Closure assembly and method of operation thereof

Abstract

To provide an occlusion assembly for closing a folding type tube of a medical infusion device.SOLUTION: An occlusion assembly includes: first and second occlusion members which are positioned to be opposite from each other to be adjacent respectively to paired first and second foldable tubes such that a space is formed between them, while the space is located on the opposite side of the foldable tubes, and the occlusion members are adjacent to the foldable tubes; an expanding portion which forcibly moves portions of the occlusion members in a manner to be separate from each other to increase the size of the space, and forcibly moves a tube contact portion of each of the occlusion members relative to the foldable tubes adjacent to the occlusion members such that the foldable tubes are closed; and an actuator configured and positioned for moving the expanding portion.SELECTED DRAWING: Figure 54

Description

[Technical field]

[0001] The present invention relates generally to hemodialysis and similar dialysis systems, such as systems that allow for the treatment of blood or other bodily fluids outside the body. [Background technology]

[0002] Many factors make hemodialysis inefficient, difficult, and expensive, including the complexity of hemodialysis, safety concerns associated with hemodialysis, the large volumes of dialysate required for hemodialysis, etc. Furthermore, hemodialysis is typically performed in dialysis centers that require skilled technicians. Summary of the Invention [Problem to be solved by the invention]

[0003] Therefore, simplifying and improving the efficiency of dialysis procedures could have a significant impact on the cost of treatment or patient expenditure. [Means for solving the problem]

[0004] In one aspect of the invention, a drainage cassette for a dialysis unit includes a venous connection port connected to and in fluid communication with a venous blood line connector, an arterial connection port connected to and in fluid communication with an arterial blood line connector, a fluid channel fluidly connecting the venous connection port and the arterial connection port, a drainage outlet port in fluid communication with the fluid channel and configured to removably couple with a drainage connector of an exposed panel of the dialysis unit, and a valve configured to control flow in the fluid channel. The valve can be configured to controllably open and close fluid communication in the fluid channel between the drainage outlet port and the venous connection port, or to controllably open and close fluid communication in the fluid channel between the drainage outlet port and the arterial connection port. Such a configuration can allow for purging and / or cleaning of the venous and arterial lines to drain, for example, in preparation for treatment. Additionally, the drainage cassette can be detachable from the dialysis unit, allowing an operator to remove and replace blood contacting portions of the drainage cassette when preparing the dialysis unit to treat another patient.

[0005] In one embodiment, the drainage cassette can include an arterial connection port and a venous connection port, and a body that forms a fluid channel. A check valve can be configured to allow flow out of the fluid channel and out of the drain outlet port, and to prevent flow from the drain outlet port into the fluid channel. Thus, fluid or other material in the drain line downstream of the check valve can be prevented from entering the fluid channel. The valve that controls flow in the fluid channel can be a pneumatically controlled valve, and the pneumatically controlled port of the drainage cassette can be configured to removably mate with a port in an exposed panel of the dialysis unit, fluidly connecting the valve to the port in the exposed panel to allow control of the valve.

[0006] In one embodiment, the drainage cassette can include a latch configured to releasably lock the drainage cassette to the exposed panel. For example, the latch can include a handle and a male bayonet connector configured to engage a female bayonet receptacle on the panel of the dialysis unit. The latch can thus be operated to connect and disconnect the drainage cassette to the panel, for example, by inserting the bayonet connector into the receptacle and turning the handle. Such loading and unloading of the cassette can also couple / disconnect other components of the drainage cassette with one or more ports, electrical connectors or corresponding ports, connectors, etc. on the panel. For example, the drainage port, the pneumatic valve control port, and electrical connectors coupled to one or more sensors on the drainage cassette can be simultaneously coupled to corresponding ports / connectors on the panel in a single connection operation that can include pressing the drainage cassette against the panel and turning the latch handle.

