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 relates generally to improvements in the design and construction of fluid pumping or mixing cassettes, cassette assemblies, their components, and related devices. [Background technology]

[0002] Fluid processing cassettes containing diaphragm pumps and / or valves can be fluidly actuated (either hydraulically or pneumatically). In some examples, the cassettes are 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 air pressure in a predetermined manner to the various pumps or valves of the cassette.

[0003] Some fluid processing cassettes may be substantially planar in shape, with a wide side adjacent to a thin or narrow side, the thin or narrow side having a thickness relatively less than the overall wide side dimension of the cassette. Liquid inlet and outlet ports may be incorporated into the end or thin side of the cassette. However, in many of these devices, the cassette's actuation ports are located on the face or wide side of the cassette directly above the actuation chamber of the pump or valve being controlled. This generally provides the shortest route for the actuation passage within the cassette from the external cassette actuation port to the actuation chamber and diaphragm of the pump or valve within the cassette. Furthermore, in many cases, the cassette's pumping or valve stations or regions (including either the actuation chamber on one side or the liquid transfer chamber on the opposing side) may be formed by spherical or hemispherical chamber walls that extend above the plane of the cassette face, which can make the overall cassette thicker than desired in some applications. In other cases, a pump module may include a set of sandwiched or stacked blocks with pneumatic or fluid passages embedded within one or more blocks. This configuration may also result in an overall device thickness greater than desired for a particular application. Some applications may require multiple fluid processing cassettes to be mounted adjacent to one another in a tight space. In these cases, it may be desirable to position many cassettes adjacent to one another, stacking them on top of one another, or at least positioning them closely with their wide sides facing one another. 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 a pump cassette to plug directly into its associated pressure distribution manifold (e.g., a manifold that selectively delivers air pressure to the pump cassette under the control of an electronic controller). In previously disclosed embodiments of hemodialysis systems using pneumatically actuated, self-contained pump cassettes, the pump cassette is connected to a corresponding pneumatic manifold via flexible tubing, which poses significant challenges during assembly and operation. When a pump cassette can be located in close proximity to its associated manifold, a direct plug-in connection between the two offers significant advantages. Under these circumstances, it would be particularly advantageous to have a compact manifold that allows a direct interface to the pump cassette, positioned so that the cassette or cassette assembly can be plugged into and unplugged from the manifold's actuation port with minimal effort.

[0005] The design and operation of pneumatic distribution manifolds also allows for the use of binary pressure control valves rather than continuously variable orifice valves, offering significant advantages in both cost and reliability. However, in this case, the control of pressure supply to individual cassette pumps or valves by the 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 period and duration of binary valve actuation to achieve precise 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 narrow side or end. The pump and / or valve cassette includes a middle plate disposed between two outer plates. A first outer plate faces a first side of the middle plate, and a second outer plate faces a second side opposite the middle plate. The first outer plate is spaced from the middle plate to form a first inter-plate space. The second outer plate is spaced from the middle plate to form a second inter-plate space. The thicknesses of the first and second outer plates are limited to a thickness sufficient to provide rigidity to the plates and to provide sealing surfaces against opposing passage walls on either side of the middle plate. In some embodiments, the thickness of each outer plate, together with the thickness of the middle plate therebetween, defines the overall thickness of the cassette. In other embodiments, liquid inlet and outlet ports protrude 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 pump or valve stations can determine the overall wide side dimensions of the cassette. The swept volume of an onboard pump is a function of the diameter of the pump station and its associated diaphragm and the depth of the diaphragm's range of motion, defined by the depth of the passage walls in the mid-plate, which in turn determines the thickness of the cassette and the dimensions of its wide side. For any given pump or valve station, the mid-plate includes an actuation side and an opposing liquid side, with the actuation side carrying the pump or valve diaphragm. Actuation passages within the cassette to individual pump or valve stations can be contained within the mid-plate passages of the first inter-plate space and extend generally parallel to the wide side of the cassette. Liquid passages within the cassette are contained within the mid-plate passages of the second inter-plate space and generally extend parallel to the wide side of the cassette, except in some cases where the liquid passages connect to the cassette's inlet or outlet.In this configuration, the first and second outer plates function primarily to provide a roof or restricting wall over the respective actuation and liquid transfer valve or pump areas.

[0007] In one embodiment, a fluid treatment cassette can include an intermediate plate disposed between a first plate and a second plate, the plate having a length, a width, and a plate thickness, with 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 a width of the first inter-plate space, and the second plate is spaced apart from the intermediate plate, defining a width of the second inter-plate space. The ends of the cassette have a cassette thickness defined by the thickness of each plate plus the widths of the first and second inter-plate spaces, and the faces of the cassette are defined by the length and width of the first or second plate. The intermediate plate can include a pump station formed by a pump diaphragm and a first side of the intermediate plate, the pump diaphragm seated against the first side of the intermediate plate and having a range of motion defined by the width of the first inter-plate space. The pump actuation passage extends parallel to the face of the cassette within the first inter-plate space, connecting a pump actuation chamber defined by the first plate and the pump diaphragm to a cassette pump actuation port disposed within the first inter-plate space at a first end of the cassette. First and second pump fluid ports within the pump station may fluidly connect the respective first and second fluid passages of the second inter-plate space to the pumping chamber formed by the pump diaphragm and the first side of the middle plate. The pump fluid port within the pump station may fluidly connect the fluid passages of the second inter-plate space to the pumping chamber formed by the pump diaphragm and the first side of the middle plate. Alternatively, an opening may be provided in the middle plate at the pump station, allowing the pump diaphragm to move from the first plate to the second plate when actuated by positive or negative pressure supplied through the pump actuation passage. The plates (first, middle, and second) have a thickness that is insufficient to allow fluid or actuation passages to travel through the plates in a direction parallel to the plane of the cassette.The fluid passage extends into the second inter-plate space and can be fluidly connected to a pumping chamber formed by the pump diaphragm and a first side of the intermediate plate, the connection being made via one or more pump fluid ports in the intermediate plate, the fluid passage extending parallel to the face of the cassette within the second inter-plate space, and the fluid passage connecting the pumping chamber to a cassette fluid port located at the first end or the second end of the cassette within the second inter-plate space.

[0008] In one embodiment, a fluid treatment cassette can include an intermediate plate disposed between a first plate and a second plate, the plate having a length, a width, and a plate thickness, with 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 a width of the first inter-plate space, and the second plate is spaced apart from the intermediate plate, defining a width of the second inter-plate space. The ends of the cassette have a cassette thickness defined by the thickness of each plate plus the widths of the first and second inter-plate spaces, and the faces of the cassette are defined by the length and width of the first or second plate. The intermediate plate can include a valve station formed by a valve diaphragm and a first side of the intermediate plate, the valve diaphragm seated against the first side of the intermediate plate and having a range of motion defined by the width of the first inter-plate space. The valve actuation passage extends parallel to the face of the cassette within the first inter-plate space, connecting a valve actuation chamber defined by the first plate and the valve diaphragm to a cassette valve actuation port disposed within the first inter-plate space at a first end of the cassette. First and second valve fluid ports within the valve station may fluidly connect respective first and second fluid passages in the second inter-plate space to the valve fluid chambers formed by the valve diaphragm and the first side of the middle plate. One or both 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 except through the first and second valve fluid ports.A fluid passage may extend into the second inter-plate space and fluidly connect to a valve fluid chamber formed by the valve diaphragm and a first side of the middle plate, the connection being made via two valve fluid ports in the middle plate, the fluid passage extending into the second inter-plate space parallel to the face of the cassette, and the fluid passage connecting the valve fluid chamber to a cassette fluid port located at a first end or a second end within the second inter-plate space.

[0009] In another embodiment, a fluid treatment cassette can include an intermediate plate disposed between a first plate and a second plate, the plate having a length, a width, and a plate thickness, with 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, which defines a width of the first inter-plate space, and the second plate is spaced apart from the intermediate plate, which defines a width of the second inter-plate space. The ends of the cassette have a cassette thickness defined by the thickness of each plate plus the widths of the first and second inter-plate spaces, and the faces of the cassette are defined by the length and width of the first or second plate. The intermediate plate can include a pump station formed by a pump diaphragm and a first side of the intermediate plate, the pump diaphragm seated against the first side of the intermediate plate and having a range of motion defined by the width of the first inter-plate space. The intermediate plate may include first and second valve stations, each formed by a valve diaphragm and a first side of the intermediate plate, the valve diaphragm seated against the first side of the intermediate plate and having a range of motion defined by the width of the first inter-plate space. A pump actuation passage for the pump station and a valve actuation passage for each of the first and second valve stations are provided. The pump actuation passage extends within the first inter-plate space parallel to the face of the cassette, connecting a pump actuation chamber defined by the first plate and the pump diaphragm to a cassette pump actuation port located within the first inter-plate space at a first end of the cassette. Each of the valve actuation passages extends within the first inter-plate space parallel to the face of the cassette, connecting a valve actuation chamber defined by the first plate and the valve diaphragm to a cassette valve actuation port located within the first inter-plate space at a first end of the cassette.Inlet and outlet valve fluid ports at each of the two valve stations may be provided, and one or more pump fluid ports at the pump station may be provided, each of the valve and pump fluid ports fluidly connecting a fluid passage in the second inter-plate space to a pumping chamber formed by the pump diaphragm and the first face of the middle plate, and a valve fluid chamber at each valve station formed by a corresponding valve diaphragm and the first face of the middle plate. The fluid passage has a flow path 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 is selectively actuated to allow unidirectional flow of fluid through the fluid passage. The fluid passages extend into the second inter-plate space and are fluidly connected to a pumping chamber formed by the pump diaphragm and the first side of the intermediate plate, the connection being made through a pump fluid port in the intermediate plate, and the fluid passages are fluidly connected to a valve fluid chamber of each valve station formed by a corresponding valve diaphragm and the first side of the intermediate plate, each connection being made through two valve fluid ports in the intermediate plate, such that the fluid passages extend within the second inter-plate space parallel to the face of the cassette, and the fluid passages connect the pumping chamber and each valve fluid chamber to cassette fluid inlet ports and cassette fluid outlet ports located at the first end or second end of the cassette within the second inter-plate space. The cassette fluid inlet port and the cassette fluid outlet port are positioned at a second end of the cassette, the cassette pump actuation port and the cassette valve actuation port are configured to plug directly into mating actuation receptacles outside the cassette, and the fluid inlet port and the fluid outlet port are positioned to be connected to a fluid source or fluid destination outside the cassette via flexible or malleable tubing.The fluid passages extend into the second inter-plate space and fluidly connect to the pumping chambers formed by the pump diaphragms and the first side of the middle plate via pump fluid ports in the middle plate, and the fluid passages are fluidly connected to the valve fluid chambers of each valve station, each valve fluid chamber being formed by a corresponding valve diaphragm and the first side of the middle plate via two valve fluid ports in the middle plate. The fluid passages extend parallel to the face of the cassette in the second inter-plate space and connect the pumping chambers and each valve fluid chamber to cassette fluid inlet and outlet ports, which emerge from the cassette via rigid conduits that pierce the face of the cassette, starting from the middle plate and passing through the first or second outer plate.

[0010] In further embodiments, multiple walls may be formed on first and second sides of the intermediate plate, the walls arranged to combine with the first and second plates within the cassette to form actuation or fluid passageways. A first type of wall may include parallel walls defining the actuation or fluid passageways, a second type of wall may include circumferential peripheral walls defining pump or valve actuation stations, and a third type of wall may include adjacent end walls defining passage terminations through which valve or pump fluid ports extend through the intermediate plate. The first plate may include one or more circumferential valve or pump diaphragm retainers configured to fit within the circumferential peripheral walls of the opposing intermediate plate defining the pump or valve actuation stations, the retainers arranged to clamp the peripheral bead or rim of an associated diaphragm disposed within the pump or valve station of the intermediate plate. The retainers may include holes, perforations, or slots to allow communication of actuation fluid or gas between the valve or pump actuation chambers enclosed by the retainer and the associated actuation passageways. The first plate includes elongated ribs configured to be positioned within the mating actuation passages of the middle plate, the cross-sectional size and length of the ribs being determined to adjust the volume of the actuation passages to a predetermined value between the actuation ports of the cassette and the associated valve or pump actuation chambers.

[0011] In another embodiment, a fluid treatment cassette can include an intermediate plate disposed between a first plate and a second plate, the plate 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 spaced apart from the intermediate plate defining a width of the first inter-plate space, and the second plate spaced apart from the intermediate plate defining a width of the second inter-plate space, the ends of the cassette having a cassette thickness defined by the thickness of each plate plus the widths of the first and second inter-plate spaces, and the faces of the cassette 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 defined by a first valve diaphragm and a first side surface of the intermediate plate, the second valve station being defined by a second valve diaphragm and a second side surface of the intermediate plate, the first valve diaphragm seated on the first side surface of the intermediate plate and having a range of motion defined by the width of the first inter-plate space, the second valve diaphragm seated on the second side surface of the intermediate plate and having a range of motion defined by the width of the second inter-plate space, a first valve actuation passage for the first valve station extending within the first inter-plate space parallel to the face of the cassette, and a second valve actuation passage for the second valve station extending within the second inter-plate space parallel to the face of the cassette. A first valve actuation passage connects a first valve actuation chamber bounded by the first plate and first valve diaphragm to a first cassette valve actuation port located at the first end of the cassette within the first inter-plate space, and a second valve actuation passage connects a second valve actuation chamber bounded by the second plate and second valve diaphragm to a second cassette valve actuation port located at the first end of the cassette within the second inter-plate space.

[0012] In another embodiment, a fluid treatment cassette can include an intermediate plate disposed between a first plate and a second plate, the plate having a length, a width, and a plate thickness, with 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 a width of the first inter-plate space, and the second plate is spaced apart from the intermediate plate, defining a width of the second inter-plate space. The ends of the cassette have a cassette thickness defined by the thickness of each plate plus the widths of the first and second inter-plate spaces, and the faces of the cassette are 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 a first pump diaphragm and a first side of the intermediate plate, the second pump station being formed by a second pump diaphragm and a second side of the intermediate plate, the first pump diaphragm seated on the first side of the intermediate plate and having a range of motion defined by the width of the first inter-plate space, and the second pump diaphragm seated on the second side of the intermediate plate and having a range of motion defined by the width of the second inter-plate space. A first pump actuation passage for the first pump station extends parallel to the face of the cassette within the first inter-plate space, and a second pump actuation passage for the second pump station extends parallel to the face of the cassette within the second inter-plate space, the first pump actuation passage connecting a first pump actuation chamber defined by the first plate and first pump diaphragm with a first cassette pump actuation port located at the first end of the cassette within the first inter-plate space, and the second pump actuation passage connecting a second pump actuation chamber defined by the second plate and second pump diaphragm with a second cassette pump actuation port located at the first end of the cassette within the second inter-plate space.

[0013] 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 outer cassette, the intermediate plate having a length, a width, and a plate thickness, with 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, which defines a width of a first inter-plate space, and the second plate is spaced apart from the intermediate plate, which defines a width of a second inter-plate space. The ends of the cassette have a cassette thickness defined by the thickness of each plate plus the widths of the first and second inter-plate spaces, 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, each including a valve or pump actuation chamber, are connected to actuation passages that extend parallel to the face of the cassette within the first or second inter-plate space and terminate in individual cassette valve or pump actuation ports at a first end of the cassette between the first or second inter-plate spaces. Fluid processing pods are disposed in the inter-cassette spaces between the middle cassette and the first or second cassette, and the pods have fluid connections to the fluid passages in the middle, first, or second cassette via fluid conduits that penetrate the face of the middle, first, or second cassette. The first ends of the middle, first, and second cassettes are disposed on a first side of the cassette assembly such that the cassette valve or pump actuation ports are configured to be inserted into or removed from an actuation port-receptacle assembly facing the first side of the cassette assembly. The fluid processing pod may include a diaphragm pump pod having actuation and fluid connections to actuation passages and fluid passages in the intermediate, first, or second cassette via actuation conduits and fluid conduits that penetrate the faces of the intermediate, first, or second cassette. The actuation conduits of the diaphragm pump pod connect to actuation passages in the first or second interplate spaces of the intermediate, first, or second cassette and have a continuous connection to a cassette actuation port for the diaphragm pump pod at a first end of the intermediate, first, or second cassette.The fluid conduits of the diaphragm pump pods may connect with fluid passages in the first or second inter-plate spaces of the intermediate, first, or second cassettes and with diaphragm valves within the cassettes, and the actuation passages of the diaphragm valves may connect with cassette actuation ports for the diaphragm valves at the first ends of the intermediate, first, or second cassettes. The fluid conduits in any of these configurations may be rigid. Multiple 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 multiple fluid processing pods may be rigid to provide structural support for the cassette assembly. The cassette assembly frame may be configured to increase the structural rigidity of the cassette assembly, and the cassette assembly frame may include a rigid support plate on a second side of the cassette assembly opposite the first side of the cassette assembly, the support plate configured to engage with a cassette loading device 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 outer cassette, the intermediate plate having a length, a width, and a plate thickness, with 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, which defines a width of a first inter-plate space, and the second plate is spaced apart from the intermediate plate, which defines a width of a second inter-plate space. The ends of the cassette have a cassette thickness defined by the thickness of each plate plus the widths of the first and second inter-plate spaces, and the faces of the cassette are defined by the length and width of the first or second plate. The plurality of diaphragm valves or pumps may include valve or pump actuation chambers connected to actuation passageways that extend parallel to the faces of the cassettes within the first or second inter-plate spaces and terminate in individual cassette valve or pump actuation ports at a first end of the cassette between the first or second inter-plate spaces. A first fluid processing pod may be disposed in the inter-cassette space between the middle cassette and the first or second cassette. The fluid processing pod has fluid connection to the fluid passageways within the middle, first, or second cassette via fluid conduits that extend through the faces of the middle, first, or second cassette. The second fluid processing pod may include a diaphragm pump pod that has actuation and fluid connection to the actuation passageways and fluid passageways within the middle, first, or second cassette via actuation conduits and fluid conduits that extend through the faces of the middle, first, or second cassette. The first ends of the intermediate, first, and second cassettes are positioned on a first side of the cassette assembly such that the cassette valve or pump actuation ports are configured to be inserted into or withdrawn from actuation port receptacle assemblies that face the first side of the cassette assembly.The actuation conduits of the diaphragm pump pods may connect to actuation passages in the first or second inter-plate spaces of the intermediate, first, or second cassettes and have 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 conduits of the diaphragm pump pods may connect to fluid passages in the first or second inter-plate spaces of the intermediate, first, or second cassettes and to diaphragm valves within the cassettes, and the diaphragm actuation passages may connect to cassette actuation ports for the diaphragm valves at the first end of the intermediate, first, or second cassettes. The fluid conduits may be rigid. Multiple fluid processing pods may be provided between the intermediate cassette and the first cassette, and between the intermediate cassette and the second cassette, and the associated fluid conduits of the multiple fluid processing pods may be rigid to provide structural support for the cassette assembly. The cassette assembly frame can be configured to increase the structural rigidity of the cassette assembly, the cassette assembly frame including a rigid support plate on a second side of the cassette assembly opposite the first side of the cassette assembly, the support plate configured to engage with a cassette loading device opposite the actuation port receptacle.

