the actuation passage can be reduced and the performance of the cassette can be improved. Further, when synchronous valve actuation is desired, it can be advantageous to match the actuation passage transmission volumes between multiple sets of valves where the distance from the actuation ports of the cassette varies. Thus, the operation of the cassette valves can be finely tuned using appropriately sized volume adjustment ribs.

[0031] FIG. 9 shows a perspective view of the working side of the intermediate plate 90 of the cassette 80. In this example, the working passage 110, the peripheral wall 112 of the valve and the pump station, and the cassette working port 96 are formed or molded as part of the intermediate plate 90. In this example, most of the diaphragm valve or the pump station is supplied by a separate working passage 110 that continues from the dedicated cassette working port 96. The fluid passage or the working passage of the cassette can be an individually formed conduit, or each passage can be fused to either the intermediate plate and the first outer plate or the second outer plate, and include two walls spanning the space between the plates that extend therebetween. In some cases, it is desirable to operate two or more valve stations at once, in which case, as shown in valve stations 116, 118, a single working passage path 114 can supply two or more valve stations. Each valve station is surrounded by a peripheral wall 112 that seals the station when the adjacent first outer plate 86 is welded to the intermediate plate 90.

[0032] The cassette plates can be formed (e.g., injection molded) from a moldable plastic material such as polysulfone that hardens to a hard or hard consistency. Other materials such as other plastics or metals can also be used. In addition to other molding methods, new technologies such as 3D printing can be used to form the intermediate plate and the outer plates. The outer plates can be joined to the intermediate plate using an adhesive or local heating by ultrasonic or mechanical vibrations. In a preferred method, the outer plates can be made transparent, translucent, or can allow transmission of laser wavelengths to enable laser welding of the outer plates to the opaque intermediate plate. The welding seals the valve and pump regions of the outer plates to the peripheral walls and passages of the individual valve and pump stations of the intermediate plate.

[0033] Each surrounding wall 112 forms part of the working chamber of an individual valve or pump station, and each surrounding wall 112 communicates with the working passage 110 via a working chamber port 120 within the surrounding wall 112. The pump station 84 in this example has two pump ports 24a, 24b that connect liquid passages on the opposite side (the second side) of the intermediate plate to the first side of the intermediate plate shown in the figure. One of these functions as the inlet of the pump chamber and the other functions as the outlet of the pump chamber. In other embodiments, the pump region can have a single pump port or multiple pump ports. The multiple valve stations in this example each have two ports that connect two separate liquid passages on the second side of the intermediate plate to the valve station on the first side of the intermediate plate shown in the figure. Also, in this example, one of the valve ports 34a has a raised peripheral lip 40 to improve the seal of the valve diaphragm against the valve port when positive pressure is applied to the diaphragm.

[0034] Figure 10 shows an enlarged view of the intermediate plate 90 of Figure 9. In this case, the pump diaphragm 122 and the valve diaphragm 124 are shown to be installed at individual pump stations and valve stations. The diaphragms are held in place and sealed against the intermediate plate 90 by the corresponding retaining walls or holders 100, 102 shown in Figure 8. Note that the retaining walls or holders 100, 102 fit (loosely) within the circumference of the surrounding wall or chamber wall 112 of the individual valve or pump station. The difference in diameter between the surrounding wall and the retaining wall is sufficient to allow a gap 72 (see Figure 5A) to exist between the two so that the working fluid or gas pressure can be evenly distributed around the associated diaphragm.

[0035] FIG. 11 shows a second side of the intermediate plate 90 of the cassette 80. In this example, the liquid passage 126 is formed as part of the intermediate plate 90. In the case of the pump station 84, each of the two ports 24a, 24b is associated with a separate liquid passage 128, 130, such that one port functions as an inlet port of the pump chamber and the other port functions as an outlet port of the pump chamber. Whether a particular port functions as an inlet or an outlet can be determined by which downstream valve is actuated or closed.

[0036] FIG. 12 shows a variant of the cassette 132 that includes an additional optional mechanism (which may be individually included or excluded in any cassette design). In this case, the cassette incorporates actuation ports, actuation passages, and actuation chambers on both sides of an intermediate plate 134. Each of the first interplate space 136 and the second interplate space 138 includes both actuation passages and liquid passages, as well as actuation ports and liquid cassette ports. In this figure, two rows of actuation ports 140, 142 can be seen at the ends or narrow side faces of the cassette, thereby enabling the ends of the cassette to be inserted into a connector or interface that communicates with a pressure distribution manifold. In this embodiment, the overall thickness T2 of the cassette, which is the sum of the thicknesses of each of the intermediate plate 134, the first outer plate 144, and the second outer plate 146 plus the widths of the first interplate space 136 and the second interplate space 138, allows a pump diaphragm or valve diaphragm to be placed on the first or second side of the intermediate plate, or on both. This potentially increases the number of valve or pump stations that can be installed in a cassette having a particular wide side dimension. In this embodiment, the overall thickness T2 of the cassette can be minimized while maximizing the density of pump or valve stations that can be included in the cassette 132, and the movable range of the contained diaphragm constitutes a substantial majority of the overall thickness of the cassette. For example, in a cassette with such a "double-duty" intermediate plate (which allows actuation passages and chambers on both sides of the intermediate plate), the nominal plate thickness is 2 mm, combined with 5 mm interplate spaces on each side, resulting in an overall cassette thickness of 16 mm to accommodate a 5 mm movable range of the diaphragm, with approximately 2 / 3 of that constituting the desired diaphragm movable range.

[0037] Figures 12 and 13 show an intermediate plate 150 of a dual duty cassette that includes both an actuation passage and a liquid processing passage in which each of a first side surface 152 and a second side surface 154 of the intermediate plate incorporates actuation ports, actuation passages, actuation chambers, and liquid passages on each side of the intermediate plate. A plurality of valve stations 156 are shown in this example, although on-board pump stations can also be included in other embodiments. In this regard, the cassette is similar to cassette 132 of FIG. 12.

[0038] Optionally, this intermediate plate 150 is additionally designed to be used in a cassette assembly incorporating an outboard pump pod or a liquid mixing pod, but this is because the volume requirements of the outboard pump pod or the liquid mixing pod prevent them from being included as on-board pump stations or mixing chamber stations on individual cassettes. When a larger stroke volume is required, two or more cassettes can be arranged so that the liquid lines or actuation lines are connected to extension conduits 158, 160 perpendicular to the face of the cassette and connectable to an external pod located between the two cassettes. The conduits (e.g., formed or molded with the intermediate plate) originate from the cassette intermediate plate, pass through either the first or the second outer plate, and provide a direct connection to an external self-contained diaphragm pump, a self-contained mixing chamber, or a self-contained balancing chamber. When the conduits are rigid, they can also function as structural members to assist in holding the cassette assemblies together. The vertical conduits may be used as liquid ports for connecting to a fluid source or a fluid destination outside the cassette. In this case, the ends of the conduits can be configured to make a connection with a flexible or malleable tube. In this type of cassette, the cassette actuation ports and the first part of the actuation passageways can all remain arranged within the space between the plates of the cassette until the fluid lines or actuation lines reach the point where they must connect to the associated pod pump, balancing chamber pod, or mixing chamber outside the cassette. In this configuration, since the cassette actuation ports are more efficiently arranged, the cassette assembly is substantially improved over previously disclosed cassette assemblies. Since all the actuation ports are arranged along the ends of the cassette, the cassette can be directly inserted into the associated pressure supply manifold or rigid receptacle array without the need for flexible tube connections or individual connectors.

[0039] The cassette intermediate plate 150 of FIGS. 12 and 13 also shows that the actuation passages and the liquid passages can be routed from the first side surface of the intermediate plate to the opposite second side surface in order to increase the number of valve stations or pump stations that can be incorporated within a cassette of a particular size. Routing of the actuation passages or the liquid passages can be difficult due to the presence of other passages, pump stations, or valve stations that obstruct a direct route from the cassette port to the desired valve station or pump station. In that case, redirecting the actuation passages or the liquid passages to the first side surface / second side surface of the intermediate plate can enable the passages to bypass an obstructing structure on the second side surface / first side surface of the intermediate plate. The bypass passage may simply make a penetration to the opposite side surface of a single intermediate plate, or may penetrate through the intermediate plate to bypass the obstructing structure and then return to the starting side surface of the intermediate plate to reach the desired pump station or valve station. FIG. 14 shows the second side surface 154 of the cassette intermediate plate 150. The actuation port 162 configured to supply the valve station 164 lacks an unbroken path to the valve station due to the presence of the extension conduit 168. The actuation passage 170a connected to the cassette actuation port 162 terminates at an actuation passage port 172 that penetrates the intermediate plate 150. As shown in FIG. 13, the actuation passage 170b on the first side surface 152 of the intermediate plate 150 connects the actuation passage 170a to the actuation passage 170c via the actuation passage port 174 to complete the path of the actuation passage from the cassette actuation port 162 to the valve station 164.

[0040] Regardless of whether the cassette includes actuation passages and chambers, and fluid passages, on both sides of an intermediate plate (i.e., a dual-duty intermediate plate), the cassette can be arranged to have a fluid cassette port disposed at the narrow side or end of the cassette, such that a plurality or bank of such cassettes can be stacked together to form a compact cassette group. FIG. 15 is a rear perspective view of a cassette group 176 consisting of a plurality of individual cassettes 178a-d stacked from wide side to wide side. Each of the cassettes 178a-d has one or more cassette actuation ports 180 disposed on the narrow side of the cassette within the first plate space 182a-d, the actuation ports being oriented in the same direction such that the individual cassettes of the cassette group can be inserted into corresponding connector ports or receptacle ports of the individual receptacle assemblies, the connector ports or receptacle ports being disposed adjacent to each other and connected, mounted, or attached to a pressure distribution manifold.

[0041] The cassettes of the cassette group can be arranged to contact each other regardless of whether they are joined or adhered to each other. Alternatively, they can be provided with play or arranged adjacent to each other with a certain spacing so that each cassette of the group can be individually inserted into or removed from its corresponding receptacle assembly without interfering with adjacent cassettes. Thereby, the individual cassettes can be placed on rails or tracks to properly align the operating ports with individual connectors or receptacles, enabling easier insertion and removal. The cassette receptacle assemblies can be arranged adjacent to each other to provide a spatially compact cassette group. Optionally, the cassette receptacle assemblies can be arranged within a single housing, thereby providing alignment and insertion / removal tracks for individual cassettes. Or each cassette receptacle assembly may be included in a separate housing for the same purpose. In a configuration that provides individual fluid circulation to the array of objects, this configuration allows a single cassette to be exchanged with cassettes having different mechanisms (with respect to the number and distribution of pump stations and valve stations, and the liquid flow path). Thus, when the fluid circulation requirements for individual objects change, the configuration of the cassette group allows the cassettes to be conveniently and quickly adapted according to the needs of the associated objects. Further, adjacent cassettes of the cassette group can be interconnected via their individual liquid ports, for example, by jumper lines. In this way, when it is necessary to provide a solution containing a specific component at a specific concentration to an object, complex liquid mixing procedures can be performed. Thus, one or more cassettes of the cassette group can be dedicated to a single object as needed.

[0042] FIG. 16 is a front perspective view of the cassette group 176 of FIG. 15. In this example, for the sake of illustration, the cassette liquid ports 184 are disposed on the narrow side surfaces of each of the cassettes 178a - d on the side opposite the actuating port 180. The actuating ports are preferably disposed at the same corresponding ends of the cassettes (so that the pressure delivery manifold can be disposed behind the cassette group), but the liquid ports of the individual cassettes need not all be disposed along the same end of the cassettes. In this embodiment, the cassette liquid ports 184 are disposed within the second plate - to - plate spaces 186a - d of the individual cassettes 178a - d. Thus, the cassette group 176 can be oriented to face outward from one or more receptacle assemblies (not shown) that are connected to, mounted on, or attached to the pressure distribution manifold. Since each of the cassettes 178a - d can provide liquid circulation to an individual target, the number of individual cassettes within the group can be matched to the number of targets requiring liquid circulation. For example, circulating liquid, drugs, nutrients, or other chemicals can be supplied to a plurality of biological cell stations, tissues, or organs arranged for growth, experimentation, or testing by the plurality of cassettes within the cassette group, and each cassette can potentially supply a liquid solution having a similar or different composition to each cell station, tissue station, or organ station. A cassette group such as the cassette group 176 can also be configured to function as a solution mixing station, where the liquid output of one cassette in the group provides the liquid input to an adjacent cassette in the group, enabling complex solution mixing protocols. Thus, two or more cassettes can be reconfigured to supply a single target.

[0043] FIG. 17A of cassette group 186 incorporating dual-duty intermediate plate cassettes 188a - d shows a rear perspective view, and FIG. 17B shows a front perspective view. In other embodiments, the cassette group can incorporate one, two, or more than two dual-duty intermediate plate cassettes within one or more single-duty intermediate plate cassettes. In this example, the actuating ports 190 of representative second plate spaces 182a - d and the liquid ports 192 of representative first plate spaces 186a - d are shown. Depending on the number and size of the individual pump stations and valve stations within cassettes 188a - d, using dual-duty intermediate plate cassettes can enable placement of a higher density of multi-purpose valve stations and pump stations within a relatively limited space.

[0044] In some applications, the stroke volume of a pump or other type of chamber, or the volume of a liquid chamber, exceeds the volume that can be accommodated by an on-board pump or chamber. In this case, an outboard pump or chamber pod is used and is disposed between two cassettes. Liquid lines and / or actuation lines originate from opposing faces of the two cassettes to supply the outboard pump or chamber, enabling the liquid to flow, for example, from a first cassette to the outboard pod and subsequently to a second cassette, and each cassette houses an upstream or downstream valve station for controlling the liquid flow. Alternatively, the outboard pump actuation line can originate from a face of the first cassette, and the liquid inlet and outlet lines can originate from the opposing second cassette. This type of cassette assembly was also capable of directly connecting the liquid lines from a face of one cassette to the face of the opposing cassette. In a conventional embodiment, as shown in FIG. 18, the opposing faces of cassettes 194, 196, 198 included a liquid port 204, liquid lines 206 and actuation lines 208 to an outboard pump 210 or chamber 212, an actuation port 200 for an on-board pump station, and an actuation port 202 for a valve station. With this configuration, a number of flexible tube connections for both the liquid lines and the actuation lines were inserted into the inner face of the cassette, presenting challenges with respect to manufacturing, assembly, and maintenance.

[0045] FIG. 19 shows a conventional cassette assembly in which a pneumatic actuation line 214 extends from an actuation port 216 on a cassette face 218 to block connectors 220a, b for subsequent connection to a pressure distribution manifold used to operate the cassette assembly. This was in addition to liquid lines 222 extending from liquid ports 224 on individual cassettes. This type of cassette assembly was substantially improved by incorporating the cassette design of the present disclosure.

[0046] Dialysis Cassette Assembly FIG. 20 is FIG. 17A, 17BAn example of a cassette assembly 226 that performs a liquid handling function substantially similar to that of the conventional cassette assemblies of 18 is shown to help explain how the cassettes of the present disclosure can substantially improve the structure, assembly, and maintenance of such cassette assemblies. In this example, the illustrated cassette assembly 226 is used to mix, process, and move dialysis fluid within a portable hemodialysis device. However, the use of this type of cassette or cassette assembly (i.e., a cassette having end-mounted actuating ports with actuating passages extending between plates and parallel to the cassette face) is not limited to hemodialysis systems. As shown in FIG. 20, three cassettes 228, 230, 232 are coupled together by fluid handling pods 234, 236. These inter-cassette pods can include a self-contained diaphragm pump having both actuating and fluid conduits, or other liquid conveyance chambers 236 having only fluid conduits. Examples of other types of liquid conveyance pods include fluid mixing chambers or fluid balance pods where the flow through a first fluid line is balanced by the flow through a second fluid line via a pod having a first variable volume separated from a second variable volume by a flexible diaphragm. Each fluid handling pod 234, 236 is fluidly connected, either by a flexible or a rigid conduit, to either or both of the adjacent cassettes. A rigid liquid conduit 238 can be preferred as it can provide structural support for the cassette assembly. In the case of the diaphragm pump pod 234, both the liquid conveyance conduit and the actuating conduit can extend to one or both of the adjacent cassettes. The conduit 238 penetrates the face of the adjacent cassette to reach a fluid or actuating passage located within the first or second plate space of that cassette. Generally, the actuating passage driving the inter-cassette pump pod proceeds without interruption from the cassette actuating port to the actuating chamber of the pump pod. The fluid passage of either the inter-cassette pump pod or another type of fluid handling pod connects to the corresponding inter-plate fluid passage of one or both of the adjacent cassettes via one or more diaphragm valves disposed within the cassette.The actuation passages of these diaphragm valves, the actuation passages of the pump pods, and any other actuation passages within the cassette pass through the space between the first or second plates of each cassette to reach the first end of the individual cassette and terminate at the actuation port 240 of the cassette. In the cassette assembly, each cassette 228, 230, 232 has an actuation port 240 disposed on the narrow side surface or end of the individual cassette, and is configured to face in the same direction such that the actuation ports of the cassette assembly occupy one side surface of the cassette assembly. This allows the cassette assembly 226 to be inserted into or removed from one or more receptacle assemblies in a single operation. This configuration eliminates the need for flexible tubing to connect the cassette actuation ports to the corresponding manifold output ports. In the example illustrated in FIG. 20, the cassette 228 is optionally configured as a single-duty intermediate plate cassette (all actuation ports are disposed in either the first plate space or the second plate space). In the same example, the cassettes 230 and 232 are optionally configured as dual-duty intermediate plate cassettes, and some actuation ports are disposed in both plate spaces on both sides of the cassette intermediate plates 242, 244. Other arrangements are of course possible depending on the fluid processing tasks required of the similarly configured cassette assembly.