[0007] The drainage outlet port can be in fluid communication with the fluid channel at a point above where the arterial and venous connection ports communicate with the fluid channel, for example, so that air in the fluid channel can be evacuated by introducing fluid at the connection port. In one embodiment, the fluid channel has a U-shape, with the arterial and venous connection ports fluidly connected to the fluid channel at the ends of the U-shape, and the drainage outlet port fluidly connected to the fluid channel at a central bend in the U-shape.

[0008] One or more sensors can be included to detect characteristics of the fluid in the fluid channel or elsewhere in the drainage cassette. For example, a conductivity sensor can be positioned to detect the conductivity of the fluid in the fluid channel, and a temperature sensor can be positioned to detect the temperature of the fluid in the fluid channel. The one or more sensors can be coupled to an electrical connector configured to electrically connect the one or more sensors to a corresponding electrical connector of the exposed panel. In one embodiment, the electrical connector and the drainage outlet port are configured to simultaneously couple to corresponding electrical connectors and drainage connectors of the exposed panel of the dialysis unit in a single connection operation. In some configurations, a pneumatic control port coupled to a valve can be configured to removably mate with a control port of the exposed panel and simultaneously couple to a corresponding control port in the same single connection operation used to connect the drainage port and the electrical connector.

[0009] The valve can be configured such that the drain outlet port is permanently open and in fluid communication with the arterial connection port and can controllably open and close fluid communication in the fluid channel between the drain outlet port and the venous connection port, or the drain outlet port can be permanently open and in fluid communication with the venous connection port and the valve can be configured to controllably open and close fluid communication in the fluid channel between the drain outlet port and the arterial connection port.

[0010] In another aspect of the invention, the blood circuit assembly and drainage cassette can be engageable with an exposed panel of the diagnostic section for operation in dialysis treatment and can be removable from the exposed panel for replacement without the use of tools. Such a configuration can allow easy replacement of all blood-contacting components of the dialysis unit, thereby allowing the dialysis unit to be used with multiple different patients (e.g., at a clinical site) while minimizing the risk of blood-derived substances from a previous patient coming into contact with treatment components of a subsequent patient. For example, the blood circuit assembly can include a pair of pneumatic pumps that circulate blood received from and returned to the patient through a circuit including the dialyzer unit, an air trap configured to remove air from the blood circulating in the circuit, a pair of dialyzer connections configured to connect to an inlet and an outlet of the dialyzer unit, and a pair of blood line connectors including an arterial blood line connector that receives blood from the patient and provides blood to the pneumatic pump, and an arterial blood line connector that returns blood to the patient. The pneumatic pump has a pneumatic control port configured to align and mate with a corresponding port located on the exposed panel of the dialysis unit by mounting the blood circuit assembly to the exposed panel and pressing the control port to engage the corresponding port. Thus, the blood circuit assembly can be relatively easily mounted to and removed from the panel of the dialysis unit. The drainage cassette can include a venous connection port connected to and in fluid communication with the venous blood line connector, an arterial connection port connected to and in fluid communication with the arterial blood line connector, a fluid channel fluidly connecting the venous connection port and the arterial connection port, a drainage outlet port in fluid communication with the fluid channel and configured to removably couple with the drainage connector of the exposed panel of the dialysis unit, and a valve configured to control flow in the fluid channel. Like the blood circuit assembly, as described above, the drainage cassette can be easily mounted to and removed from the panel of the dialysis unit for control by the dialysis unit during the treatment process and for replacement.

[0011] In one embodiment, the flexible tube can fluidly connect the pump, the air trap, the dialyzer connection, and the blood line connector of the blood circuit assembly. For example, the flexible tube can fluidly connect the arterial blood line connector to the inlet for the pump cassette, the outlet for the pump cassette to the dialyzer inlet connector, the dialyzer outlet connector to the inlet of the air trap, and the outlet of the air trap to the venous blood line connector. The blood line connector can be configured for a threaded luer type connection to the patient access and a press-fit type connection to the drainage cassette connection port. Such a configuration can allow for easy connection to the drainage cassette and can allow for disinfection of the connection, for example, a press-fit connection to the drainage cassette can allow disinfecting fluid to flow around the patient access connection of the connector. The drainage cassette can have other features as described above.