[0015] In another aspect of the invention, a 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 actuation output ports of the manifold and an opposite second side including a second set of transfer ports configured to connect to the actuation input ports of the cassette assembly. The first set of transfer ports includes a first spatial array configured to match the spatial array of the actuation output ports of the manifold. The second set of transfer ports includes a second spatial array configured to match the spatial array of the actuation input ports of the cassette assembly, the first spatial array of transfer ports being different from the second spatial array of transfer ports. The first spatial array can cover an area having a first length and a first width on the first side of the adapter housing, and the second spatial array covers an area having a second length and a second width on the second side of the adapter housing. The second length is greater than the first length so that the manifold adapter housing overhangs the side of the manifold. The second side of the housing can include an elastomeric wiper gasket consisting of a plurality of wiper seals, each associated with a transfer port on the second side of the adapter housing. The wiper gasket can be recessed under the top plate of the adapter housing.

[0016] In another aspect, a seating device is described for 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 linkages on a first side of the cassette mount and an opposite second side of the cassette mount. The linkages on the first side of the cassette mount are connected to a first fixed flange of the fixed frame member, and the linkages on the second side of the cassette mount are connected to a second fixed flange of the fixed frame member. Each of the plurality of linkages may include a swing arm having a first end pivotally coupled to the fixed flange and a second end coupled to an elongated slot in the cassette mount. The second end of the swing arm is configured to move in an arcuate path to move the cassette mount, such that the elongated slot limits movement of the cassette mount by the swing arm to linear motion 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 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 generally parallel to the direction of movement of the cassette mount, an elongated slot formed in the movable flange and oriented perpendicular to the direction of movement of the cassette mount, and the first and second rails configured to retain a mounting side of the cassette. The handle assembly is pivotally connected to the cassette mount such that movement of a handle of the handle assembly away from the fixed frame member moves the cassette mount away from the fixed frame member, and movement of the handle toward the fixed frame member moves the cassette mount toward the fixed frame member.The pivot connections of the handle assembly may include a first pivot connection to the first fixed flange of the first handle arm, a second pivot connection to the second fixed flange of the second handle arm, a third pivot connection to the handle swing arm connected to the first movable flange of the cassette mount of the first handle arm, and a fourth pivot connection to the handle swing arm connected to the second movable flange of the cassette mount of the second handle arm. The first and third pivot connections and the second and fourth pivot 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 approximately 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 to lock the cassette mount in a retracted position when the handle of the handle assembly is moved toward the fixed frame member. [Brief explanation of the drawings]

[0017] Non-limiting embodiments of the present invention will now 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 drawings, each identical or nearly identical component shown will typically be represented by a single numeral. For clarity, not every component will be labeled in every drawing, and not every component of each embodiment of the present invention will be shown unless illustration is necessary to enable those skilled in the art to understand the invention. [Figure 1A-1B] 1A-1C are schematic cross-sectional views of an embodiment of a pump cassette during a fill stroke and a pump stroke. [Figure 2A-2B] 10A-10C are schematic cross-sectional views of another embodiment of a pump cassette during a fill stroke and a pump stroke. [Figure 3A-3B] 1 is a schematic cross-sectional view of an exemplary diaphragm valve in operation. [Figure 4A-4B] 10 is a schematic cross-sectional view of another embodiment of a pump cassette in operation. [Figure 5A-5B]10 is a schematic cross-sectional view of an optional additional feature of an exemplary pump cassette in operation. [Figure 6] FIG. 1 is a perspective view of an exemplary pump or valve cassette. [Figure 7] FIG. 7 is a front perspective view of the pump or valve cassette shown in FIG. [Figure 8] FIG. 8 is a perspective view of the inside of the outer plate of the exemplary cassette shown in FIGS. 6 and 7. [Figure 9] FIG. 9 is a perspective view of the actuation side of the midplate of the exemplary cassette shown in FIGS. 6, 7 and 8. [Figure 10] FIG. 10 is an enlarged view of the pump station and valve station on the actuation side of the intermediate plate shown in FIG. 9. [Figure 11] FIG. 10 is a perspective view of the flow path side of the midplate of an exemplary pump or valve cassette. [Figure 12] FIG. 10 is a perspective view of another embodiment of a pump or valve cassette. [Figure 13] FIG. 13 is a perspective view of a first side of the midplate of the exemplary cassette illustrated in FIG. 12; [Figure 14] FIG. 14 is a perspective view of a second side of the intermediate plate shown in FIG. 13. [Figure 15] FIG. 10 is a rear perspective view of the cassette assembly; [Figure 16] FIG. 16 is a front perspective view of the cassette assembly shown in FIG. 15; [Figure 17A] 11A and 11B are front and rear perspective views of another embodiment of a cassette assembly; [Figure 17B] 11A and 11B are front and rear perspective views of another embodiment of a cassette assembly; [Figure 18] FIG. 1 is an exploded view of an exemplary conventional cassette assembly. [Figure 19] FIG. 19 is a side view of the assembled cassette assembly of FIG. 18 showing the pneumatic actuation lines and associated connectors of the assembly. [Figure 20] FIG. 10 is a perspective view of another embodiment of a cassette assembly secured to a frame assembly; [Figure 21] FIG. 21 is an exploded view of the frame assembly shown in FIG. 20. [Figure 22A] 1A-1C are front and rear perspective views of a top plate of an exemplary frame assembly. [Figure 22B] 1A-1C are front and rear perspective views of a top plate of an exemplary frame assembly. [Figure 23] FIG. 1 is a front perspective view of a hemodialysis machine. [Figure 24] FIG. 24 is a front perspective view of the housing of the hemodialysis machine shown in FIG. 23. [Figure 25] FIG. 25 is a rear perspective view of the housing shown in FIG. 24. [Figure 26] FIG. 1 is a schematic diagram of an exemplary pressure distribution manifold. [Figure 27] FIG. 1 is a schematic diagram of an exemplary pressure distribution manifold. [Figure 28] FIG. 1 is a schematic diagram of an exemplary pressure distribution manifold. [Figure 29] FIG. 1 is a schematic diagram of an exemplary pressure distribution manifold. [Figure 30] FIG. 25 is a perspective view of the top of the housing of FIG. 24 enclosing the cassette assembly separated from the corresponding manifold assembly. [Figure 31] FIG. 31 is a perspective view of the top of the housing as shown in FIG. 30 with the cassette assembly connected to a corresponding manifold assembly. [Figure 32] FIG. 1 is a rear perspective view of an exemplary pressure distribution manifold and associated interface adapter. [Figure 33] FIG. 33 is an exploded view of the pressure distribution manifold shown in FIG. 32. [Figure 34] FIG. 1 is a perspective view of an exemplary pressure distribution manifold and associated sensor substrate. [Figure 35] FIG. 35 is a perspective view of the lower block of the pressure distribution manifold shown in FIG. 34. [Figure 36] 35A and 35B are bottom and top perspective views of the upper block of the pressure distribution manifold shown in FIG. 34. [Figure 37] 35A and 35B are bottom and top perspective views of the upper block of the pressure distribution manifold shown in FIG. 34. [Figure 38] FIG. 1 is a flow path schematic of an arrangement of pneumatic passages within an exemplary pressure distribution manifold. [Figure 39] FIG. 2 is a perspective view of an exemplary pneumatic passageway within a pressure distribution manifold. [Figure 40] FIG. 40 is a perspective view of the exemplary pneumatic passage arrangement shown in FIG. 39 within the pressure distribution manifold. [Figure 41] FIG. 1 is a flow path schematic of an arrangement of pneumatic passages within an exemplary pressure distribution manifold. [Figure 42] FIG. 10 is a perspective view of another exemplary pneumatic passageway within a pressure distribution manifold. [Figure 43] FIG. 43 is a perspective view of the exemplary pneumatic passage arrangement shown in FIG. 42 within the pressure distribution manifold. [Figure 44] FIG. 1 is a rear perspective view of the hemodialysis machine housing showing the placement of the pressure distribution manifold. [Figure 45] FIG. 1 is a front perspective view of a hemodialysis machine housing showing installation of an exemplary manifold adapter. [Figure 46] FIG. 10 is a front left perspective view of an exemplary cassette assembly positioned on top of a housing and aligned with a manifold adapter. [Figure 47] FIG. 1 is a perspective view of an exemplary pneumatic distribution manifold positioned below a housing cutout for a manifold adapter. [Figure 48] FIG. 1 is a rear perspective view of a hemodialysis machine housing showing installation of an exemplary pressure distribution device and interface adapter. [Figure 49] FIG. 1 is a front perspective view of a hemodialysis machine housing showing installation of an exemplary interface adapter. [Figure 50] FIG. 1 is a partial cutaway view of a housing of a hemodialysis machine showing an exemplary cassette loading assembly mounted to the ceiling of the housing. [Figure 51] FIG. 1 is a perspective view of an exemplary manifold adapter rail. [Figure 52] FIG. 1 is a partially exploded top perspective view of an exemplary manifold adapter positioned on a pressure distribution manifold. [Figure 53] FIG. 53 is a partial exploded view of the manifold adapter of FIG. 52 from below. [Figure 54] FIG. 10 is a plan view of an exemplary wiper gasket of the manifold adapter. [Figure 55] FIG. 55 is a cross-sectional view showing a cross section of the wiper gasket of FIG. 54. [Figure 56] FIG. 1 is a bottom perspective view of an exemplary cassette loading assembly with the operating handle in a raised (released) position. [Figure 57] FIG. 1 is a front perspective view of an exemplary cassette loading assembly with the operating handle in a lowered (engaged) position. [Figure 58] FIG. 58 is a bottom perspective view of the exemplary cassette loading assembly of FIG. 57 with the operating handle lowered. [Figure 59] FIG. 59 is a rear perspective view of the exemplary cassette loading assembly of FIGS. 57 and 58 with the operating handle lowered. [Figure 60] FIG. 1 is a schematic diagram of fluid flow paths within a hemodialysis machine. [Figure 61] 1 is a graphical representation of pressure fluctuations in the working chamber of a pump in a hemodialysis machine. [Figure 62] 1 is a graphical representation of pressure fluctuations in the working chamber of a pump in a hemodialysis machine. [Figure 63] 1 is an exemplary flow chart of an algorithm for controlling the pressure in the actuation chamber of a pneumatically actuated pump. [Figure 64] 10 is an exemplary flow chart of an alternative pressure control algorithm for a pneumatically actuated pump. [Figure 65] 1 is an exemplary flow chart for an exemplary pneumatically actuated pump end-of-stroke detection algorithm. [Figure 66]1 is an exemplary flowchart of an occlusion detection algorithm for a fluid path in a diaphragm-based pump system. [Figure 67] 10 is an exemplary flow chart of an algorithm for determining resistance to flow during a pumping fill stroke. [Figure 68] 1 is a schematic diagram of fluid flow paths in an exemplary hemodialysis system. [Figure 69] FIG. 69 is a schematic diagram of an isolated view of a section of the fluid flow path of the hemodialysis system shown in FIG. 68. [Figure 70] FIG. 1 is a state diagram illustrating a disinfection procedure for a hemodialysis system. [Figure 71] FIG. 1 is a state diagram illustrating temperature control before and during a sterilization procedure. DETAILED DESCRIPTION OF THE INVENTION

[0018] Cassette with liquid and air passages in a plane In some pumping applications, it is advantageous to locate the actuation ports of a hydraulically or pneumatically actuated pump or valve cassette on the end, thin, or narrow side of the cassette rather than on the wider side of the cassette. This allows the cassette to be inserted into a receptacle containing an array of actuation ports associated with a pressure supply manifold on the narrow side rather than the wider side. This may maximize the functions that the pump / valve cassette can perform within a limited space. In some situations, overall space constraints may make it advantageous to minimize the overall thickness of the cassette. This can be achieved by making the cassette thicker than the excursion of the sealing diaphragm. Ideally, each outer plate of the cassette functions primarily as a roof or end wall of the pump or valve actuation or liquid delivery chamber or passageway, and its thickness is insufficient to completely enclose any liquid or actuation passageway that extends generally parallel to the face or wider side of the cassette. The actuation passages are configured to extend within the space between the middle plate and the outer plate (e.g., the first outer plate) of the cassette, within an inter-plate space that defines the maximum range of motion of one or more diaphragms of the cassette. The width of the inter-plate space (and therefore the maximum range of motion of the flexible membranes or diaphragms) can be predetermined by the height of the passage walls formed on the actuation side and / or the liquid-transporting side of the cassette middle plate. The height of the passage walls on one side of the middle plate can be different from the height of the passage walls on the opposite side of the middle plate. For example, to accommodate a desired fluid flow rate, the passage walls on the liquid side of the middle plate can be taller to provide a larger cross-sectional area of ​​the liquid-transporting passages, while the cross-sectional requirements of the actuation passages (and therefore the passage wall height) on the actuation side of the middle plate can be smaller.

[0019] 1A and 1B show cross-sectional schematic diagrams of cassette 10 near the end of the fill stroke and the end of the pumping stroke, respectively. Middle plate 12 is disposed between first outer plate 14 and second outer plate 16. Flexible diaphragm 18 is disposed within first interplate space 20, with fluid flow paths residing within second interplate space 22. To reduce the thickness of the pump and / or valve cassette, any actuation passages preferably extend within first interplate space 20, which is the space defined by the depth, or linear extent E, of the diaphragm's travel between middle plate 12 and first outer plate 14. For an onboard diaphragm pump, its stroke volume is a function of the depth, or linear extent E, of the diaphragm's travel between diaphragm 18 and the effective surface area the diaphragm occupies on the broad side of the cassette. The depth of the diaphragm's preferred range of motion E may also depend on how effectively the diaphragm's displacement volume can be increased by increasing its effective surface area. In this embodiment, two pump chamber liquid ports 24a, 24b, representing an inlet and an outlet, are shown, each connected to a separate fluid passage within the interplate space 22, which are schematically separated by a wall 38 (the direction of liquid flow shown is arbitrary and depends on which liquid line is opened or closed by a downstream valve during the diaphragm's filling or pumping stroke). In another embodiment, as shown in FIGS. 2A and 2B, a single pump chamber liquid port 24c (or two or more such ports) can be used, with the pump chamber liquid port 24c alternating between an inlet port and an outlet port depending on which downstream valve is opened or closed in the single liquid line within the interplate space 22. When the volume of the actuation chamber 26 is at its minimum, the corresponding pump chamber 28 is at its maximum (filling stroke, see FIGS. 1A, 2A). When the volume of the working chamber 26 is at a maximum, the volume of the corresponding pump chamber 28 is at a minimum (delivery stroke, see FIGS. 1B, 2B).Once the depth E of the diaphragm range of motion on the cassette is selected, the thickness T of the cassette can be reduced by avoiding locating the actuation ports directly above the diaphragms to be actuated (as in prior art designs). This is accomplished by locating the actuation ports on the thin or narrow side of the cassette and extending the actuation passages to the individual diaphragms within a first inter-plate space 20 within the cassette 10. This space is defined by a middle plate 12 on which the diaphragms 18 seat and a first outer plate 14, which provides a cover or roof for an actuation chamber 26 for each diaphragm 18. Surrounding the periphery of each diaphragm is a wall 30 that spans the inter-plate space 20 and, together with the outer plate 14, completes each actuation chamber 26, except for an actuation port or window 32 that connects the actuation chamber 26 to its corresponding actuation passage (represented by an arrow in the first inter-plate space 20). The actuation passages extend within the interplate space 20 to the outer circumferential edge or narrow side of the cassette, where they terminate as cassette actuation ports (see, e.g., FIG. 9 ). Note that the actuation passages can be less deep than provided by the interplate space 20, depending on the specified excursion depth E for the diaphragm 18. To minimize the overall thickness T of the cassette 10 for a given specified diaphragm excursion depth E, the nominal thickness P of each plate 12, 14, 16 can be minimized (within structural rigidity constraints and any constraints imposed in achieving adequate welding or bonding of the outer plates to the middle plate passage walls). Depending on fluid flow rate requirements, the cassette thickness can also be minimized by reducing the depth of the liquid flow passages (i.e., the height of the passage walls) within the second interplate space 22.

[0020] The overall thickness T of the cassette depends on the amount of depth required by the liquid flow paths or passages on the opposing sides of the middle plate 12 of the cassette 10 within the second inter-plate space 22. In the pumps shown in Figures 1A-2B and the valves shown in Figures 3A-3B, the required depth of the liquid passages determines the depth of the second inter-plate space 22. Depending on the liquid flow rate specified for the cassette, the second inter-plate space 22 may have a depth L that is substantially less 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 passageways: a first passageway terminating at valve port 34a in the middle plate 12, and a second passageway terminating at valve port 34b in the middle plate 12. (In some embodiments, multiple liquid passageways can terminate at separate valve ports in the middle plate of a single valve station.) As shown in FIGS. 3A and 3B, the depth of the range of motion, E, for a diaphragm valve, is determined by the degree of relaxation required to allow the diaphragm 18 to lift away from the fluid ports 34a, b that it is designed to block. The valve diaphragm 36 can move away from ports 34a, b under negative actuation pressure, as shown in FIG. 3A, to allow liquid flow, or move to block ports 34a, b under positive actuation pressure, as shown in FIG. 2B, to block liquid flow. The separate liquid passageways within the cassette valve station are represented schematically by the walls 38 shown within the second interplate space 12. In the illustrated example, the valve ports 34a, b may optionally include raised elements 40 (distributed circumferentially around the valve ports) to improve the diaphragm's sealing efficiency. Such raised elements may only need to be present around one of the valve ports to be effective. Thus, when the valve diaphragm relaxes or pulls away from the valve's liquid port, liquid is allowed to flow from one liquid passage through its associated port into the liquid valve chamber and then out through the liquid port of the second liquid passage connected to that valve station. The selection of the liquid passage cross-sectional area may depend on the desired liquid flow resistance and the desired holdup volume or dead space occupied by the liquid passage within the cassette. The desired liquid passage cross-sectional area determines the depth (or passage wall height) of the liquid passage occupying the second inter-plate space 22 between the middle plate 12 and the second outer plate 16 of the cassette. The liquid passages and actuation passages may be formed from the middle plate or individual outer plates, or may be formed independently of the outer or middle plates.In a preferred configuration, the middle plate is molded, 3D printed, or otherwise cast with the desired passage walls on either side of the middle plate, thereby simplifying the construction of the outer plates. The outer plate 14 may include the roof or diaphragm limiting wall of the actuation chamber 26, and the outer plate 16 may include the roof or liquid passages within the cassette. In this manner, the inter-plate space between the middle and outer plates may be further reduced.

[0022] Thus, as shown in FIG. 1A, in a preferred embodiment, the thickness T of the pump or valve cassette 10 can be determined by the nominal thickness P of each of the middle and two outer plates plus the depth E of the diaphragm 18 and the depth L of the liquid passage formed by the second inter-plate space 22 provided on the cassette. To maximize the efficiency of positioning and distributing the valve and pump stations on the middle plate 12, it may be advantageous to arrange several working passages and chambers on both sides of a single middle plate 12. In this case, the thickness T of the cassette is determined by the depth of the largest diaphragm's working range on each side of the middle plate. For example, if the depth E of the pump diaphragm's working range is the same on each side of the middle plate 12, the thickness T of the cassette is equal to (2 x E) + (3 x P).