[0047] FIG. 21 shows an exploded view of an exemplary cassette assembly 226 illustrated in FIG. 20. The assembled cassettes 228, 230, and 232 are held within the frame assembly along with the inserted pump 234 or other liquid conveyance chamber 236, ensuring proper alignment of the cassette ports during installation and operation. Conventionally disclosed cassette assemblies could rely on rigid conduits (e.g., conduit 238) and several retaining bars or springs for holding the assemblies together (see FIG. 18), but did not require precisely aligned working ports for direct insertion into the manifold assembly. In the cassette assembly disclosed herein, the carrier frames 505 and / or 507 can address this concern by compactly securing the cassette assembly 226 and holding the cassette assembly 226 in the required configuration or alignment. The exemplary embodiments of FIGS. 20 and 21 show a first carrier frame 505 and a second carrier frame 507 that can engage the cassette assembly 226 from opposing directions. Some embodiments can provide similar carrier frames for securing the cassette assembly 226 from adjacent sides. Other embodiments can also provide a monolithic carrier frame for securing the cassette from two or more opposing sides.

[0048] Carrier frames 505 and 507 can further include plate rails that can slide across the corresponding cassette plates of cassettes 228, 230, and 232 to engage with cassette assembly 226. By connecting the frame components to each other and fixing the enclosed cassette plates to the rails, there is no need to pierce or drill holes in any of the three cassette plates to fix them to the frame. The rail configuration and the absence of screws, nuts, or clips passing through the cassette plates can reduce the possibility of damaging the cassette assembly and interfering with any pneumatic connections or paths therein. 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 be provided with elongated slots that can partially or fully receive at least one end or a part of an end of the corresponding cassette plates of cassettes 228, 230, and 232. For example, referring to the first carrier frame 505, the plate rails 505A, 505B, and 505C can receive the ends of the cassette plates of cassettes 228, 230, and 232, respectively. In one embodiment, the rails can include capping features. For example, the rails 505A and 505C of the first frame 505 can include capping mechanisms 505F and 505G disposed at the ends of the individual rails. The plate rails 507A, 507B, and 507C can engage with the cassette assembly 226 by receiving the ends of the corresponding cassettes 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 cradle the corresponding rigid liquid conduits 238 when the carrier frames 505, 507 engage with the cassette assembly 226.The plate rails 505A, 505C, 507A, and 507D can have closed ends and open ends. The open ends of the rails may be included to avoid interference with the nearby cassette ports 240. Note that the first and second carrier frames 505 and 507 can slide over the respective cassette ends and engage the cassette assembly 226 and may not require additional fixing means for directly engaging the cassettes 228, 230, and 232. Further, fixing mechanisms that complement the rails, such as, but not limited to, capping mechanisms 505F, 505G, and notches 506 and 508, can further strengthen the engagement between the cassette assembly and the frame, and thus can more uniformly disperse any force applied to the frame onto the cassette assembly, potentially avoiding distortion or deformation of the cassette assembly 226. This configuration can serve to compactly attach and remove the cassette assembly 226 from the array of manifold receptacles of the hemodialysis device 246 without creating difficulties for the cassette assembly that would lead to misalignment of the cassette ports.

[0049] The plate rails 505A, 505B, and 505C can be interconnected by upper bars 505D and lower bars 505E that extend perpendicular to the plate rails. The lower bar 505E interconnects the plate rails 505A - 505B and 505B - 505C in the vicinity of the open ends of the rails and the cassette ports 240. The upper bar 505D interconnects the plate rails 505A - 505B and 505B - 505C at the closed ends of the rails. Similarly, the rails 507A, 507B, and 507C are interconnected by upper bars 507D and lower bars 507E that extend perpendicular to the plate rails. The lower bar 507E interconnects the plate rails 507A - 507B and 507B - 507C in the vicinity of the open ends of the rails and the cassette ports 240. The upper bar 507D interconnects the plate rails 507A - 507B and 507B - 507C at the closed ends of the rails.

[0050] When the frame is arranged to engage with the cassette assembly 226, at least one crossbar 511 can be arranged to connect the first and second carrier frames 505, 507. In this example, the crossbar 511 is arranged to pass longitudinally through the cassette assembly 226 and connects the first and second carrier frames 505, 507 at both ends of the crossbar. This configuration helps to stabilize the sides of the frames 505, 507 in the vicinity of the ports 240 of the cassettes 228, 230, 232. The crossbar 511 helps to prevent the frames 505, 507 from shifting in position relative to the cassette assembly 226. The connection between the individual ends of the crossbar 511 and the corresponding carrier frames 505, 507 can be established by fastening mechanisms such as screws, bolts, adhesives, laser or ultrasonic welding, or other similar fastening mechanisms not limited to these. Optionally, the cassette assembly 226 can provide alternative or additional connection elements between the first carrier frame 505 and the second carrier frame 507 for fixing them to each other, and the cassette assembly 226 can include, but is not limited to, clips similar to the clip 512 of FIG. 18, threaded rods, or zip ties, or other elements that limit the degree to which the frames 505, 507 can shift relative to each other.

[0051] Figures 20 and 21 further illustrate the first support plate 513 and the second support plate 515. The first support plate 513 can be arranged to interconnect the first and second carrier frames 505, 507 that engage with the cassette assembly 226. In this example, the first support plate 513 is arranged on a side surface of the cassette assembly 226 that is perpendicular to the side surface on which the first and second carrier frames 505, 507 are arranged. Further, the first support plate 513 is arranged on the carrier frame on the side opposite to the cassette port 240. The first support plate 513 can further include flanges 513A and 513B at both ends. These flanges 513A, 513B can be configured to engage with the upper bars 505D, 507D of the first carrier frame 505 and the second carrier frame 507. The first support plate 513 can be mechanically fixed to the upper bars 505D, 507D with clips, screws, or the support plate 513 can be coupled 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 with the upper bars 505D, 507D when the carrier frame engages with the ends of the cassettes 228, 230, 232 of the cassette assembly 226. Thus, the first support plate 513 and the crossbar 511 can fix the first and second carrier frames 505, 507 to each other during engagement with the cassette assembly 226. The assembly including the carrier frames 505, 507, the crossbar 511, and the first support plate securely holds the cassette assembly 226 and helps to evenly distribute external mechanical forces over the components of the cassette assembly to prevent their relative positions from being distorted.

[0052] The first support plate 513 can further provide an inner surface 513D (see FIGS. 22A and 22B) facing the cassette assembly 226 and an outer surface 513C facing away from the cassette assembly 226. During installation of the cassette assembly 226, the outer surface 513C of the first support plate 513 can interact with a cassette loading device (not shown) described below. The inner surface 513D and the outer surface 513C provide surfaces on which the cassette loading device can apply a force to move the cassette assembly as a unit. The first support plate 513 can also provide an alignment mechanism for properly loading and positioning the cassette assembly 226 in the loading device.

[0053] FIG. 21 also shows a second support plate 515 that can optionally be included to engage with one of the carrier frames 505, 507 to minimize twisting or bending of the frame. In this example, the second support plate 515 is attached to the second carrier frame 507 and to the frame via a connection element 519. The connection can be achieved by seating the connection element 519 in a corresponding connection junction 520 provided on the second carrier frame 507. In another embodiment, the second carrier frame 507 can be integrated with a support plate, such as the second support plate 515, as a single component, among other things. The deflection or twist of the first carrier frame 505 can also be reduced by including a diagonal cross member 523. The cross member 523 can be integral with the structure of the second carrier frame 505 or can be attached separately to the frame. Additional support elements similar to the support plates 513, 515 and the support bracket 523 can be provided to complement the carrier frames 505, 507 and maintain the required placement of the cassette assembly 226.

[0054] Figures 22A and 22B show perspective views of an exemplary first support plate 513. Flanges 513A and 513B can further provide an engagement mechanism such as, but not limited to, elastic clips or grippers 514. The first support plate 513 can also include one or more clips 514 on the side without a flange. The clips 514 can be configured to engage the ends 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 nubs 516 (FIG. 21) can be included at the ends of the carrier frames 505, 507. The nubs 516 can serve as an alignment mechanism 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 this embodiment, the first support plate 513 can include longitudinal and / or transverse reinforcements 517 to reduce mechanically induced deformation of the first support plate 513.

[0055] FIG. 23 shows a hemodialysis device 246 configured to surround a cassette assembly 226. The front panel 248 is configured to include a recess and holder 250 for the dialyzer and a blood pump cassette receptacle assembly 252, and is configured to hold a blood tubing set (not shown). The dialysate cassette assembly 226 is configured to be housed within an enclosure of the device 246 behind the front panel 248.

[0056] FIG. 24 shows the enclosure 254 of the apparatus 246 of FIG. 23, with the front panel 248 and other components removed. The internal configuration of the enclosure or housing 254 allows the cassette assembly 226 to be placed on the internal shelf 256 of the enclosure 254. The interior of the enclosure 254 (e.g., below the shelf 256) is configured to hold other components such as a heater for the dialysate solution, tubes for various liquid flow paths, a dialysate reservoir or tank, and one or more devices for detecting the conductivity and temperature of the dialysate solution at various stages of mixing. Behind this enclosure 254, there is a recess 258 configured to hold a pressure distribution manifold with electromechanical valves (in this case, a pneumatically actuated manifold) and one or more electronic controllers configured to control at least one of the electromechanical valves of the manifold. These components are arranged outside the enclosure 254 to assist in protecting them from the high temperatures that can be used when sterilizing the liquid transport components of the hemodialysis apparatus 246. FIG. 25 shows a rear perspective view of the enclosure 254, highlighting the recess 258 located directly below the shelf 256 of the enclosure 254. Thus, the pressure distribution manifold can be placed directly below the cassette assembly 226, the cassette assembly is arranged within the enclosure 254, and the pressure distribution manifold is arranged outside the enclosure 254.

[0057] Loading and locking of cassette assembly Figures 30 and 31 show the installation and retention of cassette assembly 226 within enclosure 254. In Figure 30, cassette assembly 226 is lifted directly above three cassette receptacle assemblies, and the three arrays of cassette activation ports 240 are aligned with the respective receptacle ports on adapters 266, 268, 270. The receptacle assemblies are configured to mate the activation port array of cassette assembly 226 with the activation outlets of a pressure distribution manifold disposed below shelf 256 and outside of the enclosure. By lowering cassette assembly 226, cassette activation ports 240 can be engaged with the respective adapters via press-fit connections. Sealing of the individual activation ports 240 can be accomplished by using an O-ring, or a gasket with elastomeric wiper seals, or other means commonly used when sealing press-fit connections. Next, the adapters can provide a direct connection to the output ports of a pressure distribution manifold (Figures 32 - 37) located below shelf 256 and outside of enclosure 254. Figure 30 further shows a cassette loading device 292 that can receive cassette assembly 226 during installation and hold it in place. A handle 308 belonging to loading device 292 can be operated to lock the cassette assembly within enclosure 254. A detailed description of the operation of device 292 and handle 308 for locking and holding the cassette assembly is provided below with reference to Figures 56 - 59. In one configuration, the loading assembly of Figure 30 can be in an open position showing an operating handle extending parallel and away from the cassette assembly. Figure 31 shows that operating handle 308 is tilted downward, indicating that the loading device has been moved toward the receptacle assembly of the manifold, thereby pushing and fixing cassette assembly 226 into the corresponding adapter ports, showing that cassette assembly 226 has been locked within the cassette receiving space.In this example, the loading device 292 can include, but is not limited to, force application elements such as one or more bars that can interact with a first support plate 513 (Figs. 22A and 22B) and can be operated by a handle 308. By lowering the handle 308, it can be made possible for the force application element to press on the first support plate 513. This force can be transmitted to the cassette assembly 226 via the cassette frames 505, 507, and the frames press the cassette assembly 226 toward the adapters 266, 268, and 270. FIG. 31 shows the cassette assembly 226 in an operable configuration. That is, the cassette assembly 226 is pressed such that the array of cassette operation ports 240 is aligned with their respective adapters 266, 268, and 270. Note that the handle 308 in FIG. 31 is shown in a closed state. That is, the cassette assembly 226 is locked inside the enclosure 254, and the handle is arranged such that it can be installed without interfering with the front panel of the hemodialysis device.

[0058] The hemodialysis device 246 of the embodiment shown in FIGS. 45 and 46 includes an enclosure 254 in which the footprint of the cassette assembly 226 extends in the forward direction of the shelf 256 and projects from the shelf 256. For this reason, as shown in FIG. 45, a group of manifold interfaces or adapters 266, 268, 270 are configured to extend in the forward direction of the shelf 256. The adapters 266, 268, and 270 provide the necessary mating between the operating ports 240 of the cassette assembly 226 and the individual connectors or receptacle ports 272 disposed on the interfaces or adapters 266, 268, 270. The adapters 266, 268, 270 in this example function as receptacle assemblies and provide an array of receptacle ports for mating with the cassette ports 240 respectively arranged in each of the cassettes 228, 230, and 232. FIG. 46 shows a bottom perspective view of the enclosure 254 to which the interfaces / adapters 266, 268, 270 are attached. In this figure, it is clear to what extent the adapters project from the enclosure shelf 256 (and thus also from the pressure supply manifold 260). The adapters 266, 268, 270 map the cassette ports arranged in the longitudinal direction along the ends of the individual cassettes to a more spatially compact array of manifold ports arranged in risers or upper blocks 276A - C of the upper block 274 of the pressure distribution manifold 272 thereunder.

[0059] Pressure distribution manifold FIG. 26 shows a schematic diagram of a pressure distribution manifold (or manifold assembly) of one embodiment. This manifold assembly is configured to selectively provide pneumatic pressure (positive pressure, negative pressure, or atmospheric pressure) to control pneumatic pumps and / or valves on two separate pump cassettes. In this improved embodiment, the first set of pneumatic outlets is configured for direct connection (i.e., a direct plug-in connection to the first pump cassette or cassette assembly, i.e., to the manifold assembly or to an adapter directly connected to the manifold assembly). In one embodiment, the direct connection interface is schematically shown as one or more risers or "upper blocks" 276A, 276B disposed on the upper side of the manifold assembly 260. The upper block includes a direct connection port 261 configured to connect directly to a first pump cassette (not shown) that can be disposed directly above the manifold assembly 260. The manifold or manifold assembly also includes a second set of pneumatic outlets configured to indirectly connect to a second pump cassette via a flexible or malleable tube. FIG. 26 also shows an exemplary fitting 582 for indirect connection to a second pump cassette (not shown), and the connection is configured for a flexible or malleable tube that travels a distance to a second pump cassette disposed away from the manifold assembly 260. In the context of the hemodialysis device described herein, the dialysate cassette assembly can be configured to plug directly into the manifold assembly via port 261, and the blood pump cassette assembly (disposed further away from 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 (represented here by exemplary fitting 582).

[0060] FIG. 26 shows another improvement in a manifold assembly 260 that helps prevent or reduce the accumulation of particulate or liquid debris on the internal seal surfaces of an electromechanical pneumatic control valve. The exemplary valve 267 is shown generally in a horizontal orientation. The internal valve seat or seal surface is oriented so as not to have a horizontal surface where debris can accumulate. In the schematic views of FIGS. 26-29, the lower or bottom manifold block 272 mates with the intermediate manifold block 274. The lower manifold block 272 has a cross-sectional “T” shape that includes a horizontal portion 272A and a pendant portion 272B (across the long axis “Z” of the manifold assembly 260), and a plurality of valve mounting surfaces and openings are disposed on the pendant portion 272B. The exemplary valve 267 is shown mounted on one such surface and over one such opening. A valve face seal (not shown) is envisioned to couple the valve body to the mounting surface of the pendant portion of the manifold. The pendant portion 272B is shown for convenience as having a direction perpendicular to the horizontal portion 272A. The pendant portion 272B can have a non-vertical orientation such that the valve mounting surfaces and openings are inclined upwardly such that the valve body and face seal are oriented in a downward angular direction. This angled orientation also helps prevent the accumulation of liquid (e.g., liquid condensate) or debris on valve components having a seal surface (e.g., a valve seat). In many (but not all) valve embodiments, the associated internal valve plunger or piston operates in a horizontal or nearly horizontal direction, which is represented by the valve 267 schematically shown in FIGS. 26-29.