[0012] In another aspect of the invention, a blood circuit assembly for a dialysis unit includes a pair of pneumatic pumps for circulating blood received from a patient through a circuit including a dialyzer unit and returned to the patient, an air trap configured to remove air from the blood circulating in the circuit, a pair of dialyzer connections configured to connect to an inlet and an outlet of the dialyzer unit, a pair of blood line connectors including an arterial blood line connector that receives blood from the patient and provides blood to the pneumatic pump, and a venous blood line connector that returns blood to the patient, and flexible tubing fluidly connecting the pumps, the air trap, the dialyzer connections, and the blood line connectors. The pneumatic pump can have a pneumatic control port configured to be aligned and mated with a corresponding port located on an exposed panel of the dialysis unit by mounting the blood circuit assembly to the exposed panel and pressing the control port to engage the corresponding port.

[0013] The pump may also be formed, at least in part, by a single integral member that further forms a plurality of orientation channels for at least a portion of the flexible tubing. In one embodiment, the single integral member or other organized tray configuration forms an air trap cavity that receives the air trap. In some configurations, when the blood circuit assembly is mounted to the dialysis unit, the inlet of the air trap is supported by the air trap cavity or other support at a location above the outlet of the air trap. This configuration may allow for more effective removal of air from the blood line.

[0014] In another embodiment, a single integral part can form a pneumatic control port for the pump, a recessed chamber for the pump, chambers for a number of valves used to control flow through the pump, orientation channels for the flexible tubes that position the flexible tubes to engage with the closures when the assembly is mounted on the dialysis unit, and / or other features. For example, the organization tray can include circuit tube engagement members having holes through which the respective circuit tubes pass, which engage the tubes to allow the circuit tubes to be pulled and stretched to engage with the closures of the dialysis unit. For example, by ensuring that the various components are properly positioned on the panels of the dialysis unit, having a single part form multiple parts of the blood circuit assembly and / or precisely orienting the flexible tubes can make assembly of the blood circuit assembly easier and more effective.

[0015] In another embodiment, the flexible tubing can connect the components as follows: an arterial blood line connector can be connected to an inlet for the pump cassette, an outlet for the pump cassette can be connected to a dialyzer inlet connector, the dialyzer outlet connector can be connected to an inlet of an air trap, and the outlet of the air trap can be connected to a venous blood line connector.

[0016] In some embodiments, the blood circuit assembly can include an anticoagulant connection that engages an anticoagulant source and provides anticoagulant into the circuit. For example, an anticoagulant pump can be included, for example as part of a pump cassette, that pumps anticoagulant from the anticoagulant source into the circuit. The anticoagulant connection can include a vial holder and spike, and the anticoagulant source can be a vial of heparin.

[0017] In another aspect of the invention, a blood circuit assembly engagement device for a dialysis unit includes an actuator mounted on a panel of the dialysis unit adjacent to a plurality of control ports and movable between a holding position and an unloading position, a retainer element coupled to the actuator and configured to hold a blood circuit assembly mounted on the panel of the dialysis unit when the actuator is in the holding position and to release the blood circuit assembly from the panel of the dialysis unit when the actuator is in the unloading position, and an ejector element coupled to the actuator and configured to move the blood circuit assembly away from the panel when the actuator moves from the holding position to the unloading position. This configuration allows for more accurate and effective mounting, retaining, and removal of the blood circuit assembly from the dialysis unit. For example, if the retainer element is not positioned in the holding position when the blood circuit assembly is mounted on the panel, a user can easily confirm that the assembly is not properly engaged with the panel. Thus, the actuator can be used to eject the assembly, allowing replacement of the assembly on the panel.