[0023] 4A and 4B show an alternative embodiment of a diaphragm pump in a pump cassette 50. In this case, the pump chamber fluid ports are replaced with wide openings 42 through which the diaphragm 44 can pass as it moves from the fill position (FIG. 4A) to the pumping position (FIG. 4B). The overall thickness T' of this cassette is therefore determined by the total travel distance or length E' of the diaphragm 44 plus the thickness P of the two outer plates 46, 48. The pump diaphragm 44 substantially utilizes the entire 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 sealing wall 54 covered by the second outer plate 48. While liquid inlet / outlet pump ports 56, 58 are shown in this embodiment, other embodiments may include only a single port that functions as both an inlet and an outlet, or may include multiple ports where the inlet or outlet function is determined by downstream valves in the liquid passages associated with each pump port. This configuration minimizes the overall thickness of the cassette because the swept volume created by the diaphragm is essentially doubled without the intermediate plate, allowing the distance between the plates to be substantially reduced for any desired pump swept volume.

[0024] 5A and 5B illustrate additional features that may optionally be included in the pump or valve cassette. In this case, the diaphragms 60, 62 are shown secured to the 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 the diaphragms 60, 62 may be secured to the intermediate plate 12 by adhesive, by heat welding, by overmolding a section of the intermediate plate and clamping it around the bead, by applying a solid continuous ring in place against the diaphragm bead, or by any number of other methods that ensure the diaphragm is secured 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 actuation chamber 26. In the illustrated example, the retainer or retaining wall 68, 100 is located inside the peripheral wall 30 of the actuation chamber 26. As shown in cross section, the depicted portion of the retaining wall 68 displays two perforations, slots, windows, or holes 70 that allow actuation pressure (e.g., air pressure) to be transmitted to the actuation side of the diaphragm 60. For most of its circumference, the retainer or retaining wall 68 extends uninterruptedly from the inside of the first outer plate 14 or 46 to a position adjacent the bead 64, 66 of the diaphragm 60, 62. If the bead is made of an elastomeric material, the retainer or retaining wall 68, 100 acts to partially compress the bead during cassette assembly when the first outer plate is attached to the opposing middle plate. The tight fit helps ensure that the diaphragm is securely attached and an airtight / watertight seal is formed. In a preferred configuration, two or more retaining wall perforations 70 (or holes) can be distributed around the periphery of the retaining wall 68, thereby allowing positive or negative actuation pressure to be transmitted simultaneously to multiple sections of the diaphragm 60, 62 relative to one another.

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

[0026] In the illustrated example, the diameter of the retainer or retaining wall 68, 100 is small enough to allow a gap 72 to exist between the retainer or retaining wall 68, 100 and the peripheral wall 30 of the actuation chamber 26. The gap 72 allows the actuation pressure of the fluid or air to be distributed to the individual perforations 70 in the retaining wall 68. The retainer or retaining wall 68, 100 may be a separate element that is assembled with other components of the cassette, or the retainer or retaining wall 68, 100 may be formed or co-molded with either the middle plate 12 or the first outer plate 14 of the cassette.

[0027] 5A and 5B also show that the inner walls of the actuation or first outer plate 14 or 46 can optionally include curved buttresses 74 or 76 that help the inner walls of the actuation chamber 26 conform to the curvature of the diaphragms 60, 62 when the diaphragms 60, 62 are fully expanded toward the actuation-side first plate 14 or 46. This can help reduce stress on the more peripheral portions of the diaphragms 60, 62 when fully retracted within the actuation chamber 26. Similarly, as shown in FIG. 5B, curved buttresses 78 can be located along the end walls of the liquid pumping chamber 52 (liquid or second outer plate 48) for similar reasons. In these examples, shaping the inner walls of the outer plates 14, 46, and 48 does not require an increase in the overall thickness of either the cassette 10 or 50. The buttresses 74, 76, 78 may be separate inserts attached to the individual outer plates, or may be formed and co-molded with the outer plates so 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 also be molded to curve inward from the outside of the plates toward the actuation or fluid chambers while not increasing the overall thickness of the cassette.

[0028] FIG. 6 shows a rear perspective view of an exemplary cassette 80 including multiple valve stations 82 and an exemplary pump station 84. In one example, the cassette was configured to have a length of approximately 16 cm, a width of approximately 19 cm, and a thickness of approximately 1.5 cm. A first outer or actuation plate 86 is molded with recesses on its outer surface at the valve 82 and pump 84 stations to provide curved inner surfaces to match the associated diaphragms in these regions. In this example, the first outer plate 86, the second outer or liquid side plate 88, and the middle plate 90 each have a nominal thickness of 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 diaphragms have a range of motion approximately equal to the 4.5 mm width of the first interplate space 92. A cassette actuation passage port 96 is shown arranged within the first interplate space 92 of the cassette 80. Thus, a diaphragm travel range of approximately 4.5 mm can be achieved with a cassette having a width of approximately 10.5 mm plus the desired width for the liquid passage of the second inter-plate space 94. In this case, the second inter-plate space 94 has the same width as the first inter-plate space 92, although in other embodiments, the second inter-plate space 94 may be less (depending on the desired flow characteristics for the liquid passage). In this example, the cassette diaphragm travel range is approximately 30% of the overall cassette width. Figure 7 shows a front perspective view of the cassette of Figure 6 revealing the cassette liquid passage ports 98 arranged within the second inter-plate 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, diaphragm retainers or retaining walls 100, 102 are molded as an integral part of the inside of the first outer plate 86. (In a dual-duty cassette, both the first and second outer plates may include retainers or retaining walls 100, 102, since both sides of the middle plate may be pump or valve actuation sides.) In this example, each diaphragm retainer 100, 102 has multiple perforations or holes 104 and, optionally, a top surface groove 106 for evenly distributing actuation pressure across the diaphragm held against the middle plate 90. The curved inner walls 108 of the outer plates 86 at the valve and pump stations are positioned to conform to the associated diaphragm shape when the diaphragm fully expands into the actuation chamber (in which the retainer 102 is located). In some cases, optionally, ribs 109 may be included in the molding of the outer plate 86, the ribs 109 configured to encroach on mating actuation passages in the opposing middle plate. The ribs 109 may be configured with a cross-sectional size and length to adjust the total volume of the associated actuation passages to a predetermined volume (which may help minimize the amount of pneumatic gas volume supplied (or compressed) and improve the responsiveness of the associated diaphragm to actuation by the pressure supply manifold).

[0030] 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 interplate space must accommodate a wider diaphragm range of motion. In such cases, installing actuation volume adjustment ribs can reduce the actuation passage transfer volume and improve cassette performance. Furthermore, where synchronized valve operation is desired, it can be advantageous to match the actuation passage transfer volume between sets of valves that are at varying distances from the cassette actuation port. In this manner, appropriately sized volume adjustment ribs can be used to fine-tune the operation of the cassette valves.

[0031] FIG. 9 shows a perspective view of the actuation side of the mid-plate 90 of the cassette 80. In this example, actuation passages 110, valve and pump station peripheral walls 112, and cassette actuation ports 96 are formed or molded as part of the mid-plate 90. In this example, most of the diaphragm valves or pump stations are supplied by separate actuation passages 110 leading from the dedicated cassette actuation ports 96. The cassette fluid or actuation passages can be individually formed conduits, or each passage can include two walls spanning the inter-plate space, fused to and extending between the mid-plate and either the first outer plate or the second outer plate. In some cases, it may be desirable to operate more than one valve station at a time, in which case a single actuation passage path 114 can supply two or more valve stations, as shown for valve stations 116 and 118. 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 mid-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 rigid consistency. Materials such as other plastics or metals can also be used. Other molding methods, as well as novel technologies such as 3D printing, can be used to form the middle and outer plates. The outer plates can be bonded to the middle plate using adhesives or localized heating via ultrasonic or mechanical vibrations. In a preferred method, the outer plate can be transparent, translucent, or allow transmission of laser wavelengths to allow laser welding of the outer plate to an opaque middle plate. The welds seal the valve and pump areas of the outer plate to the surrounding walls and passages of the individual valve and pump stations in the middle plate.

[0033] Each peripheral wall 112 forms a portion of the actuation chamber of a respective valve or pump station, and each peripheral wall 112 communicates with the actuation passageway 110 via an actuation chamber port 120 in the peripheral wall 112. The pump station 84 in this example has two pump ports 24a, 24b connecting the liquid passageways on the opposite (second) side of the middle plate with the first side of the middle plate shown in the figure. One of these serves as the inlet for the pump chamber, and the other serves as the outlet for the pump chamber. In other embodiments, the pump region can have a single pump port or multiple pump ports. Each of the multiple valve stations in this example has two ports connecting two separate liquid passageways on the second side of the middle plate to the valve station on the first side of the middle plate shown in the figure. Also, in this example, one of the valve ports 34a has a raised peripheral lip 40 to improve sealing of the valve diaphragm against the valve port when positive pressure is applied to the diaphragm.

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

[0035] 11 shows a second side of the middle plate 90 of the cassette 80. In this example, the liquid passage 126 is molded as part of the middle 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 for the pump chamber and the other port functions as an outlet port for the pump chamber. Whether a particular port functions as an inlet or outlet can be determined by which downstream valves are activated or closed.

[0036] FIG. 12 shows a variation of cassette 132 that includes additional optional features (which can 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 the middle plate 134. The first inter-plate space 136 and the second inter-plate space 138 each contain both actuation and liquid passages, as well as actuation ports and liquid cassette ports. In this view, two rows of actuation ports 140, 142 can be seen on the end or narrow side of the cassette, allowing that end of the cassette to plug into a connector or interface that communicates with a pressure distribution manifold. In this embodiment, the overall thickness T2 of the cassette, calculated by adding the thickness of each of the middle plate 134, first outer plate 144, and second outer plate 146 to the width of the first inter-plate space 136 and second inter-plate space 138, allows pump or valve diaphragms to be mounted on the first or second side of the middle plate, or 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 density of pump or valve stations that can be included in cassette 132 can be maximized while minimizing the overall thickness T2 of the cassette, with the contained diaphragm excursion constituting a substantial majority of the cassette's overall thickness. For example, a cassette with such a "double-duty" middle plate (allowing for actuation passages and chambers on both sides of the middle plate) would have a nominal plate thickness of 2 mm, coupled with a 5 mm inter-plate spacing, resulting in an overall cassette thickness of 16 mm to accommodate the 5 mm diaphragm excursion, approximately two-thirds of which constitutes the desired diaphragm excursion.

[0037] 12 and 13 show a dual-duty cassette mid-plate 150 in which a first side 152 and a second side 154 of the mid-plate each include both actuation passages and liquid handling passages incorporating actuation ports, actuation passages, actuation chambers, and liquid passages on each side of the mid-plate. While multiple valve stations 156 are shown in this example, an on-board pump station may also be included in other embodiments. In this regard, the cassette is similar to cassette 132 of FIG. 12.

[0038] Optionally, this mid-plate 150 is additionally designed for use in cassette assemblies incorporating outboard pump pods or liquid mixing pods, since their volume requirements preclude their inclusion as onboard pump or mixing chamber stations on individual cassettes. If a larger stroke volume is required, two or more cassettes can be arranged so that liquid or actuation lines connect to extension conduits 158, 160 perpendicular to the face of the cassettes, connectable to an external pod located between the two cassettes. Conduits (e.g., formed or molded with the mid-plate) originate in the cassette mid-plate and pass through either the first or second outer plate to provide direct connection to an external, self-contained diaphragm pump, self-contained mixing chamber, or self-contained balancing chamber. If the conduits are rigid, they can also function as structural members to help hold the cassette assembly together. The vertical conduits may be used as fluid ports for connection to fluid sources or destinations external to the cassette. In this case, the ends of the conduits may be configured for connection with flexible or malleable tubing. In this type of cassette, the cassette actuation ports and initial portions of the actuation passages can remain entirely within the interplate space of the cassette until the fluid or actuation line reaches the point where it must exit the cassette and connect to an associated pod pump, balancing chamber pod, or mixing chamber. This configuration provides a substantial improvement over previously disclosed cassette assemblies because the cassette actuation ports are more efficiently located. Because the actuation ports are all located along the edges of the cassette, the cassette can be plugged directly into an associated pressure supply manifold or rigid receptacle array without the need for flexible tubing connections or separate connectors.

[0039] The cassette midplate 150 of FIGS. 12 and 13 also illustrates that actuation and liquid passageways can be routed from a first side of the midplate to an opposite second side to increase the number of valve or pump stations that can be incorporated into a particular size cassette. Routing actuation or liquid passageways can be complicated by the presence of other passageways, pump stations, or valve stations that block a direct route from the cassette ports to the desired valve or pump station. In this case, redirecting the actuation or liquid passageways to the first / second side of the midplate can allow the passageways to bypass obstructing structures on the second / first side of the midplate. The bypass passageways may simply penetrate to the opposite side of a single midplate, or they may penetrate the midplate, bypass obstructing structures, and then return to the starting side of the midplate to reach the desired pump or valve station. FIG. 14 illustrates the second side 154 of the cassette midplate 150. Actuation port 162 configured to supply valve station 164 lacks an uninterrupted path to the valve station due to the presence of extension conduit 168. Actuation passageway 170a connected to cassette actuation port 162 terminates in actuation passageway port 172 that penetrates mid-plate 150. As shown in FIG. 13 , actuation passageway 170b on first side 152 of mid-plate 150 can connect actuation passageway 170a to actuation passageway 170c via actuation passageway port 174 to complete the actuation passageway path from cassette actuation port 162 to valve station 164.

[0040] Whether or not a cassette includes actuation passages and chambers and liquid passages on both sides of the midplate (i.e., a dual-duty midplate), the cassette can be arranged with liquid cassette ports located on the narrow side or end of the cassette, such that multiple or banks of such cassettes can be stacked together to form a compact cassette group. Figure 15 is a rear perspective view of a cassette group 176 consisting of multiple individual cassettes 178a-d stacked wide side to wide side. Each cassette 178a-d has one or more cassette actuation ports 180 located on the narrow side of the cassette within first interplate spaces 182a-d, the actuation ports facing the same direction so that individual cassettes of the cassette group can be plugged into individual corresponding connector or receptacle ports of a receptacle assembly that is positioned adjacent to one another and connected, mounted, or attached to a pressure distribution manifold.

[0041] The cassettes of a cassette group can be positioned so that they contact each other, regardless of whether they are bonded or glued together. Alternatively, they can be positioned adjacent to each other with play or some spacing so that each cassette of the group can be individually inserted or removed from its corresponding receptacle assembly without disturbing adjacent cassettes. This allows individual cassettes to be positioned on rails or tracks to properly align the actuation ports with the individual connectors or receptacles, making insertion and removal easier. The cassette receptacle assemblies can be positioned adjacent to each other to provide a spatially compact cassette group. Optionally, the cassette receptacle assemblies can be positioned within a single housing, which can provide alignment and insertion / removal tracks for the individual cassettes. Alternatively, each cassette receptacle assembly can be included in a separate housing for the same purpose. In settings that provide individual fluid circulation to an array of interest, this configuration allows a single cassette to be exchanged for one having a different mechanism (in terms of the number and distribution of pump and valve stations, and liquid flow paths). Thus, as the fluid circulation requirements for an individual subject change, the configuration of the cassette group allows the cassette to be conveniently and quickly adapted according to the needs of its associated subject. Furthermore, adjacent cassettes in a cassette group can be interconnected via their respective liquid ports, for example, by jumper lines. In this way, complex liquid mixing procedures can be performed when a solution containing a specific component at a specific concentration needs to be provided to a subject. Thus, one or more cassettes in a cassette group can be dedicated to a single subject, as needed.

[0042] FIG. 16 is a front perspective view of the cassette group 176 of FIG. 15. In this example, for ease of illustration, the cassette liquid ports 184 are located on the narrow side of each cassette 178a-d opposite the actuation port 180. While the actuation ports are preferably located at the same corresponding end of the cassette (so that a pressure distribution manifold can be located behind the cassette group), the liquid ports of an individual cassette need not all be located along the same end of the cassette. In this embodiment, the cassette liquid ports 184 are located within the second interplate spaces 186a-d of each cassette 178a-d. Thus, the cassette group 176 can be oriented to face outward from one or more receptacle assemblies (not shown) connected to, mounted on, or attached to the pressure distribution manifold. Because each cassette 178a-d can provide liquid circulation to an individual target, the number of individual cassettes in the group can be matched to the number of targets requiring liquid circulation. For example, multiple biological cell stations, tissues, or organs arranged for growth, experimentation, or testing can be supplied with circulating fluids, drugs, nutrients, or other chemicals by multiple cassettes in a cassette group, with each cassette potentially supplying liquid solutions of similar or different compositions to each cell, tissue, or organ station. Cassette groups, such as cassette group 176, can also be configured to function as solution mixing stations, with the liquid output of one cassette in the group providing the liquid input for adjacent cassettes in the group, allowing for complex solution mixing protocols. Thus, two or more cassettes can be reconfigured to supply a single subject.

[0043] FIG. 17A shows a rear perspective view and FIG. 17B shows a front perspective view of a cassette group 186 incorporating dual-duty intermediate plate cassettes 188a-d. In other embodiments, a cassette group can incorporate one, two, or more dual-duty intermediate plate cassettes among one or more single-duty intermediate plate cassettes. In this example, actuation ports 190 of representative second interplate spaces 182a-d and liquid ports 192 of representative first interplate spaces 186a-d are shown. Depending on the number and size of the individual pump and valve stations within cassettes 188a-d, the use of dual-duty intermediate plate cassettes may enable a higher density of multi-purpose valve 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 the liquid chamber exceeds the volume that the onboard pump or chamber can accommodate. In this case, an outboard pump or chamber pod is used and placed between the two cassettes. Liquid and / or actuation lines originate from opposite sides of the two cassettes to supply the outboard pump or chamber, allowing liquid to flow, for example, from the first cassette to the outboard pod and then to the second cassette, with each cassette housing an upstream or downstream valve station to control the liquid flow. Alternatively, the outboard pump actuation line could originate from the first cassette's face, and the liquid inlet and outlet lines could originate from the second cassette's opposite face. This type of cassette assembly could also connect liquid lines directly from one cassette's face to the opposite cassette's face. In prior embodiments, as shown in Figure 18, opposing faces of cassettes 194, 196, 198 included actuation ports 200 for onboard pump stations and actuation ports 202 for valve stations, along with liquid ports 204, liquid lines 206 and actuation lines 208 to outboard pumps 210 or chambers 212. This configuration resulted in numerous flexible tubing connections for both liquid and actuation lines being threaded into the interior surfaces of the cassettes, creating challenges with respect to manufacturing, assembly, and maintenance.