[0061] In the example illustrated in FIGS. 26 to 29, it is shown that the pressure source line 263 is embedded within the lower or bottom manifold block 272. Depending on the piping method of the internal pneumatic passages within the manifold assembly 260, these pressure source lines can also be arranged within the intermediate block 274. In the schematic diagram shown, each of the plurality of valves 267 receives an input line from one of the pressure source lines 263 and has an output line that is ultimately connected to an output port (either the direct connection port 261 or the indirect connection port 582) of the manifold assembly.

[0062] FIG. 27 shows a schematic view of an embodiment of the manifold assembly 260 in which the direct connection blocks 276A, 276B project, are cantilevered, or are offset with respect to the body of the manifold assembly. In this figure, the major axis ("Z") of the manifold assembly can be made to conform to a pump cassette of any length in the major axis direction. However, if the pump cassette is configured to have an array of inlet ports that exceed the dimension from the front to the back ("X") of the main face of the manifold assembly, the direct connection blocks can be arranged to project in that direction from the manifold assembly. Next, the port 261 is connected to the passages within the blocks 276A, B so as to be routed to a more compact array of ports that are mapped one-to-one to the ports at the upper part of the intermediate block 274.

[0063] FIG. 28 shows a schematic view of a manifold assembly 260 in one embodiment where an array of pressure sensor ports 567 is disposed between direct connection blocks 276A and 276B. In this case, the various pneumatic passages within the manifold assembly can have branches or in-line connections to the sensor ports 567A of the pressure sensor array 567. In most cases (but not necessarily all), these passages connect to the output lines of pneumatic control valves and the output ports of the manifold assembly to which the valve output lines are connected. In one example, the array of pressure sensing ports can be configured to mate with a printed circuit board (PCB) disposed above the array and including an array of corresponding pressure sensors. The pressure sensors of the PCB can be connected to a hemodialysis controller. The hemodialysis controller uses the pressure information to control the pneumatic control valves to supply a predetermined level and pattern of pressure to a pump or valve target within the connected pump cassette.

[0064] Figure 29 shows a schematic view of a manifold assembly 260 in one embodiment that includes one or more manifold adapters or interface blocks 266, 268. In this example, the upper blocks 276A, 276B function as risers that provide a spacing between the directly connected pump cassette to be attached and the body of the manifold assembly 260. The risers may include pneumatic passages that connect a plurality of valves (such as valve 267) on the manifold to the manifold adapter or interface blocks 266, 268 and ultimately to the associated pump cassette. The manifold adapter or interface block can be configured to spatially redistribute an output port 261a disposed at a relatively narrow spacing within a riser block or other block of the manifold to an array of output ports 261b disposed at different spacings or different distributions. In this way, the directly connected output ports of the manifold assembly can be spatially arranged or redistributed to coincide with the corresponding input ports of the corresponding directly connected pump cassette. Accordingly, the manifold adapters 266, 268 include transfer ports on a first side that fit against the manifold 274 or associated risers 276A, B, and these transfer ports are mapped to corresponding transfer ports 261b on a second, opposite side that fits against the pump cassette assembly. Accordingly, a first array of manifold output ports having a first spatial port configuration can be directly mated to a second array of cassette input ports having a second spatial port configuration. The mapping between corresponding transfer ports is achieved through the routing of internal passages within the manifold adapters 266, 268. In this case, the spatial array of output ports of the manifold or riser has a shorter length than the spatial array of transfer ports of the manifold adapter on the second side of the adapter. As a result, the manifold adapter projects in a cantilevered manner from the front of the manifold. These mechanisms serve to decouple the spatial and dimensional constraints of the pump cassette assembly from the spatial and dimensional constraints of the manifold assembly configured to drive the cassette(s) of the pump cassette assembly.In an embodiment of the present specification, the manifold assembly can be made as compact as allowed by valve constraints, passage constraints, and port constraints while retaining the function of interfacing with a pump cassette that may have substantially different spatial constraints or spatial array requirements for its operating ports.

[0065] Figures 32 and 33 show details of a pneumatically actuated manifold in the form of a pressure distribution module 260. The pressure distribution module 260 provides selectable pneumatic connections from a plurality of pressure sources to receiving ports on the platforms of manifold adapters 266, 268, 270 for a cassette assembly inserted therein. The pressure distribution module 260 can further provide selectable pneumatic connections to a remote cassette via flexible or malleable pneumatic lines (not shown). The pneumatic connections are selectively controlled by digital or binary pneumatic valves 262, 265, 267 mounted within or on the manifold block. One or more controllers control the valve states based on received signals from pressure sensors attached to the upper block 276, and in the case of a hemodialysis device, selectively operate the valves to provide programmed instructions for pumping blood, dialysate, and water to provide dialysis treatment to a patient.

[0066] The pressure distribution module 260 controls the operation of the pneumatically driven diaphragm pump and the pneumatically driven liquid valve 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. The digital valves can have two positions. The two-way digital valve can be opened or closed. The three-way digital valve connects a common port to either a first port or a second port. One or more controllers control the states of valves 262, 265, 267 (see FIG. 34) based in part on signals received by the one or more controllers from pressure sensor 565. The pressure reservoirs can include a high positive pressure reservoir, a low positive pressure reservoir, a negative pressure or vacuum reservoir, and a vent to the atmosphere.

[0067] The pressure distribution module 260 can be assembled from a plurality of manifold blocks. The pressure distribution manifold 260 in FIGS. 32 and 33 includes a T-shaped manifold block 272, an intermediate manifold block 274, and an end manifold block 276. The pressure distribution manifold 260 further includes a cartridge valve 265 mounted within the intermediate manifold block 274 and a surface-mounted valve 267 mounted on the vertical leg of the T-shaped manifold block 272. The arrangement of the pressure reservoir ports 263, the first set of valves 265, and the second set of valves 267 can be horizontal with respect to the faces 272F, 274F, and 276F (FIG. 33) belonging to the manifold blocks 272, 274, and 276, respectively. This configuration helps to avoid deposits of debris or liquid within the valves that could impair the function of the valves or reduce the maintenance-free lifespan. The pressure sensor 565 (FIG. 34) is mounted to a port 567 on the upward-facing opposing surface of the end manifold block 276. The adapters 266, 268, and 270 provide ports 266P, 268P, 270P for receiving the ports 240 of the cassette assembly 226.

[0068] The intermediate manifold block 274 and the T-shaped manifold block 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 along the entire length of the manifold blocks 272, 274. The ports for the internal supply lines are either capped 264 or have ports 263 for flexible tube connections to a pressure reservoir. Both end faces of the manifold blocks 272, 274 may include ports for connecting internal supply lines (not shown) to an external pressure reservoir.

[0069] A plurality of diaphragm pumps and diaphragm valves can be grouped into a single cassette as shown in FIGS. 6-13. A plurality of such cassettes can be joined together to form a cassette assembly 226 as shown in FIGS. 20 and 21. In this case, the assembly spaces the cassettes apart to accommodate outboard pumps, and the mixing chamber or fluid balance chamber has a volume larger than the volume that can be accommodated in any one of the individual cassettes. The pressure distribution module 260 includes adapters 266, 268, 270 that extend perpendicular to the long axes of the manifold blocks 272, 274, 276. The adapters expand the interface region of the pressure distribution module from the occupied regions of the manifold blocks and risers to any region necessary to receive the ports 240 of the cassette assembly 226. The pneumatic layout and port distribution on and within the adapters 270, 268, and 266 and their sub-components (not shown) enable a direct connection between the cassette assembly 226 and the manifold blocks 272, 274, 276 using a one-to-one mapping of each port of the cassette assembly to the corresponding working port of the manifold assembly.

[0070] An external pressure reservoir to which the pressure distribution module 260 can be connected can have a volume maintained at a specified pressure or a predetermined pressure by a pump controlled by a system controller. In one embodiment, the high-pressure reservoir can be maintained at a pressure of about 1050 mmHg, and the positive-pressure reservoir can be maintained at a pressure of about 800 mmHg. The pressure actually supplied to various pneumatic pumps and valves can vary based on the pressure reservoir ported by the two-way valve and three-way valve of the pressure distribution module 260. Further, the intermediate pressure can be supplied by a combination of rapid opening and closing of an on-off valve. Generally, a high-pressure source can be useful for actuating a diaphragm valve to ensure a reliable valve closure without leakage during operation of the cassette assembly.

[0071] Figure 33 shows an exploded view of the pressure distribution manifold 226. The manifold blocks 272, 274, and 276 can further include an intermediate element connection mechanism between each of the manifold blocks 272, 274, and 276. These intermediate elements and connection mechanisms can serve to assemble the three manifold blocks and establish a pneumatic connection between the individual manifold blocks 272, 274, and 276. The 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 the second set of intermediate components can include a second gasket plate 555, a third gasket 556, and a fourth gasket 558 disposed between the intermediate manifold block 274 and the end manifold block 276. The two manifold blocks 272, 274 can be clamped together with the gasketed intermediate plate 550 therebetween. The intermediate plate 550 can be referred to as a backing plate because it provides a rigid surface that forcibly seals the gaskets against a plurality of passages that can be provided on the end manifold block 276, the T-shaped manifold block 272, and the intermediate manifold block 274. Each manifold block 276, 274, 272 can include at least one face 276G, 274F, 272F (see FIGS. 33, 35, 36) having passages and various ports that mate with ported plates and gaskets (such as plates 550, 555 and gaskets 552, 554, 556, 558). The individual passages can be configured as grooves that include a solid bottom and two side walls having open tops. The passages can be cut into one face 276F, 274F, 272F of the manifold block or can be formed by walls that extend above the surfaces of the manifold block faces 276F, 274F, 274G, and 272F. As shown in FIG. 33, the open tops of the passages can be sealed by clamping the gaskets 554, 552, 556, 558 that are lined by the rigid flat intermediate plates 550, 555 against the passages.In one example, the intermediate plate 550 is a backing plate that presses the gasket 552 against all the passages on the surface 272F and biases the gasket 554 against the passages on the surface 274G. Note that the surface 274G is on the opposite side of the surface 274F in FIG. 33. The manifold block and the gasket can include a mechanism that ensures an essentially uniform distribution of pressure to the gasket. The intermediate plate 550 provides a substantially smooth and rigid backing for the gasket, such that a plurality of manifold blocks are assembled or sandwiched within the multi-component pneumatic manifold 260. The passages are linked to pressure sources, valves, sensors, and outlet ports on other faces of the block. The manifold blocks 276, 274, 272 sandwich the gaskets 552, 554, 556, 558 and the intermediate plates 550, 555 therebetween by mechanical fasteners 570 to seal a plurality of passages on the surfaces 272F, 274F, 274G, 276G on which the passages of each of the manifold blocks 272, 274, 276 are formed. This sandwich structure enables a compact assembly of a plurality of manifold blocks each having a plurality of sets of passages on one side of each block 272, 274, 276.

[0072] The connection points of the T-shaped manifold block 272 can be configured to receive screws that extend through other components for assembling the pressure distribution manifold 260 as a unit. In this example, matching connection points 572 can be provided on the first gasket plate 550, connection points 573 on the intermediate manifold block 274, and connection points 573 on the third and fourth gaskets 556, 558. The first set of valves 265 can operate on the pneumatic paths within the manifold blocks 272, 274, and 276 and / or on the pneumatic paths connecting the manifold blocks 272, 274, and 276.

[0073] Figures 32 and 33 illustrate an embodiment that includes a plurality of cartridge valves 265 and connections to a pressure reservoir 263. The cartridge valves are inserted into manifold ports. Corresponding cavities (not shown) are formed to accommodate seals outside the cartridge valves 265. The machined cavities may have a set of dimensions specified by the valve manufacturer to ensure sealing and proper functioning of the cartridge valves 265. In other embodiments, the number may vary, but in this particular embodiment, approximately 48 cartridge valves 265 are attached to the side surface of an intermediate manifold block 274. This side surface of the intermediate manifold block 274 is perpendicular to the surface 274F in which the passage is formed. In some embodiments, the cartridge valves are three-way valves such as the Lee LHDA plug-in valve available from the Lee Company of Westbrook, Connecticut, USA. The number of electromechanical valves is determined by the number of individual diaphragm pumps and valves operated in the direct connection cassette assembly and the remote connection cassette assembly (if required), and the linear arrangement of the electromechanical valves will extend the length of the manifold assembly.

[0074] Referring now to FIG. 34, the pressure distribution manifold can function as a pneumatic actuator for components other than the cassette assembly 226. For example, the pressure distribution manifold 260 can also be pneumatically connected to other pneumatically driven valves, diaphragm pumps, pneumatic cylinders, and remote cassettes including diaphragm valves and diaphragm pumps. In one example, the pressure distribution module 260 controls the position of the occluder 251 in FIG. 23, and the occluder includes a pinch valve for blocking the blood line and is driven by a pneumatic cylinder. In another example, the pressure distribution module 260 can be arranged to be pneumatically connected to the dialysate tank to perform volume measurement of the tank using pressure information. Further, the pressure distribution module 260 can be configured to control the pumping operation of a blood pump cassette (not shown) attached to the blood pump cassette receptacle assembly 252 in FIG. 23. Referring now to FIG. 34, the port 582 shown in the T-shaped manifold block 272 can be directly connected to one or more blood pump cassettes or connected via a flexible or malleable tube to establish the necessary pneumatic connections. The port 582 includes a fitting that can be connected to a pneumatic tube and is individually removable from the T-shaped manifold 272. One end of the pneumatic line connected to the port 582 can be connected to a connector on the surface of the wall 255 (FIG. 24) of the dialysis device. A second connector within the housing can be connected to, for example, the dialysate tank, a pneumatically actuated tubing occluder, and / or the blood pump cassette receptacle assembly 252 using flexible tubing.

[0075] The cartridge valve 265 and the surface-mounted valve 267 in this embodiment control the pneumatic pressure supplied to the occluder, the blood pump cassette, and other pneumatically driven components within the hemodialysis device 246. Mounting mechanisms such as standoffs 580 for attaching the pressure distribution module 260 to the rear wall of the enclosure 254 and setting the positions of the adapters 266, 268, 270 relative to the enclosure 254 can be provided.

[0076] Continuing to refer to FIGS. 34 and 35, the valve 267 disposed on the T-shaped manifold block 272 is an electromechanical valve that seals against a flat surface or a surface machined to receive the valve face. In some embodiments, the surface-mounted valve 267 can be a proportional valve or a continuously variable valve (also referred to as a "variable valve"). In other embodiments, the surface-mounted valve 267 is a binary two-way valve or a three-way valve. In some examples, the surface 272F is substantially horizontal, such that the legs of the T-shaped cross-section of the manifold 272 are substantially vertical. In a preferred configuration, the valve mounting surface of the leg is vertical or slightly inclined upward, such that the ports on the valve 267 are inclined horizontally or downward to avoid accumulation of waste or liquid. To prevent leakage of fluid or air, a sealing mechanism such as an O-ring and / or other elements can be provided on the valve. The valve 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 of Parker Hannifin Corporation of Hollis, New Hampshire, USA.

[0077] Referring now to FIG. 34, the pneumatic flow on the pressure distribution manifold 226 can be monitored via one or more pressure sensors, which can be mounted on a sensor board (e.g., a PCB). In this example, the sensor board 560 can be disposed on the surface 567 of the upper manifold block 276 in the space between the risers 276A - C. The pressure sensor 565 can be mounted directly on the face 276F of the first end manifold block 276. The pressure sensor 565 can be an integrated circuit soldered to a printed circuit board (PCB) 560. As shown in FIG. 34, the printed circuit board 560 including one or more pressure sensors 565 is placed on the upper face 276F parallel to the face in which the passage of the second end manifold block 276 is formed, with a gasket for pneumatically isolating each sensor and a plate (not shown) for holding the PCB 560 in place and sufficiently compressing the gasket to seal each pressure sensor from the atmosphere. The sensor board 560 can be coupled to the surface 567 of the end manifold block via fixing components such as screws, nut - bolt pairs, rivets, adhesives, or combinations of such fixing mechanisms. An example of the pressure sensor 565 can be obtained from Freescale Semiconductor, Inc. (part number MPXH6250A) in Tempe, Arizona, USA. The PCB including multiple pressure sensors 565 can be mounted as a unit to the end manifold block 276. The pressure sensing surface of each pressure sensor 565 can be fluidly connected to a desired pressure source such as a reference volume or more remotely to the operating chamber of a diaphragm pump or a dialysate reservoir tank. In some cases, the sensors are arranged to monitor the liquid pressure of various diaphragm pumps in a fluid processing cassette. The end manifold block 276 includes risers 276A, 276B, and 276C that can interface with the individual adapters 270, 268, and 266. The manifold assembly is configured to avoid the engagement between the sensor board 560 and the corresponding adapter of the riser.The riser also provides separation between the fluid processing cassette assembly described above and the temperature sensing sensor board 560, thereby enabling the placement of a heat insulating material 269A therebetween (see, for example, FIG. 48).