[0018] In one embodiment, the actuator is pivotally mounted to the panel, and the retainer element is fixed to the actuator. The ejector element can be pivotable between an inactive position and an ejection position and can pivot based on movement of the actuator. For example, the actuator can be configured to be moved from the holding position and the ejection position by a user's thumb. In one configuration, a first blood circuit assembly engagement device and a second blood circuit assembly engagement device are provided on the panel, the first engagement device being disposed on a first side of the blood circuit assembly mounted on the panel, and the second engagement device being disposed on a second side of the blood circuit assembly mounted on the panel. The first side and the second side can be opposed to each other, whereby the actuators of the engagement devices are movable by the respective first and second thumbs of the user. For example, using both thumbs, the user can press the actuators to move the actuators away from each other and move the actuators from their respective holding positions to the ejection position. The ejector element can be configured to contact a portion of the pump chamber, such as a rear chamber wall of the pump, in the ejection position, and the retainer element can be configured to contact an outer surface of the blood circuit assembly to lock the blood circuit assembly in place when the actuator is in the holding position and the blood circuit assembly is mounted to the panel.

[0019] Also described herein are closure assemblies configured to facilitate opening and closing by closure of flexible tubing. In specific embodiments, the closure assemblies are associated with or form part of medical infusion devices, such as hemodialysis machines, peritoneal dialysis machines, plasma exchange machines, and the like, and can be controllably and automatically operated to facilitate the processing of fluids by such devices. The closure assemblies can be designed to position and secure tubing, and can include frames or other support mechanisms configured to provide tubing guides and / or be attached to or incorporated into the fluid processing assemblies of the devices of which they are a part. The closure assemblies can include tubing closures, which can be mechanisms configured and positioned to apply a force to the tubing associated with the closure assembly to close the tubing and release the force to open the tubing for fluid flow. The closure assemblies and tubing closures can be configured to include a single tube in one embodiment, or multiple tubes in other cases, whether the number of tubes is odd or even. Some closure assemblies can include tubing closures configured to close more than one pair of tubes, in particular tubing closures having separate closure members that close each of the pairs of collapsible tubes. The closure assembly can include an automatic actuator that operates the tubing closure, and in one embodiment can also include a manual actuator that provides an override function. The closure assembly can include a door designed and positioned to cover at least a portion of the included tubing and tubing closure mechanism. Such a closure assembly can include a safety mechanism, for example, to prevent release of the closure force on the tubing when the door is not in the closed position, and / or a convenience feature, for example, a retainer mechanism that holds the tube closure in the unclosed position when the door is opened when the tube closure is in the unclosed position.

[0020] In one aspect, various closure assemblies are described for closing at least one collapsible tube of a medical infusion device. In some embodiments, the closure assembly is configured to close at least one pair of collapsible tubes, and includes a first closure member and a second closure member for each pair of collapsible tubes, the first closure member being positioned adjacent to the first collapsible tube of the pair and the second closure member being positioned adjacent to the second collapsible tube of the pair when the tubes are placed in the closure assembly for operation. The first and second closure members are further positioned adjacent to each other such that spaces are formed between the first and second closure members. These spaces are present on the opposite side of each closure member from the collapsible tube to which it is adjacent. The closure assembly further comprises a spreader positioned within the space between the closure members and movable from a first position to a second position, whereby movement from the first position to the second position causes the spreader to force at least a portion of the first and second closure members away from one another to increase a size of the space therebetween and force a tube contact portion of each closure member into contact with an adjacent collapsible tube to close the collapsible tube. The closure assembly further comprises at least one actuator configured and positioned to move the spreader between the first position and the second position.

[0021] In some embodiments, the closure assembly comprises a frame configured to close at least one collapsible tube and comprising a piping guide configured to position the collapsible tube; a piping closure section mounted to the frame and comprising a closure member configured and positioned to controllably close or release the closure of the collapsible tube; a door hingedly mounted to the frame and positioned to cover the collapsible tube and at least a portion of the piping closure section when in a closed position and to provide user access to the collapsible tube when in an open position; and a switch configured and positioned to detect when the door is in the closed position and to enable operation of the piping closure section to release the closure of the collapsible tube only when the door is in the closed position.