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

[0046] Dialysis Cassette Assembly FIG. 20 illustrates an example of a cassette assembly 226 that performs substantially similar fluid processing functions as the conventional cassette assemblies of FIGS. 17A, 17B, and 18 and helps explain how the cassettes of the present disclosure substantially improve the construction, assembly, and maintenance of such cassette assemblies. In this example, the illustrated cassette assembly 226 is used to mix, process, and move dialysate within a portable hemodialysis machine. However, the use of this type of cassette or cassette assembly (i.e., a cassette having end-mounted actuation ports with actuation passageways extending between plates and parallel to the cassette face) is not limited to hemodialysis systems. As shown in FIG. 20, three cassettes 228, 230, and 232 are coupled together by fluid processing pods 234 and 236. These inter-cassette pods may include self-contained diaphragm pumps with both actuation and fluid conduits, or other fluid transfer chambers 236 with only fluid conduits. Other examples of fluid transfer pods include fluid mixing chambers or fluid balancing pods, in which flow through a first fluid line is balanced by 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 processing pod 234, 236 is fluidly connected to one or both of its adjacent cassettes by either flexible or rigid conduits. Rigid liquid conduits 238 may be preferred because they can provide structural support for the cassette assembly. In the case of a diaphragm pump pod 234, both the liquid transfer conduit and the actuation conduit may extend to one or both of its adjacent cassettes. The conduits 238 penetrate the faces of the adjacent cassettes to reach fluid or actuation passageways located within the first or second interplate spaces of that cassette. Generally, the actuation passageways driving the inter-cassette pump pods proceed uninterrupted from the cassette actuation ports to the pump pod's actuation chambers. The fluid passageways of either the inter-cassette pump pod or another type of fluid processing pod connect to corresponding inter-plate fluid passageways of one or both adjacent cassettes through one or more diaphragm valves located within the cassette.The actuation passages of these diaphragm valves, the actuation passages of the pump pods, and any other actuation passages within the cassettes traverse the first or second inter-plate space of each cassette to a first end of the respective cassette and terminate at the cassette's actuation port 240. In the cassette assembly, each cassette 228, 230, 232 has its actuation port 240 located on the narrow side or end of the respective cassette and is configured so that the actuation ports of the cassette assembly all face the same direction, occupying one side 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 motion. This configuration eliminates the need for flexible tubing to connect the cassette actuation ports to corresponding manifold output ports. In the example illustrated in FIG. 20, cassette 228 is optionally configured as a single-duty mid-plate cassette (all actuation ports are located in either the first or second inter-plate space). In the same example, cassettes 230 and 232 are optionally configured as dual-duty mid-plate cassettes, with several actuation ports located in both inter-plate spaces on both sides of cassette mid-plates 242, 244. Other arrangements are of course possible depending on the fluid processing tasks required of a similarly configured cassette assembly.

[0047] FIG. 21 shows a partially exploded view of the exemplary cassette assembly 226 shown in FIG. 20. The assembled cassettes 228, 230, and 232, along with the inserted pump 234 or other fluid transfer chamber 236, are held within a frame assembly to ensure proper alignment of the cassette ports during installation and operation. Previously disclosed cassette assemblies could rely on rigid conduits (e.g., conduit 238) and several retaining bars or springs to hold the assembly together (see FIG. 18), but did not require precisely aligned actuation ports to plug directly into the manifold assembly. In the cassette assemblies disclosed herein, carrier frames 505 and / or 507 can eliminate this concern by compactly securing the cassette assembly 226 and holding it in the required configuration or alignment. The exemplary embodiment of FIGS. 20 and 21 shows a first carrier frame 505 and a second carrier frame 507 that can engage the cassette assembly 226 from opposite directions. Some embodiments may provide similar carrier frames for securing the cassette assembly 226 from adjacent sides, while other embodiments may provide a monolithic carrier frame for securing the cassette from two or more pairs of opposing sides.

[0048] Carrier frames 505 and 507 may further include plate rails that can slide over corresponding cassette plates of cassettes 228, 230, and 232 to engage cassette assembly 226. By interconnecting the frame components and securing the enclosed cassette plates to the rails, there is no need to puncture or drill holes in any of the three cassette plates to secure them to the frame. The rail configuration and lack of screws, nuts, or clips through the cassette plates may reduce the possibility of damaging the cassette assembly and interfering with any of the pneumatic connections or pathways therein. For example, first carrier plate 505 may include a first set of plate rails 505A, 505B, and 505C, and second carrier plate 507 may include a second set of plate rails 507A, 507B, and 507C. Plate rails 505A, 505B, 505C, 507A, 507B, and 507C can include elongated slots that can partially or completely receive at least one end or a portion of an end of a corresponding cassette plate of cassettes 228, 230, and 232. For example, with reference to first carrier frame 505, plate rails 505A, 505B, and 505C can receive the ends of cassette plates of cassettes 228, 230, and 232, respectively. In one embodiment, the rails can include capping features. For example, rails 505A and 505C of first frame 505 can include capping features 505F and 505G disposed at the ends of the respective rails. Plate rails 507A, 507B, and 507C can engage with cassette assembly 226 by receiving the ends of corresponding cassettes 228, 230, and 232. Additionally, the walls of the plate rails 505A, 505B, 505C, 507A, 507B and 507C may also optionally include notches 506 configured to receive and cradle corresponding rigid liquid conduits 238 when the carrier frames 505, 507 are engaged with the cassette assembly 226.Plate rails 505A, 505C, 507A, and 507D can have closed and open ends. The open ends of the rails can be included to avoid interference with nearby cassette ports 240. Note that first and second carrier frames 505 and 507 can slide over their respective cassette ends to engage cassette assembly 226 and may not require additional fastening devices to directly engage cassettes 228, 230, and 232. Furthermore, fastening features complementary to the rails, such as, but not limited to, capping features 505F, 505G, and notches 506 and 508, can further strengthen the engagement between the cassette assembly and the frame, thereby distributing any forces applied to the frame more evenly on the cassette assembly, potentially avoiding distortion or deformation of cassette assembly 226. This configuration can facilitate compact installation and removal of the cassette assembly 226 from the array of manifold receptacles of the hemodialysis machine 246 without creating difficulties with the cassette assembly that could result in misalignment of the cassette ports.

[0049] Plate rails 505A, 505B, and 505C may be interconnected by upper and lower bars 505D and 505E that extend perpendicular to the plate rails. Lower bar 505E interconnects plate rails 505A-505B and 505B-505C near the open ends of the rails and cassette ports 240. Upper bar 505D interconnects plate rails 505A-505B and 505B-505C near the closed ends of the rails. Similarly, rails 507A, 507B, and 507C are interconnected by upper and lower bars 507D and 507E that extend perpendicular to the plate rails. Lower bar 507E interconnects plate rails 507A-507B and 507B-507C near the open ends of the rails and cassette ports 240. An upper bar 507D interconnects plate rails 507A-507B and 507B-507C at the closed ends of the rails.

[0050] At least one crossbar 511 may be positioned to connect the first and second carrier frames 505, 507 when the frames are positioned to engage the cassette assembly 226. In this example, the crossbar 511 is positioned to pass longitudinally through the cassette assembly 226 and connect the first and second carrier frames 505, 507 at opposite ends of the crossbar. This configuration helps stabilize the sides of the frames 505, 507 near the ports 240 of the cassettes 228, 230, 232. The crossbar 511 helps prevent the frames 505, 507 from shifting position relative to the cassette assembly 226. The connection between each end of the crossbar 511 and the corresponding carrier frame 505, 507 may be established by a fastening mechanism, such as, but not limited to, screws, bolts, adhesive, laser or ultrasonic welding, or other similar fastening mechanisms. Optionally, the cassette assembly 226 may provide alternative or additional connection elements between the first carrier frame 505 and the second carrier frame 507 to secure them to one another, which may include, but are not limited to, clips similar to clip 512 of FIG. 18, threaded rods, or zip ties, or other elements that limit the extent to which the frames 505, 507 can shift relative to one another.

[0051] 20 and 21 further illustrate a first support plate 513 and a second support plate 515. The first support plate 513 can be positioned 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 positioned on a side of the cassette assembly 226 that is perpendicular to the side on which the first and second carrier frames 505, 507 are positioned. Additionally, the first support plate 513 is positioned on the carrier frame opposite the cassette port 240. The first support plate 513 can further include flanges 513A and 513B at opposite ends. These flanges 513A, 513B can be configured to engage with the top bars 505D, 507D of the first carrier frame 505 and the second carrier frame 507. The first support plate 513 can be mechanically secured to the top bars 505D, 507D with clips, screws, or the support plate 513 can be bonded to the top bars 505D, 507D. Alternatively, the top plate 513 and at least one of the frames 505, 507 can be molded together. The first support plate 513 can engage with the top bars 505D, 507D when the carrier frames engage with the ends of the cassettes 228, 230, 232 of the cassette assembly 226. Thus, the first support plate 513 and cross bar 511 can secure 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, crossbar 511 and first support plate securely holds the cassette assembly 226 and helps to distribute external mechanical forces more evenly among the components of the cassette assembly, preventing distortion of their relative positions.

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

[0053] FIG. 21 also shows a second support plate 515 that can optionally be included to engage 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 is attached to the frame via a connecting element 519. The connection can be achieved by receiving the connecting element 519 in a corresponding connecting 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, but not limited to, the second support plate 515, as a single component. Flexing or twisting 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 separately attached to the frame. Additional support elements similar to support plates 513, 515 and support brackets 523 may be provided to complement carrier frames 505, 507 and hold the required alignment of cassette assembly 226.

[0054] 22A and 22B show perspective views of an exemplary first support plate 513. The flanges 513A and 513B can further provide an engagement mechanism, such as, but not limited to, a resilient clip or gripper 514. The first support plate 513 can also include one or more clips 514 on the flange-free side. The clips 514 can be configured to engage with the ends of the carrier frames 505 and 507. For example, the clips 514 can be configured to engage with the top bars 505D, 507D. Alignment elements, such as one or more nubs 516 ( FIG. 21 ), can be included on the ends of the carrier frames 505, 507. The nubs 516 can serve as alignment mechanisms 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 may include longitudinal and / or lateral stiffeners 517 to reduce mechanically induced deformation of the first support plate 513 .

[0055] 23 shows a hemodialysis machine 246 configured to enclose a cassette assembly 226. A front panel 248 is configured to include a dialyzer recess and holder 250 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 the enclosure of the machine 246 behind the front panel 248.

[0056] FIG. 24 shows the enclosure 254 of the device 246 of FIG. 23 with the front panel 248 and other components removed. The interior configuration of the enclosure or housing 254 allows the cassette assembly 226 to be placed on an interior 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, tubing for the 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 is a recess 258 configured to hold a pressure distribution manifold (in this case, a pneumatically actuated manifold) with electromechanical valves and one or more electronic controllers, at least one of which is configured to control the manifold's electromechanical valves. These components are located outside the enclosure 254 to help protect them from the high temperatures that may be used when sterilizing the fluid-transporting components of the hemodialysis device 246. 25 shows a rear perspective view of enclosure 254 highlighting recess 258 located beneath ledge 256 of enclosure 254. Thus, the pressure distribution manifold can be located beneath cassette assembly 226, with the cassette assembly located within enclosure 254 and the pressure distribution manifold located outside of enclosure 254.

[0057] Loading and Locking the Cassette Assembly 30 and 31 illustrate the installation and retention of cassette assembly 226 within enclosure 254. In FIG. 30, cassette assembly 226 is elevated directly above three cassette receptacle assemblies, aligning the three arrays of cassette actuation ports 240 with the individual receptacle ports on adapters 266, 268, and 270. The receptacle assemblies are configured to match the actuation port arrays of cassette assembly 226 with actuation outlets of a pressure distribution manifold located outside the enclosure below shelf 256. Lowering cassette assembly 226 allows cassette actuation ports 240 to engage with the individual adapters via press-fit connections. Sealing of the individual actuation ports 240 can be achieved using O-rings, gaskets with elastomeric wiper seals, or other means commonly used to seal press-fit connections. The adapter, in turn, can provide a direct connection to an output port of the pressure distribution manifold ( FIGS. 32-37 ) located below the shelf 256 and outside the enclosure 254. FIG. 30 further illustrates a cassette loading device 292 capable of receiving the cassette assembly 226 and holding it in place during installation. A handle 308 belonging to the loading device 292 can operate to lock the cassette assembly within the enclosure 254. A detailed description of the operation of the device 292 and handle 308 for locking and holding the cassette assembly is provided below with reference to FIGS. 56-59 . In one configuration, the loading assembly of FIG. 30 can be in an open position showing the operating handle extending parallel to and away from the cassette assembly. FIG. 31 illustrates the operating handle 308 tilted downward, indicating that the cassette assembly 226 has been locked into the cassette-receiving space by moving the loading device toward the manifold's receptacle assembly, thereby pushing and securing the cassette assembly 226 into the corresponding adapter port.In this example, loading device 292 can include a force-applying element, such as, but not limited to, one or more bars that can interact with first support plate 513 ( FIGS. 22A and 22B ) and can be manipulated by handle 308. Lowering handle 308 can allow the force-applying element to press against first support plate 513. This force can be transmitted to cassette assembly 226 through cassette frames 505, 507, which press cassette assembly 226 toward adapters 266, 268, and 270. FIG. 31 shows cassette assembly 226 in an operable configuration, i.e., pressed to align the array of cassette actuation ports 240 with their respective adapters 266, 268, and 270. Note that handle 308 in FIG. 31 is shown in a closed position. That is, the cassette assembly 226 is locked inside the enclosure 254 and the handle is positioned to allow installation without interfering with the front panel of the hemodialysis machine.

[0058] The hemodialysis machine 246 of the embodiment shown in Figures 45 and 46 includes an enclosure 254 in which the footprint of the cassette assembly 226 extends in a forward direction of and overhangs the shelf 256. To this end, as shown in Figure 45, a group of manifold interfaces or adapters 266, 268, 270 are configured to extend in a forward direction of the shelf 256. The adapters 266, 268, and 270 provide the necessary mating between the actuation port 240 of the cassette assembly 226 and individual connector or receptacle ports 272 disposed on the interfaces or adapters 266, 268, 270. The adapters 266, 268, 270 in this example function as a receptacle assembly, providing an array of receptacle ports for mating with the cassette ports 240 arranged on each of the cassettes 228, 230, and 232, respectively. 46 shows a bottom perspective view of enclosure 254 with interface / adapters 266, 268, 270 installed. This view reveals the extent to which the adapters overhang enclosure shelf 256 (and therefore pressure supply manifold 260). Adapters 266, 268, 270 serve to map the elongated array of cassette ports along the ends of the individual cassettes to a more spatially compact array of manifold ports located in risers or upper blocks 276A-C between adapters 266, 268, 270 and the underlying upper block 274 of pressure distribution manifold 272.

[0059] Pressure Distribution Manifold FIG. 26 shows a schematic diagram of one embodiment of a pressure distribution manifold (or manifold assembly). The manifold assembly is configured to selectively provide air pressure (positive, negative, or atmospheric) to control pneumatically driven pumps and / or valves on two separate pump cassettes. In this modified embodiment, a first set of air pressure outlets is configured for direct connection to a first pump cassette or cassette assembly (i.e., direct plug-in connection to the manifold assembly or to an adapter directly connected to the manifold assembly). In one embodiment, the direct connection interface is shown schematically as one or more risers or “top blocks” 276A, 276B located on the upper side of the manifold assembly 260. The top block includes a direct connection port 261 configured to directly connect to a first pump cassette (not shown), which can be located directly above the manifold assembly 260. The manifold or manifold assembly also includes a second set of air pressure outlets configured to indirectly connect to a second pump cassette via flexible or malleable tubing. 26 also shows an exemplary fitting 582 for indirect connection to a second pump cassette (not shown), the connection being configured for flexible or malleable tubing that travels some distance to a second pump cassette located remotely from manifold assembly 260. In the context of the hemodialysis machines 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 (located further away from the front panel of the machine) can be configured for pneumatic connection to the manifold assembly via flexible or malleable tubing to multiple fittings (here represented by exemplary fitting 582).

[0060] FIG. 26 also illustrates another improvement in the manifold assembly 260 that helps prevent or reduce the accumulation of particulates or liquid debris on the internal sealing surfaces of the electromechanical pneumatic control valves. The exemplary valve 267 is shown generally horizontal. The internal valve seat or sealing surface is oriented to avoid horizontal surfaces on which debris can accumulate. In the schematic views of FIGS. 26-29, a lower or bottom manifold block 272 mates with an intermediate manifold block 274. The lower manifold block 272 has a cross-sectional "T" shape (transverse to the longitudinal axis "Z" of the manifold assembly 260) including a horizontal portion 272A and a depending portion 272B, with multiple valve mounting surfaces and openings located on the depending portion 272B. The exemplary valve 267 is shown mounted on one such surface and above one such opening. A valve face seal (not shown) is envisioned to couple the valve body and the mounting surface of the depending portion of the manifold. Depending portion 272B is shown as having a vertical orientation relative to horizontal portion 272A for convenience. Depending portion 272B may have a non-vertical orientation, such as an upward slope that causes the valve mounting surface and opening to orient the valve body and face seal in a downward angular orientation. This angled orientation also helps prevent the accumulation of liquid (e.g., liquid condensate) or waste products on the valve components having the sealing surface (e.g., the valve seat). In many (but not all) valve embodiments, the associated internal valve plunger or piston operates in a horizontal or near-horizontal orientation, as represented by valve 267 shown schematically in FIGS. 26-29.

[0061] 26-29, the pressure source lines 263 are shown embedded within the lower or bottom manifold block 272. Depending on how the internal pneumatic passages within the manifold assembly 260 are plumbed, these pressure source lines may also be located within the intermediate block 274. In the illustrated schematic, each of the plurality of valves 267 receives an input line from one of the pressure source lines 263 and has an output line ultimately connected to an output port of the manifold assembly (either the direct connection port 261 or the indirect connection port 582).

[0062] FIG. 27 shows a schematic diagram of an embodiment of a manifold assembly 260 in which direct connection blocks 276A, 276B are flared, cantilevered, or offset relative to the body of the manifold assembly. In this illustration, the longitudinal axis ("Z") of the manifold assembly can be adapted to accommodate pump cassettes of any longitudinal length. However, if the pump cassette is configured with an array of inlet ports that exceeds the main front-to-back ("X") dimension of the manifold assembly, the direct connection blocks can be positioned to flared from the manifold assembly in that direction. Ports 261 are then connected to passages in blocks 276A, B for routing to a more compact array of one-to-one mapped ports on top of intermediate block 274.

[0063] FIG. 28 shows a schematic diagram of an embodiment of the manifold assembly 260 in which an array of pressure sensor ports 567 is located between direct connection blocks 276A and 276B. In this case, various pneumatic passages within the manifold assembly may have branched or in-line connections to sensor port 567A of the pressure sensor array 567. In most cases (but not necessarily all), these passages connect to the output lines of the pneumatic control valves and to output ports of the manifold assembly to which the valve output lines are connected. In one example, the array of pressure-sensing ports may be configured to mate with a printed circuit board (PCB) located above the array and containing a corresponding array of pressure sensors. The pressure sensors on the PCB may be connected to a hemodialysis controller. The hemodialysis controller uses the pressure information to control the pneumatic control valves to provide predetermined levels and patterns of pressure to the pumps or valve targets in the connected pump cassettes.