[0078] FIGS. 36 and 37 show a second manifold block 276 having a face 276F and a base surface 276G. The base surface 276G can be configured to mate with one or more intermediate components such as gaskets, gasket plates, and / or other manifold blocks. As shown, the base surface 276 can include a plurality of pneumatic passages 574 sealed by a gasket 558 (FIG. 33). In some examples, the passage 574 can connect a pressure port 567 on the face 276F to the holes 261A, 261B, 261C of the riser. In other examples, the passage 574 can connect a pneumatic path or hole to either the pressure port 567 or one of the holes 261A, 261B, 261C via the gasket 558. The face 276F can include risers 276A, 276B, and 276C that can each function as attachment surfaces for corresponding adapters 270, 268, and 266. The pneumatic ports 261A, 261B, and 261C on the risers 276A, 276B, and 276C can interface with the individual adapters 270, 268, and 266 to transmit pneumatic pressure to the cassette assembly 226. The fixed connection between the riser port 261 and the adapter can be established via a mechanical fixture such as a nut-bolt pair, a screw-on or press-on type, or a similar mechanism. The mechanical assembly can also include mating the block with intermediate parts such as one or more gaskets 568 (FIG. 32), gasket plates, and / or similar components.

[0079] Pneumatic connection in the manifold The structure and function of the manifold 260 in FIG. 32 can be further understood by considering the pneumatic source, conduits, valves, sensors, and outlet ports of the manifold 260. In the example illustrated in FIG. 32, the manifold 260 has dozens of valves, sensors, and ports. In the following section, the pressure source, valves, conduits, ports, and three exemplary paths including a pressure sensor in one example will be described. The exemplary paths serve to explain how the elements of the manifold in FIGS. 32 and 33 are combined to provide a selectable fluid connection between the pressure source and the actuating chambers of the pneumatic valves and pumps, and to provide a fluid connection to the pressure sensor. The pressure sensor provides information to a controller that controls the valves to safely pump blood, dialysate, and water to provide treatment to a patient.

[0080] The schematic diagram of the pneumatic manifold in FIG. 38 shows the pneumatic connection to the blood pump cassette (in this case, since the blood pump cassette is located on the front panel of the dialysis unit, it is connected to the manifold using a flexible tube rather than a direct connection). The pneumatic circuit in FIG. 38 selectively connects the actuating chamber of the blood, the heparin pump, and the 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, to the low pressure source LP via the valve V_BP_POS1, and to the negative pressure source NEG via the valve V_BP_NEG1.

[0081] The blood pump operation circuit 1005 within the manifold 260 is shown in FIGS. 39 and 40. The flow paths are the holes and passages of the various blocks of the manifold 260. The low pressure source LP is a conduit within the horizontal portion 272A of the T-shaped manifold that extends along the length of the T-shaped manifold block 272. The negative pressure source NEG is a conduit parallel to LP that passes through the major axis of the T-shaped manifold block 272. The positive pressure flows from the LP conduit, through the flow path 1012 disposed at the top of the T-shaped manifold 272, and then through the hole 1020 that passes through the vertical leg 272B of the T-shaped manifold, and flows to the electromechanical valve V_BP_POS1. When the valve V_BP_POS1 opens, the positive pressure flows through the hole 1025 in the vertical leg 272B and into the passage 1040 disposed at the top of the T-shaped manifold 272. Next, the low pressure flows through the hole 1060 to the port 582, where the fitting allows a flexible or malleable line to connect the port to the (remote) blood pump cassette. The pressure within the blood pump connected to the port 582 is monitored by a pressure sensor attached to the port P_BP1. The port BP1 is disposed below the two upward-facing surfaces of the upper manifold block 276. The port P_BP1 is fluidly connected to the passage 1040 via the hole 1057 in the upper manifold block 276, the upper passage 1055 in the intermediate manifold block 274, and the hole 1050 passing through the intermediate manifold block 274.

[0082] In circuit 1005, which is shown embedded in manifold assembly 260 in FIG. 40, the T-shaped manifold block 272 selectively connects the working chamber of the blood pump cassette (inserted into cassette receptacle 252 of FIG. 23) to either a low-pressure source LP or a negative-pressure source NEG via two valves. The pressure sensor attached to the upper manifold block 276 is fluidly connected through the holes and passages of the upper and intermediate manifold blocks. Other pneumatic circuits can connect the working chamber for the diaphragm pump within cassette assembly 226 to two of the low-pressure source LP, the atmospheric-pressure source ATM, and the negative-pressure source NEG via a valve on the vertical leg 272B of the T-shaped manifold block 272.

[0083] The schematic diagram of the pneumatic pressure in FIG. 41 illustrates the pneumatic connections to various working ports of cassette assembly 226. The pneumatic circuit in FIG. 41 selectively connects the working chambers of various valves (and the two diaphragm pumps shown here) on the external dialysis fluid cassette (ODC) to at least one of the atmospheric-pressure source ATM, the high positive-pressure source HP, the low positive-pressure source LP, and the negative-pressure source NEG. Circuit 1100 is an example of a pneumatic circuit that connects the diaphragm valve V_MIX_DT within the ODC cassette to either the ATM or the LP pressure source via a three-way valve 1105. Circuit 1200 is an example of a pneumatic circuit that connects the liquid valve V_DISINECT within the ODC cassette to either the HP pressure source or the NEG pressure source via a three-way valve 1205.

[0084] The Mix_DT valve circuit 1100 and the DISINFECT valve circuit 1200 within the manifold 260 are shown in FIGS. 42 and 43. The flow path includes holes and passages in various blocks of the manifold 260. The pressure sources ATM, NEG, LP, HP are conduits arranged along the long axis of the intermediate block 274. The MIX_DT circuit 1100 connects either the low-pressure source LP or the atmospheric pressure source ATM to the outlet port V_MIX_DT of the MIX_DT liquid valve within the cassette assembly 226. The low-pressure source LP is connected to the valve 1105 via the passage 1110 and the hole 1115 on the bottom surface of the intermediate manifold block 274. The atmospheric pressure source ATM is connected to the valve 1105 via the passage 1140 and the hole 1145 on the bottom surface of the intermediate manifold block 274. The valve 1105 is connected to the outlet port V_Mix_DT via the passage 1120 on the upper part of the intermediate manifold block 274, the hole 1130 through the upper manifold, and the hole 1135 through the adapter 268.

[0085] The DISINFECT circuit 1200 connects either the high-pressure source HP or the negative pressure source NEG to the outlet port V_DISINFECT of the DISINFECT liquid valve within the cassette assembly 226. The high-pressure source HP is connected to the valve 1205 via the passage 1210 and the hole 1215 on the bottom surface of the intermediate manifold block 274. The negative pressure source NEG is connected to the valve 1205 via the passage 1240 and the hole 1245 on the bottom surface of the intermediate manifold block 274. The valve 1205 is connected to the outlet port V_DISINFECT through the adapter rail 268 via the passage 1220 on the upper part of the intermediate manifold block 274, the hole 1222 through the intermediate manifold 274, the passage 1224 on the bottom of the intermediate manifold, the hole 1226 returning through the intermediate manifold, the passage 1228 on the upper part of the intermediate manifold, the hole 1230 through the upper part of the upper manifold 276, and the hold 1235 and the passage 1237.

[0086] Figure 43 shows how the above circuit is physically embedded within the manifold assembly 260. Also shown is the mapping of these actuating ports from an array on riser 276B to a spatially different array of actuating ports of manifold adapter 268, providing an actuating port array that matches the actuating port array of cassette assembly 226.

[0087] Figure 44 shows the pressure distribution manifold 260 installed in the recess 258 of the enclosure or housing 254. This configuration enables proper alignment between the ports 261 on the riser of the pressure distribution manifold 260 and the individual ports on the mating surfaces of adapters 266, 268, and 270. In this embodiment, the manifold 260 is disposed under some thermal insulation 264. The thermal insulation 264 can be provided between the body of the manifold 260 and the shelf 256. This configuration isolates temperature-sensitive electronics from the heated fluid circulating within components in the enclosure or housing 254.

[0088] As shown in FIG. 45, in this embodiment of the hemodialysis device 246 and the enclosure 254, the occupied area of the cassette assembly 226 extends forward from the front surface of the device 246. With respect to the user or operator facing the hemodialysis device 246, the occupied area of the cassette extends beyond the front edge of the shelf 256. For this reason, one or more adapters 266, 268, 270 are configured to provide the necessary mating of the operating ports 240 of the cassette assembly 226 with the individual connectors or receptacle ports 266P, 268P, and 270P disposed on the interface or adapters 266, 268, 270. The adapters 266, 268, 270 in this example function as a receptacle assembly and provide a first spatial arrangement of receptacle ports that mate with the identically arranged cassette ports 240 of the individual cassettes 194, 196, and 198 of the cassette assembly 226. FIG. 46 shows a bottom perspective view of the enclosure 254 attached to the interface / adapters 266, 268, 270. In this figure, it is clear to what extent the adapters project beyond the enclosure shelf 256 (and thus the underlying pressure supply manifold 246).

[0089] FIG. 32 shows how the adapters 266, 268, 270 are attached to the top side of the manifold driers 276A - C and how they project beyond the front side of the manifold 260. The first spatial array of receptacle ports 266P, 268P, and 270P connects to a second (in this case, more compact) spatial array of the output ports 261 of the upper block or driers 276A - C of the manifold 260. The internal passages within the adapters 266, 268, 270 are routed to the individual driers 276A, 276B, and 276C mounted on top of the corresponding array of manifold output ports. FIG. 52 shows a manifold / adapter assembly with the adapter 266 removed and disassembled, fully revealing the structure of the adapter as well as the driers 276C, 276A, and 276B.

[0090] Figs. 47 and 48 are rear views of the manifold 260, showing that the risers 276A, 276B, and 276C can slide the adapters 266, 268, and 270 to individual positions within the enclosure 254 through slots or cutouts 280, 282, 284 in the shelf 256 of the enclosure 254 from the rear of the enclosure. The risers 276A, 276B, and 276C are made to a height sufficient to allow placement of a heat insulating material (either a rigid foam insulating material or some other type of insulating material) between the shelf 256 and the body of the manifold 260 and to provide a thermal barrier to electronic components (control boards, sensors, etc.) disposed in the recess 258 (see, for example, the insulating material 269A wrapped around the riser in Fig. 48). Fig. 48 shows a method of sliding an assembly including the manifold 260, its attached risers and adapters 266, 268, and 270, and other related components as a group to a predetermined position within the recess 258 of the enclosure 254.

[0091] Figures 49 through 51 show the engagement between the adapters and their respective rails. The adapters are disposed within the enclosure to receive a cassette assembly from a cassette loading device within housing 254. Adapter receptacles or adapter rails 591, 593, and 595 can be integrated with the shelf 256 of the enclosure 254 or can be separate components that can be mechanically attached to the enclosure 254. In one embodiment, the shelf 256 includes a space for receiving or attaching the adapter rails 591, 593, 595. FIG. 48 specifically shows a rear (outer) view of the enclosure 254 with the adapters 266, 268, 270 partially inserted into the respective adapter rails 595, 593, and 591 (shown in FIG. 49). The manifold 260 is attached to the adapters 266, 3268, 270 before the manifold / adapter assembly is slid to its final position within the enclosure 254 defined by the adapters and the adapter rails. As shown in FIG. 49, the rails 591, 593, and 595 are disposed within spaces 591S, 593S, and 595S, respectively. FIG. 49 shows a front (inner) view of the adapters 266, 268, and 270 partially received within the individual adapter rails within the enclosure 254.

[0092] The proper alignment of 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 matching receptacle ports 266P, 268P, 270P to provide the necessary pneumatic connections to the cassette assembly 226. The final placement of the adapters is defined by adapter rails that are securely attached to the same enclosure in which the cassette loader 292 is attached to the roof of the enclosure 254. As a result, the retaining mechanism for the above components should be appropriately arranged to achieve alignment of the pneumatic ports among the three assemblies, namely, the cassette assembly 226, the adapters 266, 268, 270, and the pneumatic manifold 260. FIG. 50 shows a cassette loader 292 with an operating handle 308. The cassette loader 292 can be attached to the inner surface of the roof 604 of the housing or enclosure 254. As shown, the cassette loader 292 and the adapter rails 591, 593 and 595 are disposed on opposing surfaces of the enclosure 254 and maintain a fixed spatial relationship with each other.

[0093] FIG. 51 shows an exemplary adapter rail 591 that can include a headrest or flange 592 and a tray portion 587 having a raised platform 596, the raised platform 596 being able to partially or fully occupy a tray portion 597. The headrest 592 forms the frame of the rail 591 together with the tray portion 597. The tray portion 597 can receive a corresponding adapter, and the corresponding adapter can be placed on the raised platform 596. The tray portion 597 can also include a grating profile 594, and the grating profile 594 can be curved according to the end of the corresponding adapter received within the rail 591 such that the adapter can slide into the receiving rail. In this embodiment, the tray portion 597 can further include a cutout region 597 where the received adapter can interface with a corresponding riser on the pneumatic manifold 260. An elongated slot or groove 611 can optionally be provided between the side of the raised platform 596 and the grating profile 594. The elongated groove 611 serves to collect any leaked liquid that risks reaching electronics located under the shelf 256 or in the recessed area 258 and to keep any leaked liquid or condensation away from the upper surface of the installed adapter.

[0094] Figures 52 and 53 show exploded views of the interaction of exemplary adapter 266 and its corresponding riser 276C. More specifically, FIG. 52 shows a top view of a plurality of plates and gaskets that can collectively form adapter 266. Also, FIG. 53 shows a bottom view of the same exploded view of adapter 266. The adapter is arranged to provide individual pneumatic paths between the first port array of cassette assembly 226 and the second port array of pneumatic manifold 260. In this example, the pneumatic ports 240 on the cassette assembly are dispersed over an extended surface area that is wider than the narrow dimensions of manifold assembly 260. The adapter functions to converge a first, larger space array into a smaller space array of pneumatic ports 261 on the riser of manifold 260. As shown in FIGS. 52 and 53, exemplary adapter 266 can include a plurality of layers or plates that include pneumatic openings and passages that converge to a smaller surface area as the layers proceed towards the individual risers. The upper plate 280 of adapter 266 includes a pneumatic port 271 and a connection mechanism for engaging subsequent plates of the adapter. Pneumatic port 271 and connection mechanism 293 can be seen through the top view of upper plate 280 in FIG. 52 and the bottom view of upper plate 280 shown in FIG. 53. Upper plate 280 is placed on an intermediate block 286 that includes corresponding pneumatic ports 285 on a first surface 286A. These pneumatic ports 285 align with pneumatic ports 271 on upper plate 280. Wiper gasket 282 is received in a gasket receptacle 281 recessed in the first surface of intermediate block 286. Continuous elastomeric gasket 282 has a properly positioned wiper seal 284 and can be formed from a mold. Wiper seal 284 provides sufficient sealing engagement between cassette port 240 and corresponding adapter receptacle port 271 while having a lower frictional resistance to the attachment and removal of cassette assembly 226 than, for example, individual O-ring seals.

[0095] FIG. 53 shows the second opposing surface 286B of the intermediate block 286. This surface includes a pneumatic passage 286C that is in fluid communication with the port 281 on the first surface 286A. The passage 285C can be arranged to converge and connect the pneumatic port 281 on the first surface 286A to the dispersed pneumatic ports on the second surface 286B. As shown, the pneumatic ports on the second surface 286B occupy a smaller area and a different spatial array compared to the pneumatic ports on the first surface 286A. The passage 285C ensures that the pneumatic port 281 converges or shifts towards the port array on the riser side of the adapter 266. The second intermediate block 290 can include a pneumatic port 288 that coincides with the array of pneumatic ports provided on the second surface 286B of the intermediate block 286. The second gasket 289 can be disposed between the first intermediate block 285 and the second intermediate block 290. The gasket 289 allows for an appropriate seal between the first intermediate plate 286 and the second intermediate plate 290 and enables the gasket to be compressed to the extent necessary to form the seal. In one embodiment, a set of alignment mechanisms can be provided on the gasket 289 and on one or both of the adjacent plates. In this case, the plates can be the first intermediate block 286 and the second intermediate block 290. Further, the transitional gasket 289 can include pneumatic ports corresponding to the pneumatic port 285 on the first intermediate block 286 and the pneumatic port 288 on the second intermediate block 290. The riser gasket 291 can be disposed between the second intermediate block 290 and the corresponding riser (riser 276C in this example). This gasket is arranged to seal the interaction between the second intermediate block 290 and the riser 276C. A plurality of gasket alignment mechanisms can be provided on the mating surfaces of the second intermediate block 286 and the riser 276C. The foregoing description is intended to be applicable also to the adapters 268, 270, and the interacting risers 276B and 276A.The number and spatial distribution of pneumatic ports in embodiments of the interaction of other adapter-risers can be made different, and they are different in this embodiment.