[0022] In some embodiments, a closure assembly for closing at least one collapsible tube comprises a piping closure section comprising a closure member configured and positioned to controllably close or release the closure of the collapsible tube, an automated actuator operably coupled to the piping closure section such that substantially linear movement of at least a portion of the piping closure section moves the closure member from the closed position to the unclosed position, and an override mechanism operably coupled to the piping closure section such that upon manual operation of the override mechanism by a user, substantially linear movement of at least a portion of the piping closure section moves the closure member from the closed position to the unclosed position.

[0023] In some embodiments, a closure assembly for closing at least one collapsible tube comprises a frame comprising a piping guide configured to position the collapsible tube; a piping closure section mounted to the frame and comprising a closure member configured and positioned to controllably close or unclose the collapsible tube; a door hingedly mounted to the frame and positioned to cover at least a portion of the collapsible tube and the piping closure section when in a closed position and to provide user access to the collapsible tube when in an open position; and a retainer mechanism configured to be engaged by the door when the door is in the closed position and to allow operation of the piping closure section to close or unclose the collapsible tube when the door is in the closed position, and configured to engage with the piping closure section and hold the piping closure section in the unclosed configuration when the door is open while the piping closure section is positioned in the unclosed configuration.

[0024] In another aspect, a method of operating a closure assembly for closing at least a pair of collapsible tubes of a medical infusion device is disclosed. In one embodiment, the method includes moving a flaring portion of the closure assembly from a first position to a second position, where the flaring portion forces at least a portion of the first and second closure members away from each other in a space formed between the first and second closure members to increase the size of the space therebetween, forcing a tube contact portion of each closure member into contact with an adjacent collapsible tube to close the collapsed tube.

[0025] Other aspects of the invention relate generally to hemodialysis and similar dialysis systems. The exemplary embodiments described herein include, in one embodiment, interrelated products, alternative solutions to a particular problem, and / or a number of different uses of one or more systems and / or articles. Although the various systems and methods described herein are described in the context of hemodialysis, it should be understood that they are also applicable to other dialysis systems and / or extracorporeal systems capable of treating blood or other bodily fluids, such as hemofiltration, hemodialysis, etc.

[0026] According to one aspect of the invention, there is provided an enclosure with a portable hemodialysis unit, the hemodialysis unit comprising suitable components for performing hemodialysis, including a dialyzer, one or more pumps for circulating blood through the dialyzer, a dialysate source, and one or more pumps for circulating dialysate through the dialyzer. The enclosure can comprise a housing supporting the components of the hemodialysis unit and having a front panel on which blood circuit connections and dialysate fluid connections are located. For example, the front panel can support blood line connections for patient blood access, connections for reagent supplies, and dialyzer connections for both blood flow and dialysate flow. Thus, in one embodiment, an operator can complete all the necessary fluid circuit connections for the blood circuit and reagent supplies on the front panel of the housing. The enclosure can comprise a pair of vertical parallel doors hingedly attached to the housing at opposite ends of the front panel such that the doors can be moved between open and closed positions. When the doors are in the open position, the operator can access the blood circuit connections and the dialysate fluid connections. Additionally, when the doors are in the closed position, access to the patient and dialysate fluid connections can be blocked to retain heat within the housing suitable for disinfection during a disinfection cycle. For example, at least one of the doors can include a seal to resist air exchange between the interior and exterior of the housing to help retain heat and / or to help prevent the ingress of dust, debris, or other contaminants when the door is in the closed position.