[0064] FIG. 29 shows a schematic diagram of one embodiment of a manifold assembly 260 including one or more manifold adapter or interface blocks 266, 268. In this example, top blocks 276A, 276B function as risers that provide spacing between an attached direct-connect pump cassette and the main body of the manifold assembly 260. The risers may include pneumatic passages connecting multiple 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 blocks can be configured to spatially redistribute the relatively closely spaced output ports 261a within the riser blocks or other blocks of the manifold into a differently spaced array or distribution of output ports 261b. In this manner, the direct-connect output ports of the manifold assembly can be spatially arranged or redistributed to match the corresponding input ports of the corresponding direct-connect pump cassettes. Thus, the manifold adapters 266, 268 include transfer ports on a first side that mates with the manifold 274 or its associated riser 276A, B, which map to corresponding transfer ports 261b on the opposite second side that mates with the pump cassette assembly. Thus, a first array of manifold output ports having a first spatial port configuration can be directly mated with 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 cantilevers off the front face of the manifold. These features help separate 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 embodiments herein, the manifold assembly can be made as compact as allowed by valve, passage, and port constraints, while retaining the ability to interface with pump cassettes that may have substantially different spatial constraints or spatial array requirements for their actuation ports.

[0065] Figures 32 and 33 show details of one embodiment of a pneumatically actuated manifold in the form of a pressure distribution module 260. The pressure distribution module 260 provides selectable pneumatic connections from multiple pressure sources to cassette assemblies that plug into receiving ports on the platforms of manifold adapters 266, 268, and 270. The pressure distribution module 260 can further provide selectable pneumatic connections to remote cassettes via flexible or malleable pneumatic lines (not shown). The pneumatic connections are selectively controlled by digital or binary pneumatic valves 262, 265, and 267 mounted in or on the manifold block. One or more controllers control the state of the valves based on signals received from pressure sensors mounted in the top block 276 and, in the case of a hemodialysis machine, provide programmed instructions for selectively actuating the valves to pump blood, dialysate, and water to provide dialysis treatment to the patient.

[0066] The pressure distribution module 260 controls the operation of the pneumatically actuated diaphragm pumps and pneumatically actuated liquid valves by selectively connecting them to one or more pressure reservoirs via digital or binary electromechanical valves. The electromechanical valves may include two-way or three-way digital valves. The digital valves may have two positions. Two-way digital valves are either open or closed. Three-way digital valves connect a common port to either a first port or a second port. One or more controllers control the state of the valves 262, 265, and 267 based in part on signals received by the one or more controllers from pressure sensors 565 (see FIG. 34). The pressure reservoirs may include a high positive pressure reservoir, a low positive pressure reservoir, a negative pressure or vacuum reservoir, and a vent to atmosphere.

[0067] The pressure distribution module 260 can be assembled from multiple 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 port 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 prevent waste or liquid buildup within the valves, which could impair their function or shorten their maintenance-free lifespan. Pressure sensor 565 (FIG. 34) is mounted in port 567 on the upwardly facing surface of end manifold block 276. Adapters 266, 268 and 270 provide ports 266P, 268P, 270P for receiving port 240 of 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 the entire length of the manifold blocks 272, 274. The ports for the internal supply lines are capped 264 or have ports 263 for flexible tubing connections to pressure reservoirs. Both end faces of the manifold blocks 272, 274 may include ports for connecting the internal supply lines (not shown) to external pressure reservoirs.

[0069] Multiple diaphragm pumps and diaphragm valves can be grouped into a single cassette, as shown in Figures 6-13. Multiple such cassettes can be joined together to form a cassette assembly 226, as shown in Figures 20 and 21. In this case, the assembly spaces the cassettes apart to accommodate outboard pumps, and the mixing or fluid balance chambers have a larger volume than can be accommodated in any one of the individual cassettes. Pressure distribution module 260 includes adapters 266, 268, and 270 that extend perpendicular to the longitudinal axes of manifold blocks 272, 274, and 276. The adapters expand the interface area of ​​the pressure distribution module from the footprint of the manifold blocks and risers to any area necessary to accept port 240 of cassette assembly 226. The pneumatic layout and port distribution on and within adapters 270, 268 and 266 and their subcomponents (not shown) allows for a direct connection between cassette assembly 226 and manifold blocks 272, 274, 276, with a one-to-one mapping of each port on the cassette assembly to a corresponding actuation port on the manifold assembly.

[0070] The external pressure reservoirs to which the pressure distribution module 260 may be connected may have a capacity maintained at a specified or predetermined pressure by pumps controlled by the system controller. In one embodiment, the high-pressure reservoir may be maintained at a pressure of approximately 1050 mmHg, and the positive-pressure reservoir may be maintained at a pressure of approximately 800 mmHg. The actual pressures supplied to the various pneumatically actuated pumps and valves may vary based on the pressure reservoirs ported by the two-way and three-way valves of the pressure distribution module 260. Additionally, intermediate pressures may be supplied by a combination of rapid opening and closing of on-off valves. Generally, a high-pressure source may be useful for actuating diaphragm valves to ensure reliable valve closure without leaks during cassette assembly operation.

[0071] 33 shows an exploded view of the pressure distribution manifold 226. The manifold blocks 272, 274, and 276 may further include intermediate element connections between each of the manifold blocks 272, 274, and 276. These intermediate elements and connections may serve to assemble the three manifold blocks and establish pneumatic connections between the individual manifold blocks 272, 274, and 276. The first set of intermediate components may include, for example, a first plate 550, a first gasket 552, and a second gasket 554 that may be used between the T-shaped manifold block 272 and the intermediate manifold block 274, and the second set of intermediate components may include a second gasket plate 555, a third gasket 556, and a fourth gasket 558 that are disposed between the intermediate manifold block 274 and the end manifold block 276. The two manifold blocks 272, 274 can be clamped together with a gasketed intermediate plate 550 between them. The intermediate plate 550 can be referred to as a backing plate because it provides a rigid surface that forces gaskets to seal against the multiple passages that may 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 surface 276G, 274F, 272F (see Figures 33, 35, 36) with passages and various ports that mate with the ported plates and gaskets (such as plates 550, 555 and gaskets 552, 554, 556, 558). Each passage can be configured as a groove including a solid bottom and two sidewalls with an open top. The passages may be cut into one face 276F, 274F, 272F of the manifold block or may be formed by a wall extending above the surface of the manifold block faces 276F, 274F, 274G and 272F. As shown in Figure 33, the open tops of the passages may be sealed by clamping gaskets 554, 552, 556, 558 backed by rigid flat middle plates 550, 555 against the passages.In one example, middle plate 550 is a backing plate that presses gasket 552 against all passages on face 272F and urges gasket 554 against passages on face 274G. Note that face 274G is opposite face 274F in FIG. 33. The manifold blocks and gaskets can include features that ensure essentially uniform distribution of pressure on the gaskets. Middle plate 550 provides a substantially smooth, rigid backing for the gaskets so that multiple manifold blocks can be assembled or sandwiched together into multi-component pneumatic manifold 260. The passages are linked to pressure sources, valves, sensors, and outlet ports on the other faces of the blocks. Manifold blocks 276, 274, 272 can be assembled by sandwiching gaskets 552, 554, 556, 558 and intermediate plates 550, 555 between them with mechanical fasteners 570 to seal the multiple passages on the passage-formed faces 272F, 274F, 274G, 276G of each of manifold blocks 272, 274, 276. This sandwich construction allows for compact assembly of multiple manifold blocks with multiple sets of passages on one face of each block 272, 274, 276.

[0072] The connection points of T-shaped manifold block 272 can be configured to receive threads that extend through other components that assemble pressure distribution manifold 260 as a unit. In this example, matching connection points 572 can be provided on first gasket plate 550, connection points 573 on middle manifold block 274, and connection points 574 on third and fourth gaskets 556, 558. First set of valves 265 can operate on pneumatic paths within manifold blocks 272, 274, and 276 and / or on pneumatic paths connecting manifold blocks 272, 274, and 276.

[0073] 32 and 33 illustrate an embodiment including multiple cartridge valves 265 and connections to a pressure reservoir 263. The cartridge valves are inserted into manifold ports. Corresponding cavities (not shown) are formed on the outside of the cartridge valves 265 to accommodate seals. The machined cavities may have a set of dimensions specified by the valve manufacturer to ensure sealing and proper function of the cartridge valves 265. While the number may vary in other embodiments, in this particular embodiment, approximately 48 cartridge valves 265 are mounted on the side of the intermediate manifold block 274. This side of the intermediate manifold block 274 is perpendicular to the face 274F in which the passages are formed. In some embodiments, the cartridge valves are three-way valves, such as the Lee LHDA plug-in valve, available from 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 connect cassette assembly and the remote connect cassette assembly (if required), and a linear array of electromechanical valves extends 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 in pneumatic communication with other pneumatically actuated valves, diaphragm pumps, pneumatic cylinders, and remote cassettes containing diaphragm valves and pumps. In one example, the pressure distribution module 260 controls the position of the occluder 251 in FIG. 23 , which includes a pinch valve for blocking the blood line and is actuated by a pneumatic cylinder. In another example, the pressure distribution module 260 can be positioned in pneumatic communication with the dialysate tank to perform tank volumetric measurements using pressure information. Additionally, the pressure distribution module 260 can be configured to control the pumping action of a blood pump cassette (not shown) attached to the blood pump cassette receptacle assembly 252 in FIG. 23 . Referring now to FIG. 34, port 582 shown in T-shaped manifold block 272 can connect directly to one or more blood pump cassettes or can connect via flexible or malleable tubing to establish the necessary pneumatic connections. Port 582 includes fittings that connect to pneumatic tubing and can be individually detachable from T-shaped manifold 272. Pneumatic lines connected at one end to port 582 can be connected at the other end to connectors on the surface of dialysis machine wall 255 ( FIG. 24 ). A second connector within the housing can be connected using flexible tubing to, for example, a dialysate tank, a pneumatically actuated tubing occluder, and / or the blood pump cassette receptacle assembly 252.

[0075] Cartridge valve 265 and surface-mounted valve 267 in this embodiment control the air pressure supplied to the occluder, blood pump cassette, and other pneumatically driven components within hemodialysis machine 246. Pressure distribution module 260 is mounted to the rear wall of enclosure 254, and mounting mechanisms such as standoffs 580 can be provided to position adapters 266, 268, 270 relative to enclosure 254.

[0076] Continuing with reference 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 or three-way valve. In some examples, the surface 272F is approximately horizontal, thereby causing the legs of the T-shaped cross section of the manifold 272 to be approximately vertical. In a preferred configuration, the valve-mounting surfaces of the legs are vertical or slightly upwardly angled, so that the ports on the valve 267 are horizontal or downwardly angled to avoid waste or liquid accumulation. The valves can be provided with sealing mechanisms, such as O-rings and / or other elements, to prevent fluid or air leakage. 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 from Parker Hannifin Corporation, Hollis, New Hampshire, USA.

[0077] Referring now to FIG. 34 , air pressure flow through 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 positioned on a surface 567 of the top manifold block 276 in the space between the risers 276A-C. The pressure sensor 565 can be mounted directly to the face 276F of the first end manifold block 276. The pressure sensor 565 can be an integrated circuit soldered to the printed circuit board (PCB) 560. As shown in FIG. 34 , the printed circuit board 560 containing the one or more pressure sensors 565 can be mounted on the top face 276F of the second end manifold block 276, parallel to the passage-formed face, with a gasket to pneumatically isolate each sensor and a plate (not shown) to hold the PCB 560 in place and sufficiently compress 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 fastening components such as screws, nut-and-bolt pairs, rivets, adhesives, or a combination of such fastening mechanisms. An example of a pressure sensor 565 is available from Freescale Semiconductor, Inc., Tempe, Arizona, USA (part number MPXH6250A). A PCB containing 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 actuation chamber of a diaphragm pump or a dialysate reservoir tank. In some cases, the sensors are positioned to monitor the fluid pressure of various diaphragm pumps in the fluid processing cassette. The end manifold block 276 includes risers 276A, 276B, and 276C, which can interface with the respective adapters 270, 268, and 266. The manifold assembly is configured so that the sensor board 560 avoids engagement between the risers and corresponding adapters.The risers also provide separation between the fluid treatment cassette assembly and the temperature sensing sensor board 560, allowing for placement of insulation 269A between the two (see, for example, Figure 48).

[0078] 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 a gasket, a gasket plate, and / or another manifold block. As shown, the base surface 276 can include multiple pneumatic passages 574 sealed by a gasket 558 (FIG. 33). In some examples, the passages 574 can connect a pressure port 567 on the face 276F to holes 261A, 261B, and 261C of the risers. In other examples, the passages 574 can connect the pneumatic pathways or holes to either the pressure port 567 or holes 261A, 261B, and 261C via the gasket 558. The face 276F can include risers 276A, 276B, and 276C, which can serve as mounting surfaces for corresponding adapters 270, 268, and 266, respectively. Pneumatic ports 261A, 261B, and 261C on risers 276A, 276B, and 276C can interface with respective adapters 270, 268, and 266 to transfer air pressure to cassette assembly 226. A fixed connection between riser ports 261A and adapters can be established via mechanical attachments such as nut-and-bolt pairs, threaded or set-screw, or similar mechanisms. Mechanical assembly can also include mating the blocks with intermediate components such as one or more gaskets 568 ( FIG. 32 ), gasket plates, and / or similar components.

[0079] Pneumatic connections in the manifold The structure and function of manifold 260 in FIG. 32 can be further understood by considering the pneumatic pressure sources, conduits, valves, sensors, and outlet ports of manifold 260. In the example illustrated in FIG. 32, manifold 260 has dozens of valves, sensors, and ports. The following sections describe three exemplary pathways, including pressure sources, valves, conduits, ports, and, in one example, pressure sensors. The exemplary pathways help explain how the elements of the manifolds in FIGS. 32 and 33 combine to provide selectable fluid connections between the pressure sources and the actuation chambers of the pneumatically actuated valves and pumps, and to the pressure sensors. The pressure sensors provide information to a controller that controls the valves to safely pump blood, dialysate, and water to provide therapy to the patient.

[0080] The pneumatic manifold schematic in Figure 38 shows the pneumatic connections to the blood pump cassette (which in this case is located on the front panel of the dialysis unit and is therefore connected to the manifold using flexible tubing rather than directional connections). The pneumatic circuit in Figure 38 selectively connects the working chamber of the blood, heparin pump, and associated valves to a high positive pressure source HP, a low positive pressure source LP, or a negative pressure source NEG. Circuit 1005 connects blood pump BP1 to pressure sensor P_BP1, to low pressure source LP via valve V_BP_POS1, and to negative pressure source NEG via valve V_BP_NEG1.

[0081] The blood pump actuation circuit 1005 within the manifold 260 is shown in Figures 39 and 40. The flow paths are holes and passages in 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 runs along the length of the T-shaped manifold block 272. The negative pressure source NEG is a conduit parallel to LP through the long axis of the T-shaped manifold block 272. Positive pressure flows from the LP conduit through a flow path 1012 located at the top of the T-shaped manifold 272 and then through a hole 1020 through the vertical leg 272B of the T-shaped manifold to the electromechanical valve V_BP_POS1. When the valve V_BP_POS1 is open, positive pressure flows through a hole 1025 in the vertical leg 272B to a passage 1040 located at the top of the T-shaped manifold 272. The low pressure then flows through hole 1060 to port 582, where a fitting allows a flexible or malleable line to connect the port to a (remote) blood pump cassette. The pressure in the blood pump connected to port 582 is monitored by a pressure sensor attached to port P_BP1. Port BP1 is located below the two upwardly facing surfaces of upper manifold block 276. Port P_BP1 is fluidly connected to passage 1040 via hole 1057 in upper manifold block 276, passage 1055 in the top of intermediate manifold block 274, and hole 1050 through intermediate manifold block 274.

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

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

[0084] The Mix_DT valve circuit 1100 and the DISINFECT valve circuit 1200 within the manifold 260 are shown in Figures 42 and 43. The flow paths include holes and passages in the various blocks of the manifold 260. Pressure sources ATM, NEG, LP, and HP are conduits located along the longitudinal 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 valve 1105 via passage 1110 and hole 1115 on the bottom surface of the intermediate manifold block 274. The atmospheric pressure source ATM is connected to valve 1105 via passage 1140 and hole 1145 on the bottom surface of the intermediate manifold block 274. Valve 1105 is connected to outlet port V_Mix_DT via passage 1120 on the top of intermediate manifold block 274 , hole 1130 through the upper manifold, and hole 1135 through adapter 268 .

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

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

[0087] FIG. 44 shows a pressure distribution manifold 260 installed in a recess 258 of an enclosure or housing 254. This configuration can allow for proper alignment between ports 261 on the risers of the pressure distribution manifold 260 and the respective ports on the mating faces of adapters 266, 268, and 270. In this embodiment, the manifold 260 is positioned beneath some insulation 264. The insulation 264 can be provided between the body of the manifold 260 and the shelf 256. This configuration isolates temperature-sensitive electronics from heated fluids circulating within the components within the enclosure or housing 254.

[0088] 45 , in this embodiment of the hemodialysis machine 246 and enclosure 254, the footprint of the cassette assembly 226 extends forward from the front of the machine 246. With respect to a user or operator facing the hemodialysis machine 246, the footprint of the cassette extends beyond the leading edge of the shelf 256. To this end, one or more adapters 266, 268, 270 are configured to provide the necessary mating of the working port 240 of the cassette assembly 226 with the respective connector or receptacle ports 266P, 268P, and 270P disposed on the interfaces or adapters 266, 268, 270. The adapters 266, 268, 270 in this example function as receptacle assemblies, providing a first spatial arrangement of receptacle ports that mate with the identically arranged cassette ports 240 of the respective cassettes 194, 196, and 198 of the cassette assembly 226. 46 shows a bottom perspective view of the enclosure 254 attached to the interface / adapters 266, 268, 270. In this view, it is clear the extent to which the adapters overhang the enclosure shelf 256 (and therefore the underlying pressure supply manifold 246).

[0089] FIG. 32 shows how adapters 266, 268, 270 are mounted to the top sides of manifold risers 276A-C and how they overhang the front side of manifold 260. A first spatial array of receptacle ports 266P, 268P, and 270P connects with a second (in this case, more compact) spatial array of output ports 261 in the top block or risers 276A-C of manifold 260. Internal passages within adapters 266, 268, 270 are routed to individual risers 276A, 276B, and 276C mounted above the corresponding arrays of manifold output ports. FIG. 52 shows the manifold / adapter assembly with adapter 266 removed and disassembled to fully reveal the structure of the adapter and risers 276C, 276A, and 276B.