[0096] When there is a pneumatic interaction between ports, the sealing component between the ports usually includes an O-ring. In the case of an adapter, multiple O-rings can be used to ensure a sealing engagement between mating ports. However, multiple spatially arranged O-rings may exhibit a relatively low alignment tolerance when multiple pneumatic ports 240 are inserted into the corresponding adapter ports. In addition to the tolerance problem, multiple O-ring connections may generate more engagement / disengagement force than desired between the cassette assembly 226 and its associated adapter. In another configuration, the web of the wiper gasket can be used to form the necessary seal and can be attached between two interacting plates or blocks of the adapter. FIG. 53 shows an exemplary wiper gasket 284 that can be molded as a single unit, thereby substantially simplifying the assembly and installation procedures. FIG. 54 shows an exemplary wiper gasket used in one of the manifold adapters. FIG. 55 shows Along the 33H-33H line Cross-section of the wiper gasket of FIG. 54 Figure is shown. As shown, the gasket 284 can be formed to annularly surround the port 285 and form a conical peripheral recess towards the pneumatic port 285. The gasket 284 can optionally include an annular nodule or ridge 283 constructed on the wiper gasket 284 to cover a portion of the port 285. This configuration and structure of the wiper gasket 284 may allow the insertion of the cassette port 240 with an acceptable amount of force and ensure a seal between the adapter and the cassette during operation (i.e., while applying positive and negative pressures through the ports of the adapter).

[0097] Figures 56 and 57 show a cassette seating device or cassette loader 292 that is used to fix the first side of the cassette assembly 226 so as to move the cassette assembly linearly toward or away from one or more arrays of receptacle assemblies that are arranged to mate with a corresponding array of cassette ports 240 on one or more of the cassettes 228, 230, and 232 on the opposite second side of the cassette assembly 226. In the example described below, the receptacle assembly includes manifold adapters 266, 268, 270, but the cassette loader can be used in any other system where a ported cassette is inserted into and removed from any type of receptacle array, including, among other things, a fixed multi-port receptacle or a movable connector with an array of ports. The receptacle ports to which the cassette operating ports are connected can be placed directly on the frame, on the housing, or on the manifold output port array, rather than the exemplary adapters 266, 268, 270 shown, if two sets of mating ports can be arranged to be properly aligned. The cassette seating device 292 has general utility in assisting a cassette having external ports to engage or disengage from a mating connector or receptacle port on any device.

[0098] Figure 56 shows the cassette loader 292 in the storage position, and the cassette loader 292 moves the cassette assembly linearly away from the ports 271 of Figure 52 that are arranged on the adapters 266, 268, 270, more generally, in this example, the receptacle ports 261b of Figure 29, or the ports 266P, 268P, and 270P of Figures 30, 32, and 45. Note that the cassette seating device or cassette loader 292 can be used to seat a cassette or cassette assembly onto a receptacle assembly or to disengage it from the receptacle assembly as long as the single cassette or group of cassettes has either a liquid port or an operating port on the side opposite the side fixed by the cassette seating device 292.

[0099] In this example, the cassette seating device 292 includes a fixed frame 294 including fixed members 296a, b. The fixed members 296a, b are coupled to a link mechanism that interacts with the movable cassette mount 298. The movable cassette mount 298 is configured to hold a cassette or a cassette assembly and, in this example, includes flanges 300a, b that connect to cassette mount rails 302a, b. In this example, the cassette mount rails 300a, b allow the cassette or cassette assembly to be slid and held in a predetermined position on the seating device 292. Other examples can include a clamping device that can grip the cassette or cassette assembly. In this example, the independent movement of the attached cassette or cassette assembly is restricted by the presence of one or more cross members 304 that limit movement on the upper surface side of the attached cassette or cassette assembly, and by actuator arms 306a, b of the operation handle 308, which move to positions that impede the lateral movement of the attached cassette or cassette assembly.

[0100] As shown in FIGS. 56 to 58, the link mechanism can include two or more swing arms 310a, b, and each of the swing arms is pivotally connected to the fixing members 296a, b at the first end 312. Each of the swing arms 310a, b is arranged to move in a plane substantially parallel to the moving direction of the cassette mount 298 with respect to the fixing members 296a, b. The second end of each of the swing arms 308a, b includes a hub 316 coupled to a shaft or pinion 318, and the shaft / pinion is configured to interact with a flange 300a or 300b generally parallel to the movement plane of the swing arms 310a, b. The shaft or pinion 318 is disposed within the elongated slot 320 of the flange 300a or 300b, and the elongated slot 320 converts an arcuate movement towards or away from the fixing members 296a, b at the second end of the swing arms 310a, b into a linear movement towards or away from the fixing members 296a, 296b of the cassette mount rails 302a, 302b. In this example, the shaft or pinion 318 optionally extends from the flange 300a to the flange 300b and also functions as a cross member 304. The shaft or pinion 318 can slidably interact with the slot 320 or by other means (e.g., via a circular bearing or wheel disposed in the slot 320).

[0101] To assist in ensuring the linear movement of the cassette mount 298, one or more guide elements (e.g., posts 322, etc.) can be optionally included to restrict the lateral movement of the cassette mount 298 and its attached mount rails 302a, b. The guide element 322 can be rigidly attached to or mounted on the fixed frame 294 (or alternatively the fixed members 296a, b) and can extend in the desired direction of movement of the cassette mount rails 302a, b. The guide element 322 can interact with the cassette mount 298 (or alternatively the flange 300a or 300b, or the mount rail 302a or 302b) via a guide hole 324 (or a guide rail, track or other element), and this guide hole 324 restricts the relative movement of the cassette mount 298 in the front-rear direction with respect to the frame 294 or the fixed members 296a, b.

[0102] FIG. 56 shows the cassette seating device 292 in a substantially fully retracted position, where the cassette mount 298 is retracted away from a receptacle assembly that is sufficiently associated to disengage the cassette actuation (or fluid) ports of the attached cassette from the individual receptacle ports (see, e.g., FIGS. 30 and 31). FIGS. 57-59 show the cassette seating device 292 in an engaged position, where the cassette mount is linearly extended away from the fixed frame 294 or the fixed members 296a, 296b sufficiently to engage the cassette actuation (or fluid) ports of the attached cassette with their corresponding receptacle ports. The actuator arms 306a, b of the handle 308 are pivotally connected to the fixed members 296a, 296b at their distal ends 326. Each actuator arm 306a, b is also pivotally connected to the first ends of the connecting members 330a, b at a more proximal portion 328 of the arms 306a, b. Next, the second ends of the connecting members 330a, b are pivotally connected to an actuator bar 332 having a pivotal connection to the second ends of each swing arm 310a, b including the linkage mechanism of the cassette seating device 292. The connecting member 330a or 330b moves eccentrically with respect to the axis of rotation of the actuator arm 306a or 306b, thereby displacing the actuator bars 332a, b and the swing arms 310a, b away from the fixed members 296a, 296b.

[0103] Optionally, the cassette mount retaining member 334 can be used to hold the cassette mount 298 in its storage position. In one example, the cassette mount retaining member 298 can include a pawl that is pushed aside by the cross member 304 (alternatively, another element attached to the cassette mount 298, flange 300, rail 302, or shaft / pinion 318) when the handle 308 is fully retracted into its storage position (see FIG. 56). When the cross member 304 reaches the recess 336 of the pawl, the pawl descends and engages the cross member 304 to hold the cassette mount 298 in its storage position. In additional or alternative embodiments, the handle 308 can include a movable plunger element (alternate to the handle post 338 (see FIGS. 57, 59)) that can engage or pass through a hole or recess (not shown) in the 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.

[0104] As applied to the hemodialysis enclosure 254 (see FIG. 23), the cassette seating device 292 can be mounted to the ceiling inside the enclosure 254 as shown in FIGS. 45 and 46. This is located on the opposite side of the receptacle assemblies 266, 268, 270 (in this case, the manifold adapter). The cassette assembly 226 can be seen to be installed on the cassette seating device 292 by the cassette assembly frame plate 513, for example, as shown in FIGS. 21 and 46. In FIGS. 30 and 31, the cassette assembly port 240 is shown to be directly adjacent to the corresponding receptacle port on the receptacle assembly and is fully disengaged from the receptacle port when the handle 308 is placed in its storage position (FIG. 30).

[0105] Pneumatic pump system using binary valve FIG. 60 is a schematic view showing an embodiment of a pressure actuation system 14000 for a positive displacement diaphragm pump (a "pod pump") 234 as shown in FIG. 20. In this example, pneumatic pressure is used as the control fluid (e.g., such that the pump is driven by pneumatic pressure). In other embodiments, other fluids (e.g., water or a water-based solution) may also be used as the control fluid.

[0106] In FIG. 60, the pressure actuation system 14000 alternately supplies positive and negative gas pressures into the working chamber 14020 of the pod pump 23a. The pneumatic actuation system 14000 includes a working chamber pressure transducer 14020, a positive supply valve LP1, a negative supply valve N1, a positive gas source LPOS, a negative gas source NEG, a positive source pressure transducer (not shown), a negative source pressure transducer (not shown), and an electronic controller 14035. The electronic controller receives pressure data from the pressure sensor 14020 and controls 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 may be used instead 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 that are either fully open or fully closed.

[0107] The positive gas source LPOS supplies positive pressure control gas to the working chamber 14020 to bias the diaphragm 14025 towards a position that minimizes the volume of the pumping chamber 14027 (i.e., the position where the diaphragm abuts against the rigid wall of the pumping chamber). The negative gas source NEG supplies negative pressure control gas to the working chamber 14020 to bias the diaphragm 14025 in the opposite direction towards a position that maximizes the volume of the pumping chamber 14027 (i.e., the position where the diaphragm faces the rigid wall of the working chamber).

[0108] Controller 14035 can also receive pressure information from three other pressure transducers (the working chamber pressure transducer 14020, the transducer on LPOS, and the transducer on NEG). As their names indicate, these transducers measure the pressures within the working chamber 14020, the positive pressure source LPOS, and the negative pressure source NEG, respectively. Controller 14035 monitors the pressures within the two pressure sources LPOS and NEG to confirm that they are properly pressurized (either positively or negatively). A compressor-type pump can be used to maintain the desired pressure in the reservoirs containing the pressure sources LPOS and NEG.

[0109] In one embodiment, the pressure supplied by the positive pressure reservoir LPOS is in a normal state large enough to fully bias the diaphragm 14025 against the rigid wall of the pumping chamber. Similarly, the negative pressure (i.e., vacuum) supplied by the negative pressure source NEG is preferably, in the normal state, large enough to fully bias the diaphragm against the rigid wall of the working chamber. However, in a preferred embodiment, the positive and negative pressures supplied by the pressure sources LPOS and NEG are kept within a sufficient safety margin to avoid excessive liquid pressures that could harm a patient to whom the pump system may be connected.

[0110] Controller 14035 monitors the pressure information from the working chamber pressure transducer 196 and, based on this information and optionally a timer, controls the valve mechanism (valves LP1, N1) to fully bias the diaphragm 14025 to its minimum pumping chamber volume position and then switch the pressure to fully retract the diaphragm 14025 to its maximum pumping chamber volume position.

[0111] The pressure - actuated system comprises a pressure - distribution manifold that may include an actuation - chamber pressure transducer 14020, a transducer for the LPOS source, a transducer for the NEG source, a positive - supply valve LP1, and a negative - supply valve N1. The controller 14035 may be mounted on the manifold, and the positive - pressure gas source LPOS and the negative - pressure gas source NEG may include conduits that penetrate the manifold. The manifold can be configured to fit entirely or mostly within the recess 258 of the hemodialysis housing (see, for example, FIGS. 44 and 48). In this configuration, components that contact blood or dialysate (i.e., the pod pump 23a, the inlet valve 192, and the outlet valve 193) may be placed within an insulated enclosure 254 or a front panel 248 (see FIG. 23) so that the pumps, valves, and interconnecting liquid paths can be more easily accessed and / or sterilized.

[0112] Pump process using binary valve The process of pumping liquid through the pod pump 23a can be better understood by referring to FIGS. 61 and 62. Referring now to FIG. 61, the target pressure 14050 and the actual pressure 14055 measured by the pressure sensor 196 (FIG. 60) are plotted against the time of one pumping stroke and one filling stroke. The pumping stroke involves using the positive pressure from the LPOS source to drive the diaphragm 14025 from one side of the pump pod 23a to the other, discharging the liquid within the pumping chamber 14027. In contrast, the filling stroke involves using the sub - atmospheric pressure from the NEG source to pull the diaphragm 14025 back across the pod pump 23a and fill the pod pump with liquid. In some examples, the filling stroke is completed by connecting the actuation chamber 14020 to the atmosphere, enabling the liquid pressure within the system to drive the diaphragm across the pod - pump chamber.

[0113] In the binary valve driven pump 14000, the delivery and filling pump strokes include a plurality of charge cycles that generate the jagged pressure trace 14050 of FIGS. 61 and 62. The details of the start of the delivery stroke are shown in FIG. 62. In this figure, during the movement of the liquid, the actual pressure 14055 rises when the valve LP1 is open and the actual pressure 14055 drops when the valve LP1 is closed. In the delivery stroke, the movement of the liquid from the pumping chamber 14027 reduces the volume of the pumping chamber, and since the total volume of the pod pump is fixed, this increases the volume of the working chamber 14020. When the volume of the working chamber increases, the pressure in the working chamber drops if the pneumatic valve LP1 is closed. The charge cycle includes a pressure increase due to the valve being open and a pressure decay when the valve is closed. The length of the charge cycle can vary as shown in FIG. 62. Here, three complete charge cycles are shown, each with a different duration. FIG. 62 plots the details of the delivery stroke with positive pressure applied. Now, referring to the filling stroke for FIG. 61, the pressure trace 14055 has a similar jagged pattern. However, during the filling stroke, when the N1 valve is opened, the pressure drops rapidly, the working chamber is exposed to the NEG pressure source, and when the N1 valve is closed, it slowly recovers towards atmospheric pressure. Also in this case, the charge cycle includes a sharp increase in the magnitude of the working chamber pressure and a slower pressure decay to atmospheric pressure when the N1 valve is closed.

[0114] In conventional applications and disclosures, a continuously variable valve has been used to control a diaphragm pump, but herein, a binary valve is described that is either fully open or fully closed and not designed to open partially. Binary valves and associated control electronics are generally less expensive than variable open valves. Further, binary valves may require less functional checking / monitoring and may be less sensitive to the presence of debris in the pneumatic passages leading to or away from them. The digital or on / off functions inherent to binary valves require unique control algorithms for pressure control, detection of end-of-stroke, and occlusion of flow paths.

[0115] Controller 14035 controls valves N1 and LP1 according to several algorithms that can be executed sequentially or simultaneously based on received signals from pressure sensor or transducer 196. These control algorithms are specific to binary valves due to their inherent digital or on / off functions. The control algorithms include an algorithm for controlling the fluid flow rate through the pump, an algorithm for controlling the pressure within the working chamber 14020, an algorithm for detecting the end-of-stroke (EOS) condition, an algorithm for detecting a complete occlusion of the inlet line, an algorithm for detecting a complete occlusion of the outlet line, an algorithm for detecting a partial occlusion, and an algorithm for measuring an access metric (an indicator of the quality of blood flow obtained from the patient's vein or fistula access).

[0116] Controller 14035 calculates information regarding the flow of liquid through the pump based on the pressure signal from sensor 196 when valves N1, LP1 are closed. Controller 14035 uses the received pressure data to control the working chamber pressure, detect EOS, occlusion, partial occlusion, and determine the access metric.

[0117] Explanation of pressure control The flow rate through a diaphragm pump actuated by air pressure, such as the pod pump 23a, is controlled by setting the target pressure of the working chamber 14020. Next, the pod controller 14035 controls the valves N1, LP1 that fluidly connect the pressure source to the working chamber of the pump, thereby controlling the pressure within the working chamber 14020 measured by the pressure sensor 196 fluidly connected to the working chamber 14020. In an exemplary control algorithm, the controller averages the pressure data from the pressure sensor 196 while the binary valves N1, LP1 are closed, and when the cumulative average pressure approaches or equals the target pressure, the valves N1, LP1 are opened. In one example, the controller 14035 closes the valves N1, LP1 when the magnitude of the pressure data is greater than or equal to the target pressure. In one example, the controller 14035 closes the valves N1, LP1 when the magnitude of the pressure data is greater than or equal to the value obtained by subtracting a predetermined constant value from the target pressure. In another example, the predetermined value is not constant and varies depending on the direction of travel and the duration or stage of the travel. In another example, the controller 14035 integrates the magnitude difference between the measured pressure and the target pressure, and when the integrated difference approaches or equals zero, the valves N1, LP1 are opened.

[0118] The flow of fluid through the pump is controlled by the magnitude of the negative pressure applied to the working chamber to fill the pumping chamber with liquid and the magnitude of the positive pressure applied to the working chamber to deliver the liquid from the pumping chamber. In some examples, the pod pump controller 14035 is programmed to receive or calculate the desired flow rate and / or maximum displacement volume of the pod pump 23a. The controller 14035 may set an initial target pressure for the filling and delivery strokes. The controller controls the pressure within the working chamber to reach or approach the target pressure. The controller monitors the time until the stroke is completed and determines the actual flow rate by dividing the displacement volume by the time to complete the stroke. The controller 14035 may change the target pressure based on the difference between the latest actual flow rate and the desired flow rate. For example, the controller 14035 may increase the target pressure if the measured actual flow rate is below the desired flow rate. In another example, if the measured actual flow rate exceeds the desired flow rate, the controller may reduce the target pressure. The controller 14035 may change the delivery stroke independently of the filling stroke. In one example, the controller 14035 may use a feedback loop that changes the delivery target pressure based on the flow rate measured during the delivery stroke to achieve the desired flow rate. In another example, the feedback loop changes the negative filling target pressure based on the flow rate measured during the filling stroke to achieve the desired filling rate.