[0027] In one embodiment, the vertical parallel doors are each attached to the housing through a hinge plate pivotally mounted to the door at a first end and pivotally mounted to the housing at a second end opposite the first end. Thus, the door can have two open positions, e.g., a first open position in which the blood circuit connection and the dialysate fluid connection are exposed and the hinge plate is close to the housing, and a second open position in which the hinge plate is away from the housing. One or more retaining members can be provided to hold the door in an open position relative to the corresponding hinge plate. For example, the retaining member can comprise at least one magnet attached to the door or the hinge plate that tends to hold the door in an open position relative to the hinge plate and the housing. Furthermore, the one or more retaining members can hold the hinge plate in a closed position relative to the housing, e.g., close to the housing, and / or hold the hinge plate in an open position away from the housing.

[0028] In one embodiment, at least one of the doors can include a container holder movable between a folded position and an open position, the container holder arranged to support a container, such as a reagent supply container. Additionally or alternatively, one or both of the doors can include a hook to support a control interface for the hemodialysis unit, such as a remote interface portion connected to the housing by a communications cable. These features facilitate easier access to the dialysis unit by supporting components in a convenient location.

[0029] In another embodiment, the front panel can include at least one flange portion that supports the blood lines of the blood circuit assembly. For example, the front panel can include several flange portions located around the periphery of the front panel, such as at the bottom corners and top edge of the front panel. The blood circuit lines leading to the patient can be relatively long (e.g., 3-4 feet or more) and can be wrapped around the front panel and held in place by the flange portions. The flange portions can be positioned to support the blood lines and allow the door to move to a closed position without contacting the blood lines, e.g., to prevent the blood lines from getting pinched at the door hinge points.

[0030] In one embodiment, the front panel blood circuit connections include arterial and venous blood line connectors for the blood circuit, and the front panel dialysate fluid connections include reagent supply connection points, a dialyzer dialysate connection, and blood line connection points that connect the arterial and venous blood lines to the directing circuit of the dialysis unit.

[0031] The hemodialysis unit can include a control interface connected to the housing by a flexible cable and configured to allow a user to interact with the hemodialysis unit. In one embodiment, the housing can include a control interface mounting area on the housing where the control interface can be mounted. For example, the control interface can include foldable legs or other supports such that the control interface can stand in a substantially vertical orientation on the housing.

[0032] In another embodiment, the housing can include an electronics section that is separate and isolated from a disinfection section that is heated to disinfect components of the hemodialysis unit. For example, the disinfection section can include all of the fluid circuit components, such as valves, pumps, tubing, etc., of the various parts of the dialysis unit. The electronics section can include motors, computers or other data processing equipment, computer memory, and / or other temperature sensitive electronics or other components. By isolating the electronics section (at least to some extent) from the disinfection section, components in the electronics section are not exposed to heat or other environmental conditions in the disinfection section during disinfection or other operations.

[0033] According to another aspect of the invention, the portable hemodialysis system can be configured such that the fluid circuit pumps of the dialysis unit are provided by a modular power unit, e.g., a unit that can be selectively connected or disconnected from the dialysis unit. As a result, if the power unit fails, it is not necessary to disable the entire dialysis system. Alternatively, the power unit can be replaced with another power unit to continue the treatment. For example, a modular assembly for a portable hemodialysis system can include a dialysis unit having a housing that contains suitable components for performing hemodialysis, such as a dialyzer, one or more pumps that circulate blood through the dialyzer, a dialysate source, and one or more pumps that circulate dialysate through the dialyzer. The housing can have a front panel on which the blood circuit connections and the dialysate fluid connections are located, e.g., on which an operator can connect the patient blood access, connect a reagent source, and / or connect the dialyzer. The modular assembly can also include a power unit having a housing for containing suitable components that provide operating power to the pumps of the dialysis unit. The power unit is selectively connected to the dialysis unit and is capable of providing power to the dialysis unit for the pump when connected to the dialysis unit, but is unable to provide power to the dialysis unit when disconnected from the dialysis unit. The power unit is selectively connected and disconnected from the dialysis unit by manipulation of a separate handle. For example, an operator may rotate or otherwise manipulate the separate handle to disconnect the power unit from the dialysis unit. In one embodiment, the dialysis unit and the power unit are each sized and weighted to be portable by a human.