[0090] 47 and 48 are rear views of manifold 260, showing that risers 276A, 276B, and 276C allow adapters 266, 268, 270 to slide from the rear of the enclosure to individual positions within enclosure 254 through slots or notches 280, 282, 284 in shelf 256 of enclosure 254. Risers 276A, 276B, and 276C are made tall enough to allow for placement of insulation (either rigid foam insulation or other types of insulation) to provide a thermal barrier between shelf 256 and the body of manifold 260, as well as to electronic components (control boards, sensors, etc.) located in recess 258 (see, for example, insulation 269A wrapped around the risers in FIG. 48). FIG. 48 shows how the assembly, including manifold 260, its attached risers and adapters 266, 268, and 270, and other associated components, is slid into place as a group within recess 258 of enclosure 254.

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

[0092] Proper alignment of the adapters 266, 268, 270 and pneumatic manifold 260 can be important to ensure that the multiple pneumatic ports 240 of the cassette assembly 226 align with the matching receptacle ports 266P, 268P, 270P to provide the necessary pneumatic connection to the cassette assembly 226. Final placement of the adapters is defined by adapter rails that are securely attached to the same enclosure that attaches the cassette loader 292 to the roof of the enclosure 254. As a result, the retention mechanisms for the above components should be properly positioned to achieve alignment of the pneumatic ports between the three assemblies: the cassette assembly 226, the adapters 266, 268, 270, and the pneumatic manifold 260. FIG. 50 shows the cassette loader 292 with the operating handle 308. The cassette loader 292 can be mounted on the inside surface of the roof 604 of the housing or enclosure 254. As shown, cassette loader 292 and adapter rails 591, 593 and 595 are disposed on opposite surfaces of enclosure 254 and maintain a fixed spatial relationship to one another.

[0093] FIG. 51 shows an example adapter rail 591 that can include a headrest or flange 592 and a tray portion 587 having a raised platform 596, which can partially or completely occupy the tray portion 597. The headrest 592, together with the tray portion 597, form a frame for the rail 591. The tray portion 597 can receive a corresponding adapter, which can rest on the raised platform 596. The tray portion 597 can also include a rail-like profile 594, which can curve to conform to the end of a corresponding adapter received in the rail 591 so 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 rail-like profile 594. The elongated grooves 611 serve to collect any leaking liquid that may risk reaching electronic equipment placed under the shelf 256 or in the recessed area 258 and to direct any leaking liquid or condensation away from the top surface of the installed adapter.

[0094] FIGS. 52 and 53 show exploded views of an exemplary adapter 266 and its interaction with its corresponding riser 276C. More specifically, FIG. 52 shows a top view of multiple plates and gaskets that can collectively form the adapter 266. FIG. 53 shows a bottom view of the same exploded view of the adapter 266. The adapter is positioned to provide individual pneumatic paths between a first array of ports on the cassette assembly 226 and a second array of ports on the pneumatic manifold 260. In this example, the pneumatic ports 240 on the cassette assembly are distributed over an extended surface area that is larger than the narrow dimension of the manifold assembly 260. The adapter functions to converge the first, larger spatial array into a smaller, spatial array of pneumatic ports 261 on the riser of the manifold 260. As shown in FIGS. 52 and 53, the exemplary adapter 266 can include multiple layers or plates containing pneumatic openings and passages that converge into a smaller surface area as the layers progress toward the individual risers. The top plate 280 of the adapter 266 includes pneumatic ports 271 and a connection mechanism 293 for engaging with a subsequent plate of the adapter. The pneumatic ports 271 and connection mechanism 293 are visible through the top view of the top plate 280 in FIG. 52 and the bottom view of the top plate 280 shown in FIG. 53. The top plate 280 rests on an intermediate block 286 that includes corresponding pneumatic ports 285 on a first surface 286A. These pneumatic ports 285 align with the pneumatic ports 271 on the top plate 280. A wiper gasket 282 is received in a gasket receptacle 281 recessed in the first surface of the intermediate block 286. The continuous elastomeric gasket 282, with a wiper seal 284 appropriately positioned, can be formed from a mold. The wiper seal 284 provides sufficient sealing engagement between the cassette port 240 and the corresponding adapter receptacle port 271 while offering lower frictional resistance to installation and removal of the cassette assembly 226 than, for example, individual O-ring seals.

[0095] FIG. 53 illustrates the second, opposing surface 286B of the intermediate block 286. This surface includes pneumatic passages 286C in fluid communication with the ports 281 on the first surface 286A. The passages 285C can be arranged to converge and connect the pneumatic ports 281 on the first surface 286A to the distributed 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 passages 285C ensure that the pneumatic ports 281 converge or shift toward the array of ports on the riser side of the adapter 266. The second intermediate block 290 can include pneumatic ports 288 that match the array of pneumatic ports on the second surface 286B of the intermediate block 286. A second gasket 289 can be disposed between the first intermediate block 285 and the second intermediate block 290. The gasket 289 allows for a proper seal between the first intermediate plate 286 and the second intermediate plate 290 and allows the gasket to be compressed to the extent necessary to form the seal. In one embodiment, a set of alignment features can be provided on the gasket 289 as well as 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. Additionally, the transitional gasket 289 can include air pressure ports corresponding to the air pressure ports 285 on the first intermediate block 286 and the air pressure ports 288 on the second intermediate block 290. A riser gasket 291 can be positioned between the second intermediate block 290 and the corresponding riser (riser 276C in this example). This gasket is positioned to seal the interaction between the second intermediate block 290 and the riser 276C. A plurality of gasket alignment features may be provided on the mating surfaces of the second mid-block 286 and the riser 276C. The foregoing description is intended to also apply to the adapters 268, 270 and the interacting risers 276B and 276A.The number and spatial distribution of pneumatic ports in other adapter-riser interaction embodiments can be, and are, different in this embodiment.

[0096] When there is pneumatic interaction between ports, the sealing components between the ports typically include O-rings. In the case of adapters, multiple O-rings can be used to ensure a sealing engagement between the mating ports. However, multiple spatially arranged O-rings can exhibit relatively low alignment tolerances when multiple pneumatic ports 240 are inserted into corresponding adapter ports. In addition to tolerance issues, multiple O-ring connections can result in higher than desired engagement / disengagement forces between the cassette assembly 226 and its associated adapter. In another configuration, a wiper gasket web can be used to form the necessary seal and can be attached between two interacting plates or blocks of the adapter. Figure 53 shows an exemplary wiper gasket 284 that can be molded as a single unit, thereby substantially simplifying assembly and installation procedures. Figure 54 shows an exemplary wiper gasket used in one of the manifold adapters. Figure 55 shows a cross-sectional view of the wiper gasket of Figure 54 taken along line 33H-33H. As shown, gasket 284 may be formed to annularly surround port 285 and form a conical peripheral recess toward pneumatic port 285. Gasket 284 may optionally include an annular nodule or ridge 283 built into wiper gasket 284 to cover a portion of port 285. This configuration and structure of wiper gasket 284 may allow insertion of cassette port 240 with an acceptable amount of force and may also ensure a seal between the adapter and cassette during operation (i.e., during application of positive and negative pressure through the adapter's port).

[0097] 56 and 57 show a cassette seating device or cassette loader 292 used to secure a first side of cassette assembly 226 for linear movement of the cassette assembly toward or away from one or more arrays of receptacle assemblies arranged to mate with corresponding arrays of cassette ports 240 on one or more of cassettes 228, 230, and 232 on an opposing second side of cassette assembly 226. In the example described below, the receptacle assemblies include manifold adapters 266, 268, 270, although the cassette loader could be used in any other system in which ported cassettes are inserted into and removed from any type of receptacle array, including, among others, a fixed multi-port receptacle, or a movable connector with an array of ports. The receptacle ports to which the cassette actuation ports connect could also be located directly on the frame, housing, or manifold output port array rather than on the exemplary adapters 266, 268, 270 shown, if the two sets of mating ports could be positioned so that they are properly aligned. The cassette seating device 292 has general utility in assisting a cassette having external ports to engage or disengage with a mating connector or receptacle port on any device.

[0098] Figure 56 shows cassette loader 292 in a stowed position, moving a cassette assembly linearly away from receptacle port 261b of Figure 29, or ports 266P, 268P, and 270P of Figures 30, 32, and 45, or more generally, port 271 of Figure 52, which in this example is arranged on adapters 266, 268, and 270. It should be noted that cassette seating device or cassette loader 292 can be used to seat or disengage cassettes or cassette assemblies in or from receptacle assemblies, so long as a single cassette or group of cassettes has either a fluid port or an actuation port on the side opposite that secured by cassette seating device 292.

[0099] In this example, cassette seating device 292 includes a fixed frame 294 that includes fixed members 296 a,b. Fixed members 296 a,b are coupled to a linkage that interacts with a movable cassette mount 298. Movable cassette mount 298 is configured to hold a cassette or cassette assembly, and in this example includes flanges 300 a,b that connect to cassette mount rails 302 a,b. In this example, cassette mount rails 300 a,b allow the cassette or cassette assembly to be slidably held in place on seating device 292. Other examples include a clamping device that can grip the cassette or cassette assembly. In this example, independent movement of the mounted cassette or cassette assembly is limited by the presence of one or more cross members 304 that limit movement of the top side of the mounted cassette or cassette assembly, and by actuator arms 306 a,b on operating handle 308 that move to a position that prevents lateral movement of the mounted cassette or cassette assembly.

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

[0101] To help ensure linear movement of the cassette mount 298, one or more guide elements (e.g., posts 322, etc.) can be optionally included to limit lateral movement of the cassette mount 298 and its attached mounting rails 302 a, b. The guide elements 322 can be rigidly attached or mounted to the fixed frame 294 (or alternatively to the fixed members 296 a, b) and extend in the desired direction of movement of the cassette mount rails 302 a, b. The guide elements 322 can interact with the cassette mount 298 (or alternatively to the flanges 300 a or 300 b, or the mounting rails 302 a, 302 b) via guide holes 324 (or guide rails, tracks, or other elements) that limit forward and backward movement of the cassette mount 298 relative to the frame 294 or fixed members 296 a, b.

[0102] FIG. 56 shows the cassette seating device 292 in a nearly fully retracted position, with the cassette mount 298 retracted far enough away from the associated receptacle assembly to disengage the cassette actuation (or fluid) ports of an attached cassette from their respective receptacle ports (see, e.g., FIGS. 30 and 31). FIGS. 57-59 show the cassette seating device 292 in an engaged position, with the cassette mount extended linearly away from the stationary frame 294 or stationary members 296a, 296b far enough to engage the cassette actuation (or fluid) ports of an attached cassette with their corresponding receptacle ports. Actuator arms 306a, 306b of the handle 308 are pivotally connected to the stationary members 296a, 306b at their distal ends 326. Each actuator arm 306a, 306b is also pivotally connected to a first end of a connecting member 330a, 330b at a more proximal portion 328 of the arm 306a, 306b. The second ends of connecting members 330a,b are in turn pivotally connected to an actuator bar 332 which has a pivot connection to the second end of each swing arm 310a,b which comprises the linkage of cassette seating arrangement 292. Connecting member 330a or 330b moves eccentrically relative to the axis of rotation of actuator arm 306a or 306b, thereby displacing actuator bar 332a,b and swing arms 310a,b away from fixed members 296a, 296b.

[0103] Optionally, a cassette mount retaining member 334 can be used to retain the cassette mount 298 in the retracted position. In one example, the cassette mount retaining member 298 may include a pawl that is displaced 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 to the retracted position (see FIG. 56 ). When the cross member 304 reaches the pawl recess 336, the pawl descends to engage the cross member 304 and retain the cassette mount 298 in its retracted position. In additional or alternative embodiments, the handle 308 may include a movable plunger element (instead of the handle post 338 (see FIGS. 57 and 59 )) that can engage or penetrate a hole or recess (not shown) in a forward flange 340 of the stationary frame 294. Optionally, the plunger may be spring loaded to automatically engage the forward 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 interior ceiling of the enclosure 254, as shown in FIGS. 45 and 46. It is located opposite the receptacle assemblies 266, 268, 270 (in this case, the manifold adapters). The cassette assembly 226 can be seen mounted to the cassette seating device 292 by a cassette assembly frame plate 513, as shown in FIGS. 21 and 46, for example. In FIGS. 30 and 31, the cassette assembly port 240 is shown 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 the retracted position (FIG. 30).

[0105] Pneumatic pump system using binary valves Figure 60 is a schematic diagram illustrating one embodiment of a pressure actuation system 14000 for a positive displacement diaphragm pump ("pod pump") 234 as shown in Figure 20. In this example, air pressure is used as the control fluid (e.g., so that the pump is pneumatically driven). In other embodiments, other fluids (e.g., water or water-based solutions) may also be used as the control fluid.

[0106] In FIG. 60, a pressure actuation system 14000 alternately supplies positive and negative gas pressures to the actuation chamber 14020 of the pod pump 23a. The pneumatic actuation system 14000 includes an actuation chamber pressure transducer 14020, a positive supply valve LP1, a negative supply valve N1, a positive pressure gas source LPOS, a negative pressure gas source NEG, a positive pressure source pressure transducer (not shown), a negative pressure source pressure transducer (not shown), and an electronic controller 14035. The electronic controller receives pressure data from the pressure sensor 14020 and controls the valves N1 and 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 two separate valves LP1 and 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] Positive pressure source LPOS supplies a positive pressure control gas to actuation chamber 14020 to urge diaphragm 14025 toward a position that minimizes the volume of pumping chamber 14027 (i.e., a position where the diaphragm abuts the rigid wall of the pumping chamber). Negative pressure source NEG supplies a negative pressure control gas to actuation chamber 14020 to urge diaphragm 14025 in the opposite direction toward a position that maximizes the volume of pumping chamber 14027 (i.e., a position where the diaphragm faces the rigid wall of the actuation chamber).

[0108] The controller 14035 may also receive pressure information from three other pressure transducers: the actuation chamber pressure transducer 14020, the transducer on the LPOS, and the transducer on the NEG. As their names suggest, these transducers measure the pressure in the actuation chamber 14020, the positive pressure source LPOS, and the negative pressure source NEG, respectively. The controller 14035 monitors the pressure in the two pressure sources LPOS, NEG to ensure they are properly pressurized (either positively or negatively). A compressor-type pump may be used to maintain the desired pressure in the reservoir containing the LPOS, NEG pressure sources.

[0109] In one embodiment, the pressure supplied by the positive pressure reservoir LPOS is sufficient under normal conditions 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 sufficient under normal conditions to fully bias the diaphragm against the rigid wall of the actuation chamber. However, in preferred embodiments, the positive and negative pressures supplied by the pressure sources LPOS, NEG are kept within safety limits sufficient to avoid excessively high fluid pressures that could be harmful to a patient to whom the pump system may be connected.

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

[0111] The pressure actuation system includes 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 extend through the manifold. The manifold may be configured to fit completely or mostly into the recess 258 of the hemodialysis housing (see, e.g., FIGS. 44 and 48). In this configuration, components that come into contact with the blood or dialysate (i.e., the pod pump 23a, the inlet valve 192, and the outlet valve 193) may be located within an insulated enclosure 254 or front panel 248 (see FIG. 23) so that the pumps, valves, and interconnecting fluid pathways can be more easily accessed and / or sterilized.

[0112] Pumping Process with Binary Valves 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 actual pressure 14055 measured by the pressure sensor 196 (FIG. 60) are plotted against time for one pump stroke and one fill stroke. The pump stroke involves using positive pressure from the LPOS source to drive the diaphragm 14025 from one side of the pump pod 23a to the other, displacing liquid within the pumping chamber 14027. In contrast, the fill stroke uses subatmospheric pressure from the NEG source to pull the diaphragm 14025 back across the pod pump 23a, filling the pod pump with liquid. In some examples, the fill stroke is completed by connecting the actuation chamber 14020 to atmosphere, allowing 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 fill pump strokes involve multiple charge cycles, producing the jagged pressure trace 14050 of FIGS. 61 and 62. The beginning of the delivery stroke is shown in detail in FIG. 62. In this figure, during liquid transfer, the actual pressure 14055 increases when valve LP1 is open and decreases when valve LP1 is closed. During the delivery stroke, the movement of liquid from the pumping chamber 14027 decreases the volume of the pumping chamber, and since the total volume of the pod pump is fixed, this increases the volume of the actuation chamber 14020. As the volume of the actuation chamber increases, the pressure in the actuation chamber decreases when 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. Three complete charge cycles are shown, each with a different duration. Figure 62 plots details of the pumping stroke with positive pressure applied. Referring now to the filling stroke relative to Figure 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, exposing the actuation chamber to the NEG pressure source, and then slowly recovers toward atmospheric pressure when the N1 valve is closed. Again, the charge cycle includes a rapid increase in the magnitude of the actuation chamber pressure, followed by a slower pressure decay to atmospheric pressure when the N1 valve is closed.

[0114] While in previous applications and disclosures, continuously variable valves have been used to control diaphragm pumps, this specification describes binary valves that are either fully open or fully closed, and are not designed to be partially open. Binary valves and associated control electronics are generally less expensive than variable-open valves. Additionally, binary valves may require fewer function checks / monitoring and may be less sensitive to the presence of waste products in the pneumatic passages leading to or leaving them. The digital or on / off functions inherent in binary valves require unique control algorithms for pressure control, end-of-stroke detection, and flow path occlusion.

[0115] The controller 14035 controls the valves N1 and LP1 according to several algorithms that may be executed sequentially or simultaneously based on signals received from the pressure sensor or transducer 196. These control algorithms are typical of binary valves due to their inherent digital or on / off functionality. The control algorithms include an algorithm to control fluid flow rate through the pump, an algorithm to control pressure in the actuation chamber 14020, an algorithm to detect an end-of-stroke (EOS) condition, an algorithm to detect complete occlusion of the inlet line, an algorithm to detect complete occlusion of the outlet line, an algorithm to detect partial occlusion, and an algorithm to measure access metrics (an indicator of the quality of blood flow obtained from the patient's venous or fistula access).

[0116] The controller 14035 calculates information regarding the flow of fluid through the pump based on the pressure signal from the sensor 196 when the valves N1 and LP1 are closed. The controller 14035 uses the received pressure data to control the actuation chamber pressure, detect EOS, occlusions, and partial occlusions, and determine access metrics.

[0117] Pressure Control Description The flow rate through a pneumatically actuated diaphragm pump, such as pod pump 23a, is controlled by setting a target pressure for the actuation chamber 14020. The pod controller 14035 then controls the pressure in the actuation chamber 14020, as measured by a pressure sensor 196 fluidly connected to the actuation chamber 14020, by controlling valves N1, LP1, which fluidly connect a pressure source to the pump's actuation chamber. In an exemplary control algorithm, the controller averages pressure data from the pressure sensor 196 while the binary valves N1, LP1 are closed and opens the valves N1, LP1 when the cumulative average pressure approaches or equals the target pressure. In one example, the controller 14035 closes the valves N1, LP1 when the magnitude of the pressure data is equal to or greater than the target pressure. In one example, the controller 14035 closes the valves N1, LP1 when the magnitude of the pressure data is equal to or greater than the target pressure minus a predetermined constant. In another example, the predetermined value is not constant but varies with the direction of stroke and the duration or phase of the stroke. In another example, the controller 14035 integrates the magnitude difference between the measured pressure and the target pressure and opens valves N1, LP1 when the integrated difference approaches or equals zero.