[0119] In prior disclosures, a chamber connected to a pressure source by a binary valve was controlled based on limits regarding a target pressure. The controller connects the pressure source to the chamber by opening the valve between them when the magnitude of the measured pressure in the chamber is a predetermined amount lower than the magnitude of the target pressure. Next, when the magnitude of the measured pressure in the chamber reaches a second predetermined value that exceeds the magnitude of the target pressure, the controller closes the valve. In some cases, applying this limiting approach to a pneumatic diaphragm pump results in a magnitude of average chamber pressure that is less than the magnitude of the target pressure. In some cases, when the valve is opened, the magnitude of the pressure in the chamber increases very rapidly, but the decrease in the magnitude of the pressure due to the liquid flowing in and out of the pumping chamber is much slower. This discrepancy in the rate of pressure change biases the magnitude of the time-averaged pressure lower than the magnitude of the target pressure. When the flow of liquid in and out of the pump changes over time, the offset between the average pressure and the target pressure also changes over time, making it difficult to continuously correct the discrepancy in the rate of pressure change.

[0120] The pressure in the working chamber can be controlled by comparing the measured pressure with the target pressure. The controller opens and closes a pneumatic valve that connects the working chamber to a pressure source or a reservoir. The controller can open and close valve LP1 during the delivery stroke to maintain the pressure in working chamber 14030 near delivery target pressure 14052. Controller 14035 opens and closes valve N1 during the filling stroke to maintain the pressure in working chamber 14030 near filling 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 working chamber approaches or equals the target pressure.

[0121] In the algorithms shown in FIGS. 63 and 64, referring to FIG. 62, as described below, the controller 14035 controls valves N1 and LP1 to maintain the average pressure in the working chamber at the target pressure by maintaining the average pressure in the working chamber at the target pressure while valves N1 and LP1 are closed. Here, referring to the pressure control algorithm 14100 in FIG. 63 and also referring to FIG. 60, the pump controller (separate from or distinguishable from the controller 14035 in FIG. 60) selects the stroke direction 14105 and the target pressure, filling and PTF (pressure - target - filling), or delivery and PTD (pressure - target - delivery). When the filling stroke is selected, at 14110, the controller 14035 opens the valve that fluid - connects the NEG pressure source or the reservoir to the working chamber 14020 and monitors the pressure sensor 196 at 14120. At each time step in block 14130, the controller evaluates whether the magnitude of the pressure is greater than the magnitude of the target pressure, and if not, leaves the valve open. In block 14140, when the magnitude of the measured pressure becomes equal to or greater than the target pressure, the N1 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 criterion is met, transfers the controller logic to stroke end 14200. Note that the logic in block 14160 can be placed anywhere between 14140 and 14180 in the flowchart or can be a separate function 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. If the sum of the pressure differences is zero or less, the controller logic sets the sum of the pressure differences to zero in block 14180 and returns the logic to block 14110 where the N1 valve is opened.

[0122] A single controller can adjust the timing of the pump stroke, the setting of the target pressure, and the operation of the pneumatic control valve. Alternatively, the tasks can also be divided among two or more controllers. For example, the main controller determines the timing of the pump stroke and the target pressure, and the sub-controller controls the pneumatic control valve. Referring to FIGS. 63 and 60, when the main controller selects the delivery stroke, the main controller also specifies the target pressure, and the sub-controller transfers the logic to block 14210 (FIG. 63), and the LP1 valve is opened. In a series of steps similar to the filling process, the pressure in the working chamber 14020 is monitored by the pressure sensor 196 in block 14220. Block 14230 evaluates the pressure against the target pressure and, if the measured pressure is above the target pressure, transfers the logic to block 14240 where the LP1 valve is closed. Referring now to FIG. 60, after being instructed to close the LP1 valve at 14051, the chamber pressure 14055 continues to increase and the chamber pressure exceeds the target pressure. The chamber pressure 14055 can increase to 14052 due to the delay in valve closure and due to the fluid / thermodynamics that can affect the chamber pressure.

[0123] Referring to FIG. 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 this 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 the region 14080 in FIG. 62. Region 14085 is 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 FIG. 63, in block 14260 the EOS algorithm is executed and if EOS is detected, the stroke ends at 14200.

[0124] In block 14270, the total pressure difference from block 14250 is evaluated. If the total pressure difference in block 14270 is zero or less, the logic transfers to 14210 where the LP1 valve is opened again. Before the logic reaches block 14210, the total pressure difference is set to zero in block 14280, and at that point, LP1 is opened. Alternatively, the total pressure difference may be set to zero at any time in the logic after block 14270 and before block 14240.

[0125] Referring now to FIG. 62, the criterion for block 14270 can be graphically represented as an instance where the area of 14080 is equal to the area of 14085. The criterion for block 14270 is met when the sum of the actual pressure 14055 minus the target pressure 14050 (when the actual pressure is greater than the target pressure) is equal to the sum of the target pressure 14050 minus the chamber pressure 14055 (when the chamber pressure is also smaller). Alternatively, the criterion for 14270 is met when the sum of [the magnitude of the average pressure minus the magnitude of the target pressure] is zero or less.

[0126] In one example, in blocks 14130 and 14230, the chamber pressure P is compared to predetermined pressures PD, PF that differ only by a pressure offset from the target pressures PTD, PTF. In some examples, the magnitudes of PD, PF are predetermined values that are smaller than the magnitudes of the target pressures PTD, PTF in order to limit pressure overshoot. Referring now to FIG. 62, when PD is less than the target pressure (14050D), the signal to valve LP1 in FIG. 60 is sent earlier, and the peak pressure at 14052 is lower. In one example, since the average pressure for the filling stroke and the ejection stroke is different, the magnitude of the pressure offset is different for the filling stroke and the ejection stroke.

[0127] The delay in valve operation is a fixed value, and since the pressure overshoot is inversely proportional to the volume of the working chamber (which changes during the stroke), the overshoot also changes, as can be observed in Figure 61. Generally, the overshoot is maximum at the start of the delivery stroke 14060 and at the end of the filling stroke 14075 when the volume of the working chamber 14020 has the minimum volume. The offsets for the filling and delivery strokes may change during the stroke. In one example, the magnitude of the offset is maximum at the start of the delivery stroke and decreases in each charge cycle until the offset reaches its minimum value. In the same or another example, the magnitude of the offset is minimum at the start of the filling stroke and increases in each charge cycle until the offset reaches its maximum value. The offset value can vary depending on time, the number of charge cycles, valve openings, or the sum of the differential pressures when the valve is closed during the stroke.

[0128] Another example of the pressure control algorithm 14300 is shown in Figure 64. The algorithm 14300 is similar to the algorithm 14100 except for elements 14350, 14370, 14380, 14450, 14470 and 14480, and the difference between the measured pressure and the target pressure has been replaced by the average pressure. In blocks 14350 and 14450, the measured values of the pressure sensor 196 are averaged while the valves N1, LP1 are closed. In blocks 14370 and 14470, when the average pressure, PAVG, is equal to the target pressure within some predetermined margin, the logic sets the average pressure to zero and then transfers to blocks 14110, 14210 respectively to open the valves N1, LP1.

[0129] Detection of end of stroke An accurate or reliable determination of the flow velocity and flow rate through pump 23a, as shown in FIG. 60, depends on an accurate or reliable algorithm for determining the end of stroke (EOS). The end of stroke occurs when diaphragm 14025 moves across the cavity of the pump body and reaches one of the walls of the pump body. Controller 14035 detects the state of the chamber with respect to the wall by observing that the magnitude of the chamber pressure measured by pressure sensor 196 does not decrease when valves N1, LP1 are closed. Since diaphragm 14025 cannot move into contact with the wall of the chamber and thus cannot change the volume of working chamber 14020, the chamber pressure does not decrease.

[0130] The EOS detection algorithm detects the end of stroke state based on the valve state, the chamber pressure, and the rate of change of the chamber pressure. This algorithm detects the EOS state for a pneumatically driven diaphragm pump. In this case, the pneumatic pressure is controlled by a pneumatic valve connecting the pump to the pressure reservoir, a pressure sensor measuring the pneumatic pressure applied to the pump, and a controller communicating with the pump and the pneumatic valve. In one example, EOS detection is based on the number of charge cycles performed by the pneumatic valve and the rate of pressure change while the pneumatic valve is closed. In another example, EOS is declared when a predetermined number of charge cycles have occurred and the rate of change of the magnitude of the pressure is less than a predetermined rate. In another example, EOS detection is declared when a predetermined number of charge cycles have occurred, the pressure is within a predetermined range, and the rate of change of the magnitude of the pressure is less than a predetermined rate.

[0131] Referring now to FIG. 60, after the controller 14035 detects the end of the stroke (EOS), it changes the stroke direction from delivery to filling, or from filling to delivery. The end-of-stroke algorithm is schematically shown in FIG. 65 and can be understood with reference to FIG. 61. The EOS algorithm 14300 is executed in blocks 14160 and 14260 as part of the pressure control algorithm 14100, or the EOS algorithm can be executed in parallel. Block 14310 monitors the pressure in the working chamber as sensed by the pressure sensor 196 (FIG. 60). In block 14320, the number of charge cycles that occurred during the current stroke is compared to a predetermined number. If more than the predetermined number of charge cycles have occurred, in block 14330, the minimum rate of change of the magnitude of the pressure (dP / dt) is compared to a predetermined rate (dPEOS). If the minimum rate of change is less than the predetermined rate, in block 14340, the difference between the current pressure P and the target pressure PT is evaluated. If the difference is less than a predetermined difference DP, EOS is declared and the controller changes the pump stroke, the target pressure, and switches the state of the hydraulic valves 192, 193 (the valves in the dialysis system described herein can be diaphragm valves that are supplied by a manifold and actuated by the pressure controlled by the controller). If the difference between the chamber pressure and the target pressure is greater than the predetermined difference, the controller 14035 declares an occlusion.

[0132] Continuing to refer to FIG. 65, in block 14330, dP / dt is the minimum rate of change of the magnitude of the pressure in the working chamber. In some examples, the minimum rate of change is determined only while the pneumatic valves N1, LP1 are closed. In some examples, the minimum rate of change of the magnitude of the pressure is derived from low-pass filtering of the pressure values. In another example, the rate of change of the magnitude of the pressure itself is low-pass filtered before being compared to the predetermined rate of change of pressure (dPEOS).

[0133] Occlusion detection Referring now to FIG. 60, the controller 14035 can be configured to detect blockages in the flow into and out of the pump 23a. The user interface can notify, as an alert or alarm, that the intake line or the outlet line is blocked. In one example, the user can be instructed to inspect the blood lines 203 and 204 for kinks, compressions, or other blocking elements. The blockage detection algorithm can be considered a safety feature to prevent thrombosis in the blood circuit, or can also identify problems with the flow of fluid within the water circuit or the dialysate circuit.

[0134] Blockages in the pump inlet and outlet lines are detected by the controller 14035 based on information received from the pressure sensor 196, while the working chamber 14020 is isolated from the pressure reservoirs NEG, LPOS. The pressure sensor 196 measures the pressure within the working chamber. The controller 14035 detects blockages in the inlet line during the filling stroke and in the outlet line during the delivery stroke. The controller 14035 sums the pressure changes that occur within the working chamber while the valves N1, LP1 are closed. The controller 14035 determines the presence of a blockage by comparing the sum of the pressure changes over all charge cycles during a single pump stroke to the sum of the pressure differences during the previous stroke and a predetermined value. The controller 14035 can also perform blockage detection based on the number of charge cycles completed before the end of the stroke is detected, and / or based on the difference between the working chamber pressure and the target pressure.

[0135] Referring now to FIG. 66, the occlusion algorithm 14400 is shown as a flowchart starting at step 14410, where either a filling stroke or a delivery stroke starts by setting a target pressure and then opening valves N1, LP1 (FIG. 60) at step 14415. Valves N1, LP1 are closed at step 14420. At 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 a plurality of charge cycles 14427. In one example, the controller 14035 determines the pressure change from the previous time step to the current time step. During each time step that the pneumatic valves N1, LP1 are closed, Pi - 1 - Pi is calculated and this pressure change is added to the current sum of the pressure changes. In one example, the controller determines the pressure change from when the valves N1, LP1 are closed until they are opened again, and then adds this pressure change to the sum of the pressure changes (dPSUM) including all pressure changes since the stroke started at step 14410.

[0136] Continuing to refer to FIG. 66, after updating the sum of the pressure changes (dPSUM) at step 14425, the occlusion algorithm 14400 checks the end - of - stroke condition at step 14430. If EOS is not detected, the controller 14035 checks at step 14435 to see if the charge cycle is complete and whether it is time to open the valves again. The end - of - charge - cycle step 14435 can be 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 value of the pressure difference between the target pressure and the chamber pressure during the current charge cycle. If step 14435 determines that the charge cycle is not complete, the sum of the pressure changes is updated for the next time step at step 14435. When the charge cycle is complete, the pneumatic valves N1, LP1 are opened again at step 14415.

[0137] When it is determined in step 14430 that the stroke is completed, the occlusion algorithm 14400 proceeds to a plurality of independent occlusion tests in steps 14440, 14450, 14455, 14460. Step 14440 transfers the logic to the less sensitive step 14450 and the more sensitive step 14445. In one example, step 14440 selects low sensitivity for the short strokes or partial strokes of the blood pump due to the variability of the short strokes within the blood pump. In a short stroke, the diaphragm is not driven to contact the inner wall of the pod pump. Instead, the delivery stroke is shortened. In some medical applications, the short delivery stroke may be beneficial in reducing damage to blood cells between the diaphragm 14025 and the wall of the pod pump 23a. The short strokes have greater variability, and to avoid false occlusion detection, a less sensitive occlusion test in step 14450 may be recommended. In one example, for all non-short stroke operations, step 14440 transfers the logic to step 14445.

[0138] Continuing to refer to FIG. 66, the occlusion algorithm 14400, in step 14445, compares the sum of the pressure differences (dPSUM) during the just-completed stroke to the sum of the pressure differences (dPGOOD) for the last good stroke in the same direction. In one example, occlusion is detected when two consecutive strokes in the same direction have a dPSUM that is less than 30% of the last good stroke (dPsum). More generally, occlusion is detected when one stroke has a dPSUM that is less than a predetermined percentage of the last good stroke (dPsum). In one example, occlusion is detected when three or more strokes have a dPSUM that is less than a predetermined percentage of the last good stroke (dPsum). When occlusion is detected, the logic proceeds to step 14470, where an occlusion alert or alarm is sent to the user interface (UI), and in one example, the pump may be stopped. In some embodiments, the UI indicates which pump and where the inlet or outlet line is occluded. If occlusion is not detected in 14445, the logic proceeds to step 14455.

[0139] Figure 66 shows an overview in which the occlusion algorithm 14400 includes a comparison of the total pressure difference (dPSUM) during the just-completed stroke at the low-sensitivity step 14450 with the total pressure difference (dPGOOD) for the last good stroke in the same direction. In one example, occlusion is detected when three consecutive strokes in the same direction have a dPSUM that is less than 10% of the last good stroke (dPsum). In one example, occlusion is detected when one stroke has a dPSUM that is less than a second predetermined percentage of the last good stroke (dPsum). Alternatively, occlusion is detected when four or more strokes have a dPSUM that is less than a predetermined percentage of the last good stroke (dPsum). When occlusion is detected, the logic proceeds to step 14470, where an occlusion alert or alarm is sent to the user interface (UI), and in one example, the pump is stopped. In one embodiment, the UI indicates which pump and where the inlet or outlet line is occluded. If no occlusion is detected at 14450, the logic proceeds to step 14455.

[0140] In step 14455, the controller 14035 detects an occlusion if either of the following conditions occurs: during one or more consecutive strokes in the same direction, the number of charge cycles is less than a predetermined number, or the total pressure change (dPsum) is less than a predetermined limit (dPsum_limit). In one example, an occlusion is detected if either condition occurs during three consecutive strokes in the same direction. In another example, an occlusion is detected if either condition occurs in two consecutive cycles. In another example, the predetermined number of charge cycles is 5. In another example, the predetermined number of charge cycles is half the number of charge cycles in a typical stroke. When an occlusion is detected, the logic proceeds to step 14470, where an occlusion alert or alarm is sent to the user interface (UI). In one exemplary response, the pump is stopped. The controller may send data to the UI indicating which pump is affected and whether the occlusion occurred in the inlet line or the outlet line. If no occlusion is detected in 14455, the logic proceeds to step 14460.

[0141] In step 14460, the controller 14035 detects an occlusion if the magnitude of the pressure in the working chamber 14020 is significantly greater than the target pressure over a predetermined period. In one example, step 14460 detects an occlusion if the magnitude of the pressure in the working chamber 14040 is greater than the magnitude of the target pressure by more than 60 mmHg over a predetermined period. In another example, the predetermined period in step 14460 is 25% of the stroke duration, where the stroke duration is the time from the start of the stroke to the detection of EOS.