[0034] In one embodiment, the pump of the dialysis unit is a pneumatic pump, and the power unit provides pneumatic power to the dialysis unit. For example, the power unit can provide pneumatic pressure and / or vacuum to the dialysis unit to power the pump. The power unit can include one or more pneumatic and / or vacuum pumps, and the dialysis unit can include a number of valves that control the application of pneumatic power to the pump. To facilitate use of the hemodialysis system at home, the power requirements of the power unit and dialysis unit are provided by standard household power, e.g., about 110V, 15 amp power. The dialysis unit provides power to the power unit, which can use the power to generate operating power for the pump.

[0035] According to another aspect of the invention, a blood circuit assembly for a dialysis unit can be configured to allow replacement of most or all of the blood circuit components in a single operation. For example, the blood circuit assembly can include a tissue tray, a pair of pneumatic pumps mounted on the tissue tray for circulating blood received from and returned to a patient through a circuit including a dialyzer unit, an air trap mounted on the tissue tray configured to remove air from blood circulating in the circuit, a pair of dialyzer connectors configured to connect to an inlet and an outlet of the dialyzer unit, and a pair of blood line connectors, one inlet blood line connector receiving blood from a patient and supplying the blood to the pneumatic pump and the other outlet blood line connector returning blood to the patient.

[0036] In one embodiment, an anticoagulant connection is provided for engaging an anticoagulant source and supplying anticoagulant to the blood circuit. For example, the anticoagulant connection can include an anticoagulant pump for pumping anticoagulant from an anticoagulant source, such as heparin, from a vial of heparin to the circuit. The anticoagulant connection can include a vial holder configured to hold two or more different sized vials and a spike for penetrating the vial. In one embodiment, the pair of pneumatic pumps, the anticoagulant connection, and the anticoagulant pump are part of a pump cassette.

[0037] In another embodiment, the blood circuit assemblies can be selectively mounted or removed from the dialysis unit. To aid in handling the blood circuit assemblies, the organizing tray can include a pair of handles configured for a user to grasp. Additionally, the organizing tray can include openings adjacent each handle to accommodate retaining tabs on the dialysis unit that engage the blood circuit assemblies to retain the blood circuit assemblies on the dialysis unit.

[0038] In one embodiment, the inlet blood line connector is connected to the inlet for the pump cassette, the outlet for the pump cassette is connected to the dialyzer inlet connector, the dialyzer outlet connector is connected to the inlet of the air trap, and the outlet of the air trap is connected to the outlet blood line connector. When the blood circuit assembly is mounted to the dialysis unit, the inlet of the air trap can be positioned, for example, above the outlet of the air trap to help capture air circulating in the circuit during treatment. The blood line connector is configured for a threaded luer type connection to the patient access and a press-fit type connection to the dialysis unit. Such a configuration allows an operator to engage the blood line connector with a standard luer type connector at the patient blood access, while more easily connecting the blood line connector to the dialysis unit after treatment (e.g., for subsequent disinfection and / or priming of the blood circuit).

[0039] In one embodiment, the organization tray can include a circuit tube engaging member having a hole or slot through which each circuit tube passes. The engaging member can engage each circuit tube to pull and stretch the circuit tube to engage with a closure of a dialysis unit. For example, the circuit tube of a blood circuit assembly can include silicone tubing that must stretch (thereby reducing diameter) to engage with a closure. The circuit tube engaging member can resist an operator's pull on the tube to stretch the tube into position to engage with the closure.