[0118] Fluid flow through the pump is controlled by the magnitude of the negative pressure applied to the actuation chamber to fill the pumping chamber with liquid and the magnitude of the positive pressure applied to the actuation chamber to pump liquid out of 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 of the pod pump 23a. The controller 14035 may set an initial target pressure for the fill and pump strokes. The controller controls the pressure in the actuation chamber to reach or approach the target pressure. The controller monitors the time to complete the stroke and determines the actual flow rate by dividing the displacement by the time to complete the stroke. The controller 14035 may modify the target pressure based on the difference between the most recent actual flow rate and the desired flow rate. For example, the controller 14035 may increase the target pressure if the measured actual flow rate falls below the desired flow rate. In another example, the controller may decrease the target pressure if the measured actual flow rate exceeds the desired flow rate. The controller 14035 may modify the pump stroke independently of the fill stroke. In one example, the controller 14035 may use a feedback loop to modify the delivery target pressure based on the measured flow rate during the delivery stroke to achieve the desired flow rate. In another example, the feedback loop modifies the negative fill target pressure based on the measured flow rate during the fill stroke to achieve the desired fill rate.

[0119] In previous disclosures, a chamber connected to a pressure source by a binary valve was controlled based on a limit relative to a target pressure. The controller connected the pressure source to the chamber by opening the valve when the measured pressure in the chamber was lower than the target pressure by a predetermined amount. The controller then closed the valve when the measured pressure in the chamber exceeded the target pressure by a second predetermined value. In some cases, applying this limiting approach to a pneumatic diaphragm pump produced an average chamber pressure lower than the target pressure. In some cases, opening the valve caused the pressure in the chamber to increase very rapidly, while the pressure decrease due to fluid flowing in and out of the pumping chamber was much slower. This discrepancy in the rate of pressure change biased the time-averaged pressure lower than the target pressure. If the flow of fluid in and out of the pump changed over time, the offset between the average pressure and the target pressure also changed over time, making it difficult to continuously correct for the discrepancy in the rate of pressure change.

[0120] The pressure in the actuation chamber can be controlled by comparing the measured pressure to a target pressure. The controller opens and closes a pneumatic valve connecting the actuation chamber to a pressure source or reservoir. The controller can open and close valve LP1 during a delivery stroke to maintain the pressure in the actuation chamber 14030 near a delivery target pressure 14052. The controller 14035 opens and closes valve N1 during a fill stroke to maintain the pressure in the actuation chamber 14030 near a fill target pressure 14054. In one example, the controller closes the pneumatic valve when the magnitude of the measured pressure exceeds the target pressure and reopens the pneumatic valve when the average measured pressure in the actuation chamber approaches or equals the target pressure.

[0121] In the algorithm shown in Figures 63 and 64, as described below with reference to Figure 62, the controller 14035 controls the valves N1, LP1 to hold the average pressure in the actuation chamber 14020 at the target pressure by maintaining the average pressure in the actuation chamber at the target pressure while the valves N1, LP1 are closed. Referring now to the pressure control algorithm 14100 in Figure 63 and with reference to Figure 60, the pump controller (which may be separate or distinct from the controller 14035 in Figure 60) selects a stroke direction 14105 and target pressure, fill and PTF (pressure-target-fill), or deliver and PTD (pressure-target-delivery). If a fill stroke is selected, the controller 14035 opens the valve fluidly connecting the NEG pressure source or reservoir to the actuation chamber 14020 at 14110 and monitors the pressure sensor 196 at 14120. At each time step in block 14130, the controller evaluates whether the pressure magnitude is greater than the target pressure magnitude; if not, it leaves the valve open. At block 14140, if the measured pressure magnitude is greater than or equal to the target pressure, the N1 valve is closed. At block 14150, the difference between the measured pressure P and the target pressure TTF is summed at each time step. At block 14160, an end-of-stroke function or algorithm checks for end-of-stroke and, if the EOS criteria are met, transitions the controller logic to end-of-stroke 14200. Note that the logic at block 14160 may be located anywhere between 14140 and 14180 in the flowchart, or may be a separate function from the pressure control algorithm 14100. At 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 an additional time step. If the sum of the pressure differences is less than or equal to zero, the controller logic sets the sum of the pressure differences to zero at block 14180 and returns the logic to block 14110 where the N1 valve is opened.

[0122] A single controller can coordinate the timing of pump strokes, setting of target pressure, and operation of the air pressure control valve. Alternatively, tasks can be divided among two or more controllers. For example, a main controller determines the timing of pump strokes and target pressure, while a sub-controller controls the air pressure control valve. Referring to FIG. 63 and FIG. 60, when the main controller selects a pump stroke, the main controller also defines the target pressure, and the sub-controller transfers the logic to block 14210 (FIG. 63), where the LP1 valve is opened. In a series of steps similar to the fill process, the pressure in the actuation chamber 14020 is monitored by the pressure sensor 196 in block 14220. Block 14230 evaluates the pressure against the target pressure, and if the measured pressure is equal to or greater than the target pressure, the logic transfers to block 14240, where the LP1 valve is closed. Referring now to FIG. 60, after the LP1 valve is commanded to close in 14051, the chamber pressure 14055 continues to increase until the chamber pressure exceeds the target pressure. Chamber pressure 14055 may increase to 14052 due to delays in valve closure and due to fluid / thermodynamics that may affect 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. This sum of the differences between the chamber pressure P and the target pressure PTD from point 14052 until the chamber pressure 14055 equals the target pressure 14050 is area 14080 in FIG. 62. Area 14085 is the sum of the differences 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, the EOS algorithm is executed in block 14260, and if an EOS is detected, the process ends at 14200.

[0124] At block 14270, the sum of the pressure differences from block 14250 is evaluated. Block 14270, if the sum of the pressure differences is less than or equal to zero, moves the logic to 14210 where the LP1 valve is again opened. Before the logic reaches block 14210, the sum of the pressure differences is set to zero at block 14280, at which point LP1 is opened. Alternatively, the sum of the pressure differences may be zeroed any time in the logic after block 14270 and before block 14240.

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

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

[0127] Because the delay in valve actuation is a fixed value and the pressure overshoot is inversely proportional to the volume of the actuation chamber (which varies during the stroke), the overshoot also varies, as can be observed in FIG. 61. Generally, the overshoot is greatest at the beginning of the delivery stroke 14060 and at the end of the fill stroke 14075, when the volume of the actuation chamber 14020 has its smallest volume. The offset for the fill stroke and the delivery stroke may vary during the stroke. In one example, the magnitude of the offset is greatest at the beginning of the delivery stroke and decreases with each charge cycle until the offset reaches a minimum value. In the same example or another example, the magnitude of the offset is smallest at the beginning of the fill stroke and increases with each charge cycle until the offset reaches a maximum value. The offset value may vary with time, number of charge cycles, valve openings, or the total pressure differential when the valve is closed during the stroke.

[0128] Another example of a pressure control algorithm 14300 is shown in FIG. 64. Algorithm 14300 is similar to algorithm 14100, except for elements 14350, 14370, 14380, 14450, 14470, and 14480, where the difference between the measured pressure and the target pressure is replaced with an average pressure. In blocks 14350 and 14450, the measurements of pressure sensor 196 are averaged while valves N1 and LP1 are closed. In blocks 14370 and 14470, if the average pressure, PAVG, is equal to the target pressure within some predetermined margin, the logic zeros the average pressure before proceeding to blocks 14110 and 14210, respectively, to open valves N1 and LP1.

[0129] End of journey detection Accurate or reliable determination of the flow rate and volume through the pump 23a, as shown in FIG. 60, depends on an accurate or reliable algorithm for determining end-of-stroke (EOS). End-of-stroke occurs when the diaphragm 14025 moves across the pump body cavity and reaches one of the pump body walls. The controller 14035 detects the chamber pressure relative to the wall by observing that the magnitude of the chamber pressure measured by the pressure sensor 196 does not decrease when the valves N1 and LP1 are closed. Because the diaphragm 14025 is unable to move against the chamber wall and therefore cannot change the volume of the actuation chamber 14020, the chamber pressure does not decrease.

[0130] The EOS detection algorithm detects an end-of-stroke condition based on the state of the valve, the chamber pressure, and the rate of change of the chamber pressure. This algorithm detects an EOS condition for an air-operated diaphragm pump. In this case, the air pressure is controlled by a pneumatic valve connecting the pump to a pressure reservoir, a pressure sensor measuring the air 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 occur and the rate of change of the pressure magnitude is less than a predetermined rate. In another example, EOS is declared when a predetermined number of charge cycles occur, the pressure is within a predetermined range, and the rate of change of the pressure magnitude is less than a predetermined rate.

[0131] Referring now to FIG. 60, the controller 14035 changes the stroke direction from delivery to filling or from filling to delivery after detecting the end of stroke (EOS). The end of stroke algorithm is shown schematically 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 algorithms may be executed in parallel. Block 14310 monitors the pressure in the actuation chamber as sensed by the pressure sensor 196 (FIG. 60). In block 14320, the number of charge cycles that have 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 pressure magnitude (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 P is evaluated. If the difference is less than a predetermined difference DP, EOS is declared and the controller changes the pump stroke, target pressure, and switches the state of the hydraulic valves 192, 193. (The valves in the dialysis systems described herein can be diaphragm valves that can also be actuated by pressure supplied by a manifold and controlled by the controller.) If the difference between the chamber pressure and the target pressure is greater than a predetermined difference, the controller 14035 declares an occlusion.

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

[0133] Occlusion Detection 60, the controller 14035 can be configured to detect occlusions in the flow into or out of the pump 23a. The user interface can provide an alert or alarm that the inlet or outlet line is occluded. In one example, the user can instruct the blood lines 203 and 204 to be inspected for kinks, pinches, or other occlusions. The occlusion detection algorithm can be considered a safety feature to prevent thrombosis in the blood circuit or can identify fluid flow problems in the water or 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 actuation chamber 14020 is isolated from the pressure reservoirs NEG and LPOS. The pressure sensor 196 measures the pressure in the actuation chamber. The controller 14035 detects blockages in the inlet line during the fill stroke and blockages in the outlet line during the pump stroke. The controller 14035 sums the pressure changes occurring in the actuation chamber while the N1 and LP1 valves 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 with the sum of the pressure differences during the previous stroke and a predetermined value. The controller 14035 may also detect a blockage based on the number of charge cycles completed before the end of the stroke is detected and / or the difference between the actuation chamber pressure and the target pressure.

[0135] Referring now to FIG. 66, the occlusion algorithm 14400 is shown as a flowchart beginning in step 14410, where either a fill stroke or a pump stroke is initiated by setting a target pressure and then opening valves N1, LP1 (FIG. 60) in step 14415. Valves N1, LP1 are closed in step 14420. In step 14425, the controller sums the pressure change while pneumatic valves N1, LP1 are closed (dPSUM). The sum of the pressure change (dPSUM) is summed over the entire stroke, which includes multiple 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 pneumatic valves N1, LP1 are closed, it calculates Pi-1-Pi and adds this pressure change to the running sum of the pressure change. In one example, the controller determines the pressure change between when valves N1, LP1 close and when they open again, and then adds this pressure change to a total pressure change (dPSUM) that includes all pressure changes since the stroke began in step 14410.

[0136] Continuing with reference to FIG. 66, the closure algorithm 14400, after updating the pressure change sum (dPSUM) in step 14425, checks for an end-of-stroke condition in step 14430. If EOS is not detected, the controller 14035 checks to see if the charge cycle is complete and it is time to reopen the valves in step 14435. 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 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 pressure change sum is updated for the next time step in step 14435. Once the charge cycle is complete, the pneumatic valves N1, LP1 are reopened in step 14415.

[0137] Once the end of stroke is determined in step 14430, the occlusion algorithm 14400 transitions to multiple independent occlusion tests in steps 14440, 14450, 14455, and 14460. Step 14440 transitions the logic to a low-sensitivity step 14450 and a high-sensitivity step 14445. In one example, step 14440 selects low sensitivity for a short or partial stroke of the blood pump due to the variability of short strokes within the blood pump. In a short stroke, the diaphragm is not driven against the inner wall of the pod pump. Instead, the delivery stroke is shortened. In some medical applications, a short delivery stroke may be beneficial to reduce damage to blood cells between the diaphragm 14025 and the wall of the pod pump 23a. A short stroke has greater variability, and a low-sensitivity occlusion test in step 14450 may be recommended to avoid false occlusion detection. In one example, step 14440 transitions the logic to step 14445 for all non-short stroke operations.

[0138] Continuing to refer to FIG. 66, the occlusion algorithm 14400, in step 14445, compares the sum of the pressure differences during the just-completed stroke (dPSUM) to the sum of the pressure differences for the last good stroke in the same direction (dPGOOD). In one example, an occlusion is detected when two consecutive strokes in the same direction have dPSUM that is less than 30% of the last good stroke (dPsum). More generally, an occlusion is detected when a stroke has a dPSUM that is less than a predetermined percentage of the last good stroke (dPsum). In one example, an occlusion is detected when three or more strokes have a dPSUM that is less than a predetermined percentage of the last good stroke (dPsum). If an 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 no occlusion is detected at 14445, the logic moves to step 14455.

[0139] FIG. 66 shows an overview of the occlusion algorithm 14400, which includes a low sensitivity step 14450 comparing the sum of the pressure differences during the just-completed stroke (dPSUM) with the sum of the pressure differences for the last good stroke in the same direction (dPGOOD). In one example, an 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, an occlusion is detected when one stroke has a dPSUM that is less than a second predetermined percentage of the last good stroke (dPsum). Alternatively, an occlusion is detected when four or more strokes have a dPSUM that is less than a predetermined percentage of the last good stroke (dPsum). If an 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 in 14450, the logic proceeds to step 14455.

[0140] In step 14455, the controller 14035 detects an occlusion if either of the following conditions occur: fewer than a predetermined number of charge cycles occur in one or more consecutive strokes in the same direction; or the sum of the pressure changes (dPsum) is less than a predetermined limit (dPsum_limit). In one example, an occlusion is detected if either condition occurs in three consecutive strokes in the same direction. In another example, an occlusion occurs if either condition occurs in two consecutive cycles. In another example, the predetermined number of charge cycles is five. In another example, the predetermined number of charge cycles is half the number of charge cycles in a typical stroke. If an occlusion is detected, the logic proceeds to step 14470, where an occlusion alert or alarm is sent to the user interface (UI). One exemplary response is to stop the pump. The controller may send data to the UI indicating which pump is affected and whether the occlusion occurred in the inlet or outlet line. If an occlusion is not detected in 14455, the logic proceeds to step 14460.

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

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

[0143] Blood Flow Metrics In one embodiment, the controller can be programmed to provide a user of the extracorporeal or hemodialysis system with an indication of blood flow metrics (the quality or rate of blood flow from the venous access or arteriovenous fistula) during the course of each pump's fill stroke. For example, flow metric values ​​can be transmitted to a graphical user interface, providing the user with a continuous indication of the quality or adequacy of blood flow in the blood line during treatment. 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 proportionally scaled to a range of 1 to 5, with a value of "5" representing, for example, excellent flow, a value of "3" representing marginal flow, and a value of "1" representing obstructed flow. Thus, a specified range of flow metric values ​​can be mapped to each of the set values ​​from "1" to "5" to simplify the user's interpretation of the adequacy of blood flow in the blood line. In other embodiments, the flow metric can be displayed graphically to the user, such as, for example, a moving or expanding bar graph, a dial gauge, or a set of colored lights.

[0144] In a preferred embodiment, a marginal or suboptimal flow metric may cause the controller to issue an alert to the user so that the user can attempt to improve blood flow in the blood line (e.g., repositioning the line, straightening the line, adjusting the vascular access cannula, etc.). The controller may be programmed to initiate a procedure to pause or stop the dialysate pump, including signaling the user to allow sufficient time to lapse before pausing or stopping the dialysate pump, so that the user can correct the condition. The user may be alerted to a low-flow condition during the fill stroke, allowing timely adjustment by the user to restore the flow metric to an acceptable value before the fill stroke ends. Alternatively, the controller may be programmed to allow suboptimal flow metric values ​​for two or three (or more) consecutive fill strokes before commanding the dialysate pump to stop. Thus, timely correction of the low-flow condition by the user may avoid interruptions in dialysate pumping and, in some cases, treatment. In one example, the controller may be programmed to pause or stop the dialysate pump if the flow metric remains below 150 (e.g., as dP / dt in mmHg / sec) for three consecutive fill strokes, and not restart the dialysate pump until the flow metric exceeds 200 for five consecutive blood pump strokes. In some of these embodiments, the controller allows the blood pump to continue operating while the dialysate pump is stopped, so that the user has an opportunity to restore blood flow conditions that allow the dialysate pump to be restarted, thereby avoiding premature termination of therapy.

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

[0146] FIG. 67 illustrates the flow metric algorithm 14500 as a flowchart beginning with "Start of fill stroke" using the blood pump (23a in FIG. 60). The upstream valve 192 is opened and the downstream valve 193 is closed. The fill stroke continues by opening the pneumatic valve N1 in step 14515 and closing the valve N1 in step 14520 to generate a desired negative pressure or a pressure below 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 tubing 203 and into the pumping chamber of the blood pump 23a. The magnitude of the negative pressure in the working chamber 14020 decreases as the fill 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 communicated to the controller 14035 in step 14525 (FIG. 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 actuation chamber in step 14530. If the end of the charge cycle has occurred, step 14535 transitions the logic to step 14540 where the end of stroke (EOS) is determined. If the end of the charge cycle has not occurred, the logic transitions to 14525, where the pressure signal continues to be monitored. If an EOS is not detected in step 14540, the controller determines the minimum magnitude of dP / dt during which valve N1 is closed in step 14545. The minimum or lowest dP / dt of the current charge cycle detected by the controller is then used in the LPF to update the minimum dP / dt for the fill stroke in step 14550, and valve N1 is reopened to begin the next charge cycle in step 14515. If EOS is detected in step 14540, the logic moves to step 14555 where the pod controller 14035 reports the minimum dP / dt to the controller, which converts the minimum dP / dt value into a more easily understood indicator that is displayed on the user interface (UI).The UI can be a graphical display unit such as a tablet computer. The indicators are flow metrics for 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 occluded access, 3 is marginal access, and 5 is free-flowing access. Here, access refers to the needle or cannula system, needle or cannula placement, and restriction of flow at the inlet to the needle or cannula. In one example, the flow metric is 1 for a minimum dP / dt of less than 25 mmHg / s, or occluded; 2 for a minimum dP / dt of 25-50 mmHg / s, or poor; 3 for a minimum dP / dt of 50-75 mmHg / s, or marginal; 4 for a minimum dP / dt of 75-100 mmHg / s, or good; and 5 for a minimum dP / dt of 100-125 mmHg / s, or excellent. In addition to displaying the flow metric on the UI in step 14555, the flow metric algorithm 14500 in step 14560 evaluates the flow metric and issues an alert to the user 14570 if the flow metric remains below a predetermined value for more than a predetermined number of strokes or time period. In one example, step 14560 issues an alert in step 14570 if three consecutive fill strokes have a dP / dt below a value of 50 mmHg / sec. In this case, regardless of the flow metric or minimum dP / dt, the logic proceeds to the delivery stroke of the blood pump in step 14580 and then returns to begin the fill stroke in step 14510.