[0142] Detection of partial occlusion Partial occlusion can limit flow rate but does not impede flow in the liquid line. Depending on whether partial or complete occlusion is detected, the function of the hemodialysis device can be changed and / or the message to the user can be changed. The controller detects partial occlusion based on the flow rate of the most recent run and the run target pressure of that most recent run. The pump controller changes the target pressure to achieve the desired flow rate and increases the target pressure for the next run if the flow rate of the last run is below the desired flow rate. A given pump has a maximum target pressure, which can be a function of the pressure of the pressure reservoir and / or the usage of the given pump. In one example, if the target pressure for the most recent run is set to the maximum value and the most recent flow rate through the pump does not reach the desired flow rate, a partial occlusion can be declared. In another example, a partial occlusion can be declared if the flow rate of the most recent run is less than 75% of the desired flow rate, even though the target pressure for the most recent run is set to the maximum value. In a hemodialysis system, the partial occlusion detection function can be applied to the blood pump to determine whether there is a problem with an individual's vascular access or the arrangement of a set of blood lines.

[0143] Blood Flow Metrics In one embodiment, the controller can be programmed to provide an indicator of blood flow metrics (the quality or rate of blood flow from a venous access or arteriovenous fistula) to a user outside the body or of a hemodialysis system during the course of the filling stroke of each pump. For example, a flow metric value that provides the user with a continuous indicator of the quality or adequacy of blood flow in the blood line during treatment can be transmitted to a graphical user interface. The user interface (e.g., an electronic tablet, etc.) can provide the user with raw flow metric data. In another embodiment, the flow metric can be scaled proportionally in the range from 1 to 5, where the value "5" represents, for example, excellent flow, the value "3" represents marginal flow, and the value "1" represents occluded flow. Thus, mapping flow metric values in a specified range to each of the set values from "1" to "5" can simplify the user's interpretation of the adequacy of blood flow in the blood line. In other embodiments, the flow metric can be graphically displayed to the user, such as, for example, a moving bar graph or an expanding bar graph, a dial gauge, or a set of colored lights.

[0144] In a preferred embodiment, the controller may issue an alert to the user for a critical flow metric or a sub-optimal flow metric, such that the user can attempt to improve the blood flow within the blood line (e.g., reposition the line, straighten the line, adjust the vascular access cannula, etc.). The controller may be programmed to initiate a procedure to temporarily stop or stop the dialysate pump, including sending a signal to the user to provide sufficient time for the user to correct the condition before temporarily stopping or stopping the dialysate pump. Since an alert can be issued to the user regarding a low flow condition during the filling stroke, timely adjustment by the user can restore the flow metric to an acceptable value before the filling stroke is completed. Alternatively, the controller may be programmed to allow a sub-optimal flow metric value for two or three (or more) consecutive filling strokes before instructing the dialysate pump to stop. Thus, timely correction of the low flow condition by the user can avoid interruption of the dialysate pump operation and, in some cases, avoid interruption of the treatment. In one example, the controller is programmed to temporarily stop or stop the dialysate pump if the flow metric remains below 150 (e.g., dP / dt in mmHg / sec) during three consecutive filling strokes, and not to restart the dialysate pump until the flow metric exceeds 200 during five consecutive blood pumping strokes. In some of these embodiments, the controller enables the blood pump to continue operating while the dialysate pump is stopped, such that the user has an opportunity to restore a blood flow condition that enables the dialysate pump to be restarted, thereby avoiding early termination of the treatment.

[0145] Referring now to FIGS. 60 and 62, the controller 14035 can determine the flow metric during the filling stroke based on the pressure in the working chamber while the pneumatic valve N1 is closed. The pressure in the working chamber is measured by the pressure sensor 196 that communicates with the controller 14035. In one example, the controller 14035 can determine the flow metric based on the 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 the minimum rate of change of the working pressure during the stroke while the valve N1 is closed (i.e., the lowest or nearly lowest rate of pressure change detected by the controller). In another example, the controller 14035 can determine the flow metric based on the minimum rate of change of the working pressure during the stroke, excluding the charge cycle that generated the stroke end signal. In one example, the rate of change of the working pressure is determined during each charge cycle using a low-pass filter, and the minimum value of the rate of change for each charge cycle is low-pass filtered over the stroke to determine the flow metric.

[0146] Figure 67 shows the flowmetric algorithm 14500 as a flowchart starting with the "start of the filling process" using a blood pump (23a in Figure 60). The upstream valve 192 is opened and the downstream valve 193 is closed. The filling process continues by opening the pneumatic valve N1 at step 14515 and closing the valve N1 at step 14520 to generate a desired negative pressure or a pressure less than the ambient pressure in the working chamber 14020 of the blood pump 23a. The negative pressure in the working chamber 14020 draws blood from the access site through the tube 203 into the pumping chamber of the blood pump 23a. The magnitude of the negative pressure in the working chamber 14020 decreases as the filling pump chamber expands and compresses the gas in the working chamber 14020. This decrease in the magnitude of the negative pressure is sensed by the pressure sensor 196 and notified to the controller 14035 at step 14525 (Figure 67). The controller analyzes the data and (optionally) uses a low-pass filter (LPF) function to determine the rate of change of pressure (dP / dt) in the working chamber at step 14530. If the end of the charge cycle has occurred, step 14535 transfers the logic to step 14540 where the end of the process (EOS) is determined. If the end of the charge cycle has not occurred, the logic transfers to 14525 where the pressure signal is continuously monitored. If EOS is not detected at step 14540, the controller determines, at step 14545, the minimum magnitude of dP / dt while the valve N1 is closed. Next, the minimum or lowest dP / dt of the current charge cycle detected by the controller is used by the LPF to update the minimum dP / dt for the filling process at step 14550, and the valve N1 is opened again at step 14515 to start the next charge cycle. If EOS is detected at step 14540, the logic transfers to step 14555 where the pod controller 14035 reports the minimum dP / dt to the controller, and the controller converts the minimum dP / dt value into a more easily understandable indicator that is displayed on the user interface (UI).The UI can be a graphical display unit such as a tablet computer. The indicator is flowmetric of the intake blood line and access. In one example, the minimum dP / dt value is displayed as a value from 1 to 5, where 1 is an occluded access, 3 is a marginal access, and 5 is a freely flowing access. Here, access means a system of a needle or cannula, the placement of the needle or cannula, and the restriction of flow at the inlet to the needle or cannula. In one example, the flowmetric is 1 for a minimum dP / dt of less than 25 mmHg / s or is occluded, the flowmetric is 2 for a minimum dP / dt of 25 - 50 mmHg / s or is inadequate, the flowmetric is 3 for a minimum dP / dt of 50 - 75 mmHg / s or is marginal, the flowmetric is 4 for a minimum dP / dt of 75 - 100 mmHg / s or is good, and the flowmetric is 5 or excellent for a minimum dP / dt of 100 - 125 mmHg / s. In addition to displaying the flowmetric on the UI in step 14555, the flowmetric algorithm 14500 in step 14560 evaluates the flowmetric and issues an alert to the user 14570 if the flowmetric remains below a predetermined value for a predetermined number of strokes or period. In one example, step 14560 issues an alert in step 14570 if three consecutive filling strokes have a dP / dt that is below the value of 50 mmHg / second. In this case, regardless of the flowmetric or minimum dP / dt, the logic proceeds to the delivery stroke of the blood pump in step 14580 and then returns to initiate the filling stroke in step 14510.

[0147] Interaction with water purification device A hemodialysis device or apparatus (HDD) can be configured to interact and communicate with a water purification device (WPD) that mixes dialysate and supplies water to the HDD system to sterilize the HDD before and after a dialysis treatment. In conventional disclosures (see, e.g., U.S. Patent Application Publication No. 2016 / 0058933), a series of messages and data can be exchanged between the HDD controller and the WPD controller. In a more streamlined approach, the types of interactions between the two devices can be restricted and instead rely on pre-programmed or autonomous functions of the WPD. In one example, the WPD can be a vapor compression / distillation device. Alternatively or additionally, other water purification devices and methods such as semi-permeable membrane filtration, reverse osmosis, ultraviolet irradiation, charcoal adsorption, or any combination thereof can be used.

[0148] The HDD controller can be configured to send a start signal to the WPD that represents a command to initiate production of room temperature water, and the WPD proceeds according to an independently programmed processor. This is a mode typically used when feeding purified water to the HDD for mixing of dialysate and treatment. The HDD controller can also send a hot water start command to the WPD that represents a command to initiate production of hot water according to a pre-programmed process of the WPD. This is a mode typically used to perform the sterilization procedure of the WPD. The line connecting the WPD and the HDD (the water supply line of the HDD) and the HDD itself can be sterilized using processes programmed into one or more HDD controllers.

[0149] The HDD controller can also instruct the WPD to enter either the standby mode or standby state, or the idle mode or idle state. In the water vapor compression / distillation apparatus, the idle state may include the temporary stoppage of pumps or compressors, the turning off of heaters, the closing of valves, and the deactivation of control loops and water level controllers. In the standby mode or standby state, the WPD can generate purified water relatively quickly. Optionally, in the steam / distillation system, this may include heating the water to a point where the purified water system can be filled with water and the generation of purified water can be started, controlling the vent valve to maintain a low-pressure steam temperature target, and optionally generating enough water to fill the reservoir or alternatively draining the excess water generated. If the WPD starts from an inactive (off) state or idle state, the HDD controller can optionally be programmed to send commands early enough to enable the WPD to produce water by the time the HDD is expected to receive water supply (in some cases, this can be about 2 hours from a cold start or start from idle mode, or only about 10 minutes from standby mode). In most cases, the HDD controller instructs the idle WPD to enter the standby mode when the two systems establish communication or when restarted after turning off the power of one or both systems. This cannot occur if the error state is flagged.

[0150] During water supply, the HDD controller can send a stop signal to the WPD to instruct the WPD to enter the standby state. In this case, the standby state is an autonomous function of the WPD that maintains the generation of water or purified water sufficiently active so that water can be supplied based on instructions from the HDD within a relatively short time (e.g., within about 10 minutes after a start command or resume command is sent from the HDD to the WPD). Among other processes, this may include filling the purified water system with water and heating the water to a point where the generation of purified water can be quickly started.

[0151] The HDD controller can also send a sterilization start command to the WPD, which is usually scheduled to occur after the end of dialysis treatment or during the time between treatment sessions with the HDD. In this case, the WPD enters the automatic hot water generation mode. In a typical sequence, the HDD first instructs the WPD to transition to the water generation mode, and then, upon being notified that the WPD has entered the water generation mode, instructs the transition to the sterilization mode. When the water generated by the WPD reaches a predetermined temperature (e.g., 90 degrees C), a signal is transmitted to the HDD controller, and the HDD starts the sterilization procedure for the inlet line. The inlet line includes the flow path within the HDD before the branch point connects to the drain of the HDD or the flow path to the mixing circuit of the HDD (beyond this branch point, the internal flow path of the HDD can be sterilized by circulating hot water or chemical sterilant programmed without a "closed end"). In this state, all tubes connecting the output port or output line of the WPD to the input port or input line of the HDD are also sterilized.

[0152] The controller of the HDD can be programmed to sterilize the WPD-HDD connection line and the flow path at a predetermined minimum temperature for a predetermined minimum time. For example, the sterilization temperature can be set to 85 degrees C for a minimum time of 35 minutes. The temperature can be measured by a temperature sensor disposed in the water inlet line of the HDD. To reduce the number of temperature sensors within the HDD system, the inlet water temperature sensor can preferably also be disposed at a position within the HDD flow path that can monitor the temperature of the sterilant circulating through the HDD flow path during sterilization of the HDD system. Depending on the travel distance of the water flowing in before reaching the temperature sensor, the minimum sterilization temperature can be optionally adjusted taking into account the heat loss of the water before it reaches the sensor.

[0153] FIG. 68 shows a schematic diagram of a fluid flow path related to the hemodialysis system described in the previous application. Section A represents the blood flow path of the system, section B represents the dialysate balance adjustment and dialyzer delivery section, section C represents the section for storing, heating, and ultrafiltrating the dialysate, and section D represents the water inlet and dialysate mixing section. The water inlet line 400 is configured to connect to a water source from the outside. In this embodiment, the water source includes a water purification device (WPD) such as a steam compression / distillation device. For ease of reference, in this specification, the water inlet line 400 means the entire water line connection between the purified water outlet of the WPD and the point 402 where the HDD water inlet line has a valve connection to the internal flow path of the HDD. In practice, this inter-device water line may include one or more connectors or valves. However, for the purpose of sterilization, the water inlet line 400 can be regarded as including the entire inter-device water line.

[0154] The internal fluid flow paths of the WPD and the illustrated HDD can be configured to achieve a thorough and complete sterilization process, but special attention is required for the sterilization of the water inlet line connecting the WPD to the HDD and / or the inter-device lines. The water inlet line 400 has a valve connection 402 to the internal flow path of the HDD, and it should be noted that this inter-device fluid connection (WPD outlet line and HDD inlet line) is closed-ended for the purpose of thorough sterilization either chemically or thermally. This state is also reflected in the outlet line of the WPD. The HDD dialysate heater can be used to heat the water pumped in the reverse direction by one or more dialysate pumps to the HDD inlet line, the WPD outlet line, and the drain connection of the WPD. However, it may be more efficient that purified hot water (or water containing an appropriate chemical sterilant) is generated by the WPD and sent to the HDD in the normal forward direction, and the sterilizing liquid is discharged to the drain line 404 of the HDD.

[0155] Figure 69 shows a separated view of the portion of section D of the flow path of the HDD system. The temperature sensor can be arranged on line 400 and functions only to monitor the temperature of the incoming water. For the purpose of sterilization, the incoming heated water can be sent directly to drain 404, but this flow path depends on the operation of the water pump arranged within the WPD. On the other hand, the temperature sensor 406 can be arranged on the internal line 408 connected to the water pump 410, which can provide the pumping action necessary to move water through lines 400 and 408. This sensor can also be used to monitor the temperature of the liquid during sterilization of various internal flow paths within the HDD system. The heated liquid from section C in Figure 68 can be sent to the flow path within section D via the water line 408. The inlet line sterilization flow path incorporating the water pump 410 within the system shown in Figure 69 (also refer to Figure 68) is guided through the conductivity / temperature sensors 412, 414 within the dialysate mixing path, and then bypasses the dialysate tank 416 by closing valve 418 and opening valve 420, thereby being led to the drain line 404. In an alternative embodiment, it should also be noted that the monitoring of the temperature of the sterilizing liquid can be carried out using the existing temperature sensors (i.e., sensor 412 or sensor 414) already installed for the purpose of mixing the dialysate without adding a temperature sensor to the water inlet line 400 or 408. In all these cases, either an actively managed valve or a passive check valve ensures that the sterilizing liquid is led to the drain line 404.

[0156] In one embodiment, as shown in FIG. 70, the start of the sterilization procedure may initially include the HDD command 450 causing the WPD to initiate normal water production. Subsequently, the HDD starts priming the flow path with water from the WPD (452). Next, the HDD instructs the WPD to produce water heated to the required sterilization temperature (454). Optionally, the temperature at which the WPD produces the heated water is higher than the minimum sterilization temperature specified for the line interconnecting the WPD and the HDD. This is because it takes into account the heat loss of the water as it passes through the interconnecting line. For example, if the minimum sterilization temperature is 85 degrees C, the WPD can be programmed to produce water at 90 degrees C at its outlet. Optionally, the HDD can be programmed to initiate its own heated water production using an internal heater (e.g., heater 411 shown in FIG. 68) (456). This helps to prepare the HDD to perform its own sterilization after the device - to - device line 400 has been sterilized and to maintain a high ambient temperature within the HDD housing to limit heat loss during the sterilization of the device - to - device line 400. When both the HDD and the WPD have heated their respective fluid flow paths to a predetermined temperature, the HDD controller can instruct the WPD to start supplying the heated water from the product outlet line to the device - to - device line (inlet line 400) connecting the WPD to the HDD (458).

[0157] The water sterilization temperature can vary during the sterilization period. Optionally, the controller of the HDD can be programmed to track the time during which the measured temperature reaches or exceeds the minimum sterilization temperature programmed into the controller.

[0158] As shown in FIG. 71, optionally, before starting the sterilization counter for the inter-device line 400, the HDD controller starts controlling the HDD internal pump and the associated valves to circulate the heated water flowing in from the WPD for a predetermined period to completely fill the sterilization flow path with the hot water (460). In addition to the inter-device line, in one example, this flow path includes a flow path within the HDD that leads to the dialysate tank 416 but guides the sterilizing water through a line that is diverted to the drain 404 by one or more valves 418, 420 and through the water pump 410 in the mixing circuit (see, for example, FIG. 69). In one example, the HDD controller directs the heated water from the WPD to the HDD drain for about 2 minutes before the inter-device line sterilization counter is started.