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

[0148] The HDD controller can be configured to send a start signal to the WPD, representing a command to begin generating warm water, and the WPD proceeds according to its independently programmed processor. This is the mode typically used when delivering purified water to the HDD for dialysate mixing and treatment. The HDD controller can also send a start hot water command to the WPD, representing a command to begin generating hot water according to the WPD's pre-programmed process. This is the mode typically used to perform a WPD sterilization procedure. The lines connecting the WPD and HDD (the HDD's water supply lines) 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 a standby mode or state, or an idle mode or state. In a water vapor compression / distillation device, an idle state may include pausing the pump or compressor, turning off the heater, closing the valves, and deactivating the control loop and water level controller. A standby mode or state allows the WPD to produce purified water relatively quickly. Optionally, in a steam / distillation system, this may include filling the purified water system with water, heating the water to a point where purified water production can begin, controlling a vent valve to maintain a low-pressure steam temperature target, and, optionally, producing enough water to fill a reservoir, or alternatively, draining any excess water that is produced. When the WPD is starting from an inactive (off) state or idle state, the HDD controller can optionally be programmed to send a command early enough to allow the WPD to produce water by the time the HDD expects to receive water (in some cases, this may be as little as two hours from a cold start or start from idle mode, or as little as about ten minutes from standby mode). In most cases, the HDD controller will command an idle WPD to go into standby mode when the two systems establish communication, or when one or both systems are powered off and then restarted, which cannot happen if an error condition is flagged.

[0150] During water supply, the HDD controller can send a stop signal to the WPD, instructing the WPD to enter a standby state. In this case, the standby state is an autonomous function of the WPD that keeps water production or purification active enough so that it can dispense water as directed by the HDD within a relatively short period of time (e.g., within about 10 minutes of a start or resume command being sent from the HDD to the WPD). Among other processes, this can include filling the water purification system with water and heating the water to a point where purified water production can begin quickly.

[0151] The HDD controller can also send a sterilization start command to the WPD, typically scheduled for completion of a dialysis treatment or during the time between treatment sessions with the HDD. In this case, the WPD enters automatic hot water generation mode. In a typical sequence, the HDD first instructs the WPD to transition to water generation mode, and then, upon receiving notification that the WPD has entered water generation mode, instructs it to transition to sterilization mode. When the water generated by the WPD reaches a predetermined temperature (e.g., 90 degrees Celsius), a signal is transmitted to the HDD controller, causing the HDD to initiate a sterilization procedure for the inlet line. The inlet line includes the flow path within the HDD before the branch point connects the HDD to the drain or flow path to the HDD's mixing circuit (beyond this branch point, the HDD's internal flow path can be sterilized by a programmed circulation of hot water or chemical sterilants without a "closed end"). In this state, all tubing connecting the WPD's output port or output line to the HDD's input port or input line is also sterilized.

[0152] The HDD controller can be programmed to sterilize the WPD-HDD connection line and flow path at a predetermined minimum temperature for a predetermined minimum time. For example, the sterilization temperature can be set to 85°C for a minimum time of 35 minutes. The temperature can be measured by a temperature sensor located in the HDD water inlet line. To reduce the number of temperature sensors in the HDD system, an inlet water temperature sensor can also be preferably located in the HDD flow path at a location that can monitor the temperature of the sterilizing fluid circulating through the HDD flow path during sterilization of the HDD system. Depending on the distance the inlet water travels before reaching the temperature sensor, the minimum sterilization temperature can be optionally adjusted to account for heat loss before the water reaches the sensor.

[0153] FIG. 68 shows a schematic diagram of the fluid flow paths for the hemodialysis system described in the previous application. Section A represents the system's blood flow path, section B represents the dialysate balancing and dialyzer delivery section, section C represents the dialysate storage, heating, and ultrafiltration section, and section D represents the water inlet and dialysate mixing section. The water inlet line 400 is configured to connect to an external water source. In this embodiment, the water source includes a water purification device (WPD), such as a water vapor compression / distillation device. For ease of reference, the water inlet line 400 is herein meant to represent 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 HDD's internal flow path. In practice, this inter-device water line may include one or more connectors or valves. However, for sterilization purposes, the water inlet line 400 can be considered to include the entire inter-device water line.

[0154] While the internal fluid flow paths of the WPD and the illustrated HDD can be configured to achieve a thorough and complete sterilization process, special care must be taken to sterilize the water inlet line and / or inter-device lines connecting the WPD to the HDD. Note that the water inlet line 400 has a valve connection 402 to the HDD internal flow paths, and this inter-device fluid connection (the WPD outlet line and the HDD inlet line) is closed-ended for the purpose of thorough sterilization, either chemical or thermal. This condition is also reflected in the WPD's outlet line. While an HDD dialysate heater can be used to heat water pumped by one or more dialysate pumps in the reverse direction to the HDD inlet line, the WPD outlet line, and the WPD's drain connection, it may be more efficient for purified hot water (or water containing an appropriate chemical sterilant) to be produced by the WPD and pumped in the normal forward direction to the HDD, with the sterilizing solution being discharged into the HDD's drain line 404.

[0155] FIG. 69 shows an isolated view of section D of the HDD system's flow path. A temperature sensor can be placed in line 400, but functions only to monitor the temperature of the incoming water. For sterilization purposes, the incoming heated water can be routed directly to drain 404, but this flow path relies on the operation of a water pump located within the WPD. Alternatively, temperature sensor 406 can be placed in internal line 408 connected to 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. Heated liquid from section C in FIG. 68 can be routed to the flow path in section D via water line 408. The inlet line disinfection flow path incorporating water pump 410 in the illustrated system of FIG. 69 (see also FIG. 68) is directed through conductivity / temperature sensors 412, 414 in the dialysate mixing path, and then bypasses dialysate tank 416 by closing valve 418 and opening valve 420, thereby directing to drain line 404. Note also that in alternative embodiments, monitoring of the temperature of the disinfectant solution can be accomplished using existing temperature sensors already installed for dialysate mixing purposes (i.e., sensor 412 or sensor 414) without adding a temperature sensor to water inlet line 400 or 408. In all of these cases, either actively managed valves or passive check valves ensure that the disinfectant solution is directed to drain line 404.

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

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

[0158] 71 , optionally, before initiating a sterilization counter for inter-device lines 400, the HDD controller begins controlling HDD internal pumps and associated valves to circulate heated water from the WPD for a predetermined period of time to completely fill the sterilization flow path with hot water (460). In addition to the inter-device lines, in one example, this flow path may include a flow path within the HDD that directs sterilized water through a water pump 410 in the mixing circuit via a line that leads to the dialysate tank 416 but is diverted to the drain 404 by one or more valves 418, 420 (see, e.g., FIG. 69 ). In one example, the HDD controller directs heated water from the WPD to the HDD drain for approximately two minutes before initiating the inter-device line sterilization counter.

[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 sensors 412 or 414), the controller starts a 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 sterilization of device-to-device line 400 complete. As long as the detected temperature remains at or above the minimum sterilization temperature, the sterilization timer is updated (464).

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

[0161] If sterilization of the inter-device lines 400 is successful (470), the HDD controller may close the water inlet line valve 402, instruct the WPD to initiate a sterilization procedure, and initiate the HDD sterilization procedure. If sterilization of the inter-device lines 400 is unsuccessful, the user is notified, and the WPD is instructed to pause water production (468). The HDD controller, under these circumstances, optionally initiates a repriming procedure for its flow paths and resets the sterilization timer to 472. The HDD controller may then wait for user input on whether to retry the sterilization procedure (474). If not, the HDD may optionally initiate a service call (476). The controller may be configured to provide appropriate instructions to the user on a user interface or automatically send appropriate messages to a remote server and service center via an internet communications 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 a filter within the system. This is typically performed after a filter change. If a filter (e.g., a carbon filter) change is indicated, the HDD controller first instructs the WPD to enter an idle state, then issues an alert to the user on the graphical user interface that the WPD is ready to change the filter. When the user indicates completion of this task, the HDD instructs the WPD to enter a standby state, then executes the flush mode. The HDD instructs the WPD to return to the standby state upon completion of this task, thereby enabling rapid initiation of water production at the start of treatment. The flush mode can also be instructed before fluid sampling to ensure a more reliable indication of filter quality. It may also be instructed if the WPD system has been in an idle or standby state for longer than a predetermined period of time.

[0163] Status messages may 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 may receive from the WPD may include:

[0164] -Current operating status of WPD -Identification code or identifier of the current WPD -Date the WPD filter was installed -Whether the filter needs to be replaced - Whether communication with WPD has been lost -Whether WPD shows any operational errors -Whether WPD indicates a failsafe error - Time since the WPD was last sterilized -Does the WPD need to be sterilized? -Software version installed on the WPD system controller The status message regarding the operational state of the WPD may include one or more of the following:

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

[0166] -WPD in standby; product valve open. -WPD produces room temperature water; product valve is open. -WPD is waiting for filter change; product valve is closed.

[0167] -WPD flushes lines and filters after filter change. -WPD produces hot water; once temperature is reached the product valve opens. -WPD performs sterilization; product valve is closed.

[0168] - The WPD produces 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 a water sample for testing.

[0169] -WPD is in fail-safe state; product valve is closed. Preferably, the HDD controller instructs the WPD to maintain standby mode whenever the WPD is not performing another process. If another process (e.g., sterilization) is in progress, the HDD controller waits for the process to complete. When the WPD enters standby mode, the HDD controller may check to see if the WPD should perform a filter flushing process. If so, the WPD starts the filter flushing process. Also, for example, if power is interrupted after a filter replacement before the filter flush is completed, the HDD may instruct the filter flushing process.

[0170] Optionally, before initiating treatment water production, the HDD may be programmed to require the user to sample the produced water from the WPD for various contaminants, such as chloramines. The HDD may instruct the WPD to enter a water sampling state. When the WPD indicates a ready to sample state, the HDD alerts the user to collect and test a water sample. If the user indicates that the sample passed the test, the HDD may instruct the WPD to begin treatment water production. If the user indicates that the sample failed the test, the HDD may optionally instruct the WPD to enter a standby state.

[0171] An error occurring from the WPD during water production can be notified to the HHD, which may then send instructions to acknowledge the error condition and alert the user via an interface (e.g., HDD interface). The WPD controller then awaits instructions from the user to resume water production or transition to a standby state. A fail-safe error condition typically stops WPD operation and signals the HDD to initiate a treatment termination procedure. The technical concepts that can be understood from the above-described embodiment will be described below as supplementary notes. [Supplementary Note 1] A manifold adapter configured to connect a pressure distribution manifold to a fluid processing cassette assembly, comprising: a housing having a first side including a first set of transfer ports configured to connect to the actuation output ports of the manifold, and an opposing second side including a second set of transfer ports configured to connect to the actuation input ports of the cassette assembly; the first set of transfer ports includes a first spatial array configured to match a spatial array of actuation output ports of a manifold; the second set of transfer ports includes a second spatial array configured to match a spatial array of actuation input ports of a cassette assembly; The manifold adapter, wherein the first spatial array of transfer ports is different from the second spatial array of transfer ports. [Appendix 2] A manifold adapter as described in Appendix 1, wherein the first spatial array covers an area of ​​the first side of the adapter housing having a first length and a first width, and the second spatial array covers an area of ​​the second side of the adapter housing having a second length and a second width, the second length being greater than the first length such that the housing of the manifold adapter overhangs the side of the manifold. [Appendix 3] The manifold adapter of Appendix 1, wherein the second side of the housing includes an elastomeric wiper gasket consisting of a plurality of wiper seals, each of the plurality of wiper seals associated with a transfer port on the second side of the adapter housing, and the wiper gasket is recessed under a top plate of the adapter housing. [Appendix 4] A seating device for a cassette having a plug-in side and an opposite mounting side, a stationary frame member connected to a movable cassette mount by a plurality of linkages on a first side of the cassette mount and an opposite second side of the cassette mount, the linkages on the first side of the cassette mount being connected to a first fixed flange of the stationary frame member and the linkages on the second side of the cassette mount being connected to a second fixed flange of the stationary frame member; each of the plurality of linkages includes a swing arm having a first end pivotally coupled to a fixed flange and a second end coupled to an elongated slot in the cassette mount; the second end of the swing arm is configured to move in an arcuate path to move the cassette mount; The elongated slot limits movement of the cassette mount by the swing arm to linear movement toward or away from the stationary frame member. [Appendix 5] The seating device described in Appendix 4, wherein the cassette mount includes a first movable flange and a first rail on the first side of the cassette mount and a second movable flange and a second rail on the second side of the cassette mount, each movable flange having a surface generally parallel to the direction of movement of the cassette mount, the elongated slot formed in the movable flange and oriented perpendicular to the direction of movement of the cassette mount, and the first and second rails hold a mounting side of a cassette. [Appendix 6] A seating device as described in Appendix 5, comprising a handle assembly pivotally connected to the cassette mount, wherein the cassette mount moves away from the fixed frame member when the handle of the handle assembly moves in a direction away from the fixed frame member, and the cassette mount moves towards the fixed frame member when the handle moves in a direction towards the fixed frame member. [Appendix 7] The seating device described in Appendix 6, wherein the pivot connections of the handle assembly include a first pivot connection of a first handle arm to the first fixed flange, a second pivot connection of a second handle arm to the second fixed flange, a third pivot connection of the first handle arm to a handle swing arm connected to the first movable flange of the cassette mount, and a fourth pivot connection of the second handle arm to a handle swing arm connected to the second movable flange of the cassette mount, and the first and third pivot connections and the second and fourth pivot connections are spaced apart from each other on the first and second handle arms. [Appendix 8] The seating device described in Appendix 6, including a third fixed flange of the fixed frame member, the third fixed flange facing the handle assembly and generally perpendicular to the first and second fixed flanges, the handle assembly including a spring-loaded plunger configured to engage a hole or recess in the third fixed flange so that the cassette mount is locked in a retracted position when a handle of the handle assembly is moved toward the fixed frame member. [Appendix 9] A method for controlling an air-operated diaphragm pump, comprising: opening a valve fluidly connecting a source of air pressure to an actuation chamber of the diaphragm pump; monitoring one or more pressures of gas within the working chamber of the diaphragm pump; closing the valve when the pressure in the working chamber is equal to or greater than a target pressure; and opening the valve when the average magnitude of the monitored pressure is less than the target pressure. [Appendix 10] The method of Appendices 9, further comprising averaging the pressure monitored after the valve is closed. [Appendix 11] The method of Appendices 10, further comprising setting the average pressure to zero before the valve is closed. [Appendix 12] The method of Appendices 9, wherein the valve is a binary valve. [Appendix 13] The method of Appendices 9, wherein the pressure is monitored by a controller having a pressure sensor fluidly connected to the actuation chamber. [Appendix 14] The method of Appendices 13, wherein the controller receives pressure information from the pressure sensor and controls the valve using the pressure information. [Appendix 15] A method for controlling a fluid flow rate of an air-operated diaphragm pump, comprising: initially opening a valve fluidly connecting a source of air pressure to an actuation chamber of the diaphragm pump; monitoring one or more pressures of gas within the working chamber of the diaphragm pump; marking the time of opening of the first valve; closing the valve when the pressure in the working chamber is equal to or greater than a target pressure; opening the valve when the average magnitude of the monitored pressure falls below the target pressure; detecting the end of a pump stroke based on the monitored pressure; marking the time of the end of the pump stroke; and varying the target pressure based on a difference between a stroke duration and a predetermined target stroke duration, the stroke duration being the difference in time between the end of the pump stroke and the opening of the first valve. [Appendix 16] The method of Appendices 15, further comprising averaging the pressure monitored after the valve is closed. [Appendix 17] The method of Appendices 16, further comprising the step of setting the average pressure to zero before the valve is closed. [Appendix 18] The method of Appendices 17, wherein the valve is a binary valve. [Supplementary Note 19] The method of Supplementary Note 15, wherein the pressure is monitored by a controller using a pressure sensor fluidly connected to the actuation chamber. [Supplementary Note 20] The method of Supplementary Note 19, wherein the controller controls the valve using information from the pressure sensor. [Appendix 21] A method for controlling an air-operated diaphragm pump, comprising: opening a valve fluidly connecting a source of air pressure to an actuation chamber of the diaphragm pump; monitoring one or more pressures of gas within the working chamber of the diaphragm pump; closing the valve when the pressure in the working chamber is equal to or greater than a target pressure; and opening the valve when the average magnitude of the monitored pressure is less than a target pressure by a predetermined value, the predetermined value varying during a stroke of the diaphragm pump. [Appendix 22] The method of Appendices 21, wherein the predetermined value varies according to the number of valve openings during the stroke. [Appendix 23] The method of Appendices 21, wherein the predetermined value varies depending on whether the diaphragm pump is filled or empty.

Claims

1. 1. A seating device for a cassette having a plug-in side and an opposite mounting side, comprising: a stationary frame member connected to a movable cassette mount by a plurality of linkages on a first side of the cassette mount and an opposite second side of the cassette mount, the linkages on the first side of the cassette mount being connected to a first fixed flange of the stationary frame member and the linkages on the second side of the cassette mount being connected to a second fixed flange of the stationary frame member; each of the plurality of linkages includes a swing arm having a first end pivotally coupled to a fixed flange and a second end coupled to an elongated slot in the cassette mount; the second end of the swing arm is configured to move in an arcuate path to move the cassette mount; The elongated slot limits movement of the cassette mount by the swing arm to linear movement toward or away from the stationary frame member.

2. 2. The seating apparatus of claim 1, wherein the cassette mount includes a first movable flange and a first rail on the first side of the cassette mount and a second movable flange and a second rail on the second side of the cassette mount, each movable flange having a surface generally parallel to the direction of movement of the cassette mount, the elongated slot formed in the movable flange and oriented perpendicular to the direction of movement of the cassette mount, and the first and second rails retain a mounting side of a cassette.

3. 3. The seating apparatus of claim 2, further comprising a handle assembly pivotally connected to the cassette mount, wherein movement of a handle of the handle assembly in a direction away from the stationary frame member causes the cassette mount to move away from the stationary frame member, and movement of the handle in a direction toward the stationary frame member causes the cassette mount to move toward the stationary frame member.

4. 4. The seating device according to claim 3, wherein the pivot connections of the handle assembly include a first pivot connection of a first handle arm to the first fixed flange, a second pivot connection of a second handle arm to the second fixed flange, a third pivot connection of the first handle arm to a handle swing arm connected to the first movable flange of the cassette mount, and a fourth pivot connection of the second handle arm to a handle swing arm connected to the second movable flange of the cassette mount, the first and third pivot connections and the second and fourth pivot connections being spaced apart from one another on the first and second handle arms.

5. 4. The seating apparatus of claim 3, further comprising a third fixed flange of the stationary frame member, the third fixed flange facing the handle assembly and generally perpendicular to the first and second fixed flanges, the handle assembly including a spring-loaded plunger configured to engage a hole or recess in the third fixed flange such that the cassette mount is locked in a retracted position when a handle of the handle assembly is moved toward the stationary frame member.

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