[0159] The HDD controller may be programmed to include a predetermined minimum sterilization temperature (e.g., 78 degrees C). When this temperature is detected by a temperature sensor (e.g., sensor 406, or sensor 412 or 414), the controller starts the sterilization timer 462. When this minimum sterilization temperature is maintained for a predetermined minimum sterilization time (e.g., 35 minutes) (464), the controller may declare that the sterilization of the inter-device line 400 is complete. The sterilization timer is updated as long as the detected temperature is above the minimum sterilization temperature (464).

[0160] Optionally, the controller may be programmed to include a timer 466 that accumulates the time when the detected temperature is lower than the minimum sterilization temperature but above a predetermined low temperature threshold (e.g., 70 degrees C). When a predetermined low temperature timeout value is reached (e.g., 10 minutes for timing out the sterilization cycle), the controller may notify the user interface of an alarm and instruct the WPD to temporarily stop water generation (468). Optionally, the controller may also be programmed to notify an alarm and instruct the WPD to temporarily stop water generation (468) when the detected temperature is lower than a predetermined low temperature threshold (e.g., 70 degrees C).

[0161] If the sterilization of the inter-device line 400 is successful (470), the HDD controller can close the water inlet line valve 402, instruct the WPD to start the sterilization procedure, and start the HDD sterilization procedure. If the sterilization of the inter-device line 400 fails, the user is notified and the WPD is instructed to temporarily stop water production (468). Under these circumstances, the HDD controller can optionally start the re-priming procedure for its flow path and reset the sterilization timer to 472. Next, the HDD controller can wait for user input on whether to retry the sterilization procedure (474). If not retrying, the HDD can optionally initiate a service call (476). The controller can be configured to provide appropriate instructions to the user on the user interface or automatically send appropriate messages to a remote server and service center via an Internet communication link.

[0162] The HDD controller may instruct the WPD to enter a flush mode in which source water flows into the system and passes through the filters within the system. This is typically performed after filter replacement. If filter replacement (e.g., carbon filter) is indicated, the HDD controller first instructs the WPD to enter an idle state and subsequently issues an alert to the user on the graphical user interface that the WPD is ready for filter replacement. When the user indicates completion of this task, the HDD instructs the WPD to enter a standby state and subsequently executes the flush mode. The HDD can be instructed to return to the standby state upon completion of this task, enabling a rapid start of the water production state at the start of treatment. To ensure a more reliable indication of filter quality, the flush mode can also be instructed prior to fluid sampling. It may also be instructed when the WPD system has been in an idle or standby state for a predetermined period.

[0163] Status messages can be sent between the Water Layer of the HDD system controller architecture and the Therapy Layer of the HDD system controller architecture. Exemplary messages that the Water Layer can receive from the WPD can include the following.

[0164] - The current operating state of the WPD - The current identification code or identifier of the WPD - The date the WPD filter was installed - Whether the filter needs to be replaced - Whether communication with the WPD has been interrupted - Whether the WPD is indicating an operational error - Whether the WPD is indicating a fail-safe error - The time since the WPD was last sterilized - Whether the WPD needs to be sterilized - The software version installed on the WPD system controller Status messages regarding the operating state of the WPD can include one or more of the following.

[0165] - WPD active (independent of the HDD); upon initiation of the communication link between the HDD and the WPD, the HDD instructs the WPD to enter the standby state. - WPD at idle; the product valve is closed.

[0166] - WPD at standby; the product valve is open. - The WPD generates cold water; the product valve is open. - The WPD is waiting for a filter replacement; the product valve is closed.

[0167] - The WPD flushes the line and filter after filter replacement. - The WPD generates hot water; the product valve opens when the temperature is reached. - The WPD performs sterilization; the product valve is closed.

[0168] -WPD generates a water sample for testing (e.g., chloramine test); the product valve is closed. -WPD is waiting for user input in the GUI to send out the water sample for testing.

[0169] -WPD is in a failsafe state; the product valve is closed. Preferably, the HDD controller instructs the WPD to always maintain the standby mode when the WPD is not performing another process. If it is during another process (e.g., sterilization), the HDD controller waits for this process to complete. When the WPD enters the standby mode, the HDD controller may check whether the WPD should perform a filter flushing process. If it should, the WPD starts the filter flush process. Also, for example, if the power is cut off before the filter flush is completed after filter replacement, the HDD may instruct the filter flush process.

[0170] Optionally, before starting water generation for treatment, the HDD can be programmed to request the user to sample the generated water from the WPD for various contaminants such as chloramine. The HDD can instruct the WPD to start the water sampling state. When the WPD indicates that it is ready for sampling, the HDD issues an alert to the user to collect and test the water sample. If the user indicates that the sample has passed the test, the HDD can instruct the WPD to start water generation for treatment. If the user indicates that the sample has failed the test, the HDD can optionally instruct the WPD to enter the standby state.

[0171] Errors generated from the WPD during water generation can be notified to the HHD, and then the HHD can check the error status and send an instruction to issue an alert to the user via an interface (e.g., HDD interface). Next, the WPD controller waits for an instruction from the user on whether to resume water generation or transition to the standby state. The fail-safe error state usually stops the WPD operation and notifies the HDD to start the end-of-treatment procedure.

Claims

1. A fluid processing cassette, comprising: an intermediate plate disposed between a first plate and a second plate, the intermediate plate having a first side surface from which a plurality of passage walls protrude and a second side surface from which a plurality of passage walls protrude, the first plate being in contact with the passage walls on the first side surface of the intermediate plate, and the second plate being in contact with the passage walls on the second side surface of the intermediate plate, the intermediate plate; a plurality of end portions, each end portion being orthogonal to and coinciding with an outer end portion of the intermediate plate, the plurality of end portions; a pump station having a pump diaphragm and a pump operation chamber defined by the first side surface of the intermediate plate, the pump diaphragm being seated on the first side surface of the intermediate plate, the pump station; a pump operation passage defined by at least two of the plurality of passage walls on the first side surface of the intermediate plate, the pump operation passage fluidly connecting the pump operation chamber to a cassette pump operation port disposed at a first end portion of the plurality of end portions and located between the intermediate plate and the first plate, the fluid processing cassette comprising the pump operation passage.

2. The fluid processing cassette according to claim 1, wherein the plurality of passage walls on the second side surface of the intermediate plate define one or more fluid passages.

3. The fluid processing cassette according to claim 1, wherein the cassette pump operation port is a portion integrated with the intermediate plate.

4. The fluid processing cassette according to claim 2, wherein the pump station further comprises first and second pump ports fluidly connecting a pumping chamber to individual first and second fluid passages, the pumping chamber being defined by the pump diaphragm and the first side surface of the intermediate plate.

5. The fluid processing cassette according to claim 2, comprising a pump port in the pump station that fluidly connects the fluid passage on the second side surface of the intermediate plate to a pumping chamber defined by the pump diaphragm and the first side surface of the intermediate plate.

6. The fluid processing cassette according to claim 2, comprising an opening in the intermediate plate at the pump station, the opening enabling the pump diaphragm to move from the first plate to the second plate when actuated by a positive or negative pressure supplied through the pump operating passageway.

7. The fluid processing cassette according to claim 5, comprising a fluid passage on the second side surface of the intermediate plate that fluidly connects the pumping chamber to a cassette fluid port located at the first end of the cassette and between the intermediate plate and the second plate.

8. The fluid processing cassette according to claim 5, comprising a fluid passage on the second side surface of the intermediate plate that fluidly connects the pumping chamber to a cassette fluid port located at the second end of the cassette and between the intermediate plate and the second plate.

9. A fluid processing cassette, an intermediate plate disposed between a first plate and a second plate, the intermediate plate comprising a plurality of passage walls protruding from a first side surface and a plurality of passage walls protruding from a second side surface, the first plate contacting the passage walls on the first side surface of the intermediate plate, and the second plate contacting the passage walls on the second side surface of the intermediate plate; the intermediate plate; a plurality of end portions, each end portion being orthogonal to and coinciding with an outer end portion of the intermediate plate; the plurality of end portions; a valve station comprising a valve operating chamber defined by a valve diaphragm and the first side surface of the intermediate plate, the valve diaphragm being seated on the first side surface of the intermediate plate; the valve station; a valve operating passage defined by at least two of the plurality of passage walls on the first side surface of the intermediate plate, the valve operating passage fluidly connecting the valve operating chamber to a cassette valve operating port disposed at a first one of the plurality of end portions and located between the intermediate plate and the first plate; the valve operating passage; a fluid processing cassette comprising.

10. The fluid processing cassette according to claim 9, wherein the plurality of passage walls on the second side of the intermediate plate define one or more fluid passages.

11. The fluid processing cassette according to claim 10, wherein the valve station further comprises first and second valve fluid ports that fluidly connect individual first and second fluid passages on the second side of the intermediate plate to a valve fluid chamber defined by the valve diaphragm and the first side of the intermediate plate.

12. The fluid processing cassette according to claim 11, wherein one or both of the valve fluid ports include a raised valve seat for sealing the valve diaphragm on the first or second valve fluid port when positive pressure is applied to the valve diaphragm via the valve actuation passage.

13. The fluid processing cassette according to claim 11, wherein the first fluid passage is fluidly isolated from the second fluid passage except via the first and second valve fluid ports.

14. The fluid processing cassette according to claim 11, comprising a fluid passage disposed on the second side of the intermediate plate, the fluid passage fluidly connecting a valve fluid chamber defined by the valve diaphragm and the first side of the intermediate plate to a cassette fluid port located at the first end and between the intermediate plate and the second plate.

15. The fluid processing cassette according to claim 11, comprising a fluid passage disposed on the second side of the intermediate plate, the fluid passage fluidly connecting a valve fluid chamber defined by the valve diaphragm and the first side of the intermediate plate to a cassette fluid port located at a second end of the plurality of ends and between the intermediate plate and the second plate.

16. The fluid processing cassette according to claim 1, wherein the first plate is joined to the passage wall on the first side of the intermediate plate.

17. The fluid processing cassette according to claim 16, wherein the first plate is joined to the passage wall on the first side of the intermediate plate by ultrasonic welding.

18. The fluid processing cassette according to claim 1, wherein the first plate is laser welded to the passage wall on the first side of the intermediate plate.

19. The first plate and the second plate allow transmission of a laser wavelength, the intermediate plate is opaque, and the first plate and the second plate are laser welded to the intermediate plate. The fluid processing cassette according to claim 1.

20. A fluid processing cassette, An intermediate plate disposed between a first plate and a second plate, the intermediate plate including a fluid port and a passage wall, an axis of the fluid port being parallel to a surface of the cassette, the passage wall protruding from a first side surface, and a plurality of passage walls protruding from a second side surface, the first plate contacting the passage wall on the first side surface of the intermediate plate, and the second plate contacting the passage wall on the second side surface of the intermediate plate. The intermediate plate and, A plurality of end portions, each end portion being orthogonal to an outer end portion of the intermediate plate and coinciding with the outer end portion of the intermediate plate. The plurality of end portions, The fluid port is disposed at a first end of the cassette and is fluidly connected to a fluid passage defined by at least two passage walls. The fluid processing cassette.

21. The fluid processing cassette according to claim 20, wherein the intermediate plate is formed of an opaque material, and the first plate and the second plate are transparent or translucent.

22. The fluid processing cassette according to claim 20, wherein the first plate and the second plate allow transmission of a laser wavelength, and the intermediate plate is opaque.

23. The fluid processing cassette according to claim 20, wherein the first plate and the second plate are laser welded to the intermediate plate.

24. The fluid processing cassette according to claim 23, wherein the first and second plates are laser welded to the passage wall.

25. A fluid processing cassette, A first plate and, An intermediate plate disposed adjacent to the first plate, The intermediate plate including a peripheral wall protruding from a first side surface of the intermediate plate around a pump or a valve. The intermediate plate and, The first plate is in contact with the peripheral wall on the first side surface of the intermediate plate, The fluid processing cassette, wherein the intermediate plate is opaque, the first plate permits transmission of a laser wavelength, and the peripheral wall is laser welded to the first plate.

26. An operation port located at an end of the intermediate plate, wherein an axis of the operation port is parallel to a surface of the cassette, the operation port; A diaphragm located within the peripheral wall on the intermediate plate, wherein the diaphragm and the peripheral wall define an operation chamber together with the first plate, the diaphragm; An operation passage including a pair of passage walls extending from the peripheral wall to the operation port and fluidly connecting the operation port to the operation chamber, and further comprising; The fluid processing cassette according to claim 25, wherein the pair of passage walls are sealed to the first plate by laser welding.

27. Two fluid ports respectively defined by openings passing through the intermediate plate within the peripheral wall; A second plate; Two fluid passages respectively defined by passage walls protruding from a second side surface of the intermediate plate, wherein each fluid passage is in fluid communication with one of the fluid ports, the two fluid passages, and further comprising; The fluid processing cassette according to claim 25, wherein the second plate transmits a laser wavelength and is laser welded to the fluid passage.

28. An operation port located at an end of the intermediate plate, wherein an axis of the operation port is parallel to a surface of the cassette, the operation port; A diaphragm located within the peripheral wall on the intermediate plate, wherein the diaphragm and the peripheral wall define an operation chamber together with the first plate, the diaphragm; A pair of passage walls extending from the peripheral wall to the operation port and fluidly connecting the operation port to the operation chamber, and further comprising; The fluid processing cassette according to claim 25, wherein the pair of passage walls are sealed to the first plate by laser welding.

29. Two fluid ports respectively defined by openings passing through the intermediate plate within the peripheral wall; A second plate; Two fluid passages respectively defined by passage walls protruding from the second side surface of the intermediate plate, each fluid passage being in fluid communication with one of the fluid ports, and the two fluid passages. The fluid processing cassette according to claim 26, wherein the second plate transmits a laser wavelength and is laser welded to the fluid passage.

30. A fluid processing cassette assembly, An intermediate cassette disposed between a first outer cassette and a second outer cassette, each cassette having A first plate, A second plate, An intermediate plate disposed adjacent to the first plate, A peripheral wall protruding from the first side surface of the intermediate plate around the pump station or the valve station, and The intermediate cassette including the intermediate plate including a plurality of fluid passages protruding from the second side surface of the intermediate plate. A fluid processing pod disposed in the inter-cassette space between the intermediate cassette and the first or second outer cassette, the fluid processing pod having a fluid connection to a fluid passage in the intermediate cassette, the first or second outer cassette via a fluid conduit passing through the second plate of the intermediate cassette, the first or second outer cassette. The first plate is laser welded to the peripheral wall on the first side surface of the intermediate plate, and the second plate is laser welded to the passage wall on the second side surface of the intermediate plate. A fluid processing cassette assembly.

31. The fluid processing cassette assembly according to claim 30, wherein the intermediate plate is opaque and the first and second plates allow transmission of a laser wavelength.

32. The intermediate plate, An operating passage, and An operating port located at an end of the intermediate plate, the axis of the operating port being oriented parallel to the surface of the cassette that houses the intermediate plate, and the operating port. The fluid processing cassette assembly according to claim 30, wherein the operating port is fluidly connected to the pump station or the valve station via the operating passage.

33. A fluid processing cassette, An intermediate plate, An actuating port that is attached to the first end of the intermediate plate and extends beyond the first end, A peripheral wall surrounding a pump station or a valve station, the peripheral wall having a break portion, and the peripheral wall protruding from the first side surface of the intermediate plate, An actuating passage formed by two passage walls protruding from the first side surface of the intermediate plate, the actuating passage extending from the break portion of the peripheral wall to the actuating port, and the intermediate plate including the actuating passage, A diaphragm disposed within the peripheral wall on the intermediate plate, the diaphragm including a bead on the outer edge of the diaphragm, A first plate having a first side surface facing the intermediate plate, A first side surface that contacts the peripheral wall and the passage wall, A holding wall that protrudes from the first side surface by a distance sufficient to compress the bead against the intermediate plate, the holding wall being disposed to fit within the peripheral wall and sized, and the first plate including the holding wall, The first plate and the diaphragm define an actuating chamber, a fluid processing cassette.

34. The holding wall fits within the peripheral wall to form an annular gap, the annular gap is in fluid communication with the actuating passage, and the holding wall includes one or more perforations for providing a fluid path between the actuating chamber and the annular gap. The fluid processing cassette according to claim 33.

35. The fluid processing cassette according to claim 34, wherein the holding wall further includes a curved surface formed to support the diaphragm within the holding wall.

36. The fluid processing cassette according to claim 35, wherein the holding wall further includes a groove extending from one perforation across the diaphragm to the opposite side of the holding wall.

37. The fluid processing cassette according to claim 33, wherein the intermediate plate is formed of an opaque material and the first plate is transparent or translucent.

38. The fluid processing cassette according to claim 33, wherein the first plate permits transmission of a laser wavelength and the intermediate plate is opaque.

39. The fluid processing cassette according to claim 33, wherein the first plate is laser welded to the peripheral wall or the passage wall.

40. Further comprising a second plate, The intermediate plate is, Two fluid ports respectively defined by openings passing through the intermediate plate within the surrounding wall; Two fluid passages respectively defined by passage walls protruding from the second side surface of the intermediate plate, each fluid passage being in fluid communication with one of the fluid ports, the two fluid passages; and further comprising, The fluid processing cassette according to claim 33, wherein the second plate transmits a laser wavelength and is laser welded to the fluid passage.

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