[0040] According to another aspect of the invention, a method for replacing a blood circuit assembly of a dialysis unit includes gripping a pair of handles on an organized tray of a blood circuit assembly to be mounted on the dialysis unit, disengaging locking tabs of the dialysis unit from the blood circuit assembly to release the blood circuit assembly from the dialysis unit, and pulling the handles on the organized tray of the blood circuit assembly to remove the blood circuit assembly from the dialysis unit. Disengaging the locking tabs can be performed by deflecting the locking tabs toward each other so that each locking tab moves toward the nearest handle. After removal of the blood circuit assembly, a replacement blood circuit assembly can be provided, and the openings of the organized tray of the replacement blood circuit assembly can be aligned such that each locking tab is received in each opening, and the organized tray can be pressed against the dialysis unit such that the locking tabs engage the replacement blood circuit assembly to mount the replacement blood circuit assembly to the dialysis unit. Mounting the replacement blood circuit assembly can further include connecting control ports on the dialysis unit to mating ports on the assembly such that fluid control signals are provided to pumps and valves of the blood circuit assembly. Other blood circuit connections can be made, such as inlet and outlet connections for a dialyzer, and blood line connectors can be connected to receive and deliver dialysate into the blood circuit.

[0041] According to another aspect of the invention, an air trap for a blood circuit in a dialysis unit includes a blood inlet supply line, a blood outlet supply line, and a container having a generally spherical inner wall, an inlet at an upper end of the container connected to the blood inlet supply line, and an outlet at a lower end of the container connected to the blood outlet supply line. The inlet can be offset from a longitudinal axis of the generally spherical wall such that blood entering the container through the inlet flows around the generally spherical wall in a spiral path. Such flow within the container helps remove air bubbles from the blood as it flows from the inlet to the outlet, with the removed air remaining near the upper end of the container. The inlet port is configured to introduce blood into the container in a direction generally tangential to the generally spherical inner wall of the container and / or in a direction generally perpendicular to the longitudinal axis of the container.

[0042] In one embodiment, a self-sealing port, for example in the form of a split membrane, can be positioned on the container and configured to allow fluid to be introduced into and withdrawn from the container by inserting a needleless device through the split membrane. The self-sealing port can be configured to self-clean as a disinfectant solution circulates through the container, for example, the port can be appropriately exposed to a flowing disinfectant solution to remove debris on the port and / or heat materials to achieve the desired disinfection.

[0043] According to another aspect of the present invention, a tube fixation structure for a blood circuit assembly includes an organizing tray supporting components of the blood circuit assembly and having a pair of tube engagement members, each engagement member having an aperture, a pair of patient inlet and outlet lines configured to connect with a patient access point for receiving fluid from a patient and / or supplying fluid to a patient, and a pair of stoppers on the patient inlet and outlet lines. The patient inlet and outlet lines can each pass through the aperture of each tube engagement member such that the stoppers engage with the tube engagement member. In this structure, the tube engagement members can resist pulling and stretching of the inlet and outlet lines when engaging the lines with the closure. The tube engagement members can be flexible to resist pulling downward on the lines while a user presses inward on the engagement members to place the inlet or outlet lines in the closure.

[0044] According to another aspect of the invention, a hemodialysis system includes a dialyzer mount configured to support a plurality of dialyzer units of various sizes and / or shapes and accommodate various distances between dialysate connections on the dialyzer units. The dialyzer mount is disposed on a front panel of the dialysis unit and can include a pair of flanges, each configured to engage a dialysate quick connect fitting connected to a dialysate port of the dialyzer. Each flange can also be configured to engage a groove of the quick connect fitting located between a base of the quick connect fitting and a sliding element of the quick connect fitting. For example, the dialyzer mount can include a pair of keyhole mechanisms, each keyhole mechanism including an upper insertion area sized to insert and receive a base of the quick connect fitting and a lower flange portion having a width less than the overall width of the base of the quick connect fitting and engaging with the groove of the quick connect fitting. The lower flange portion can include a pair of opposing flanges that engage the grooves to slide the quick connect fitting along the flange.

[0045] In one embodiment, the lower keyhole mechanism can include an adjustable support that is vertically movable. For example, the adjustable support can be moved along the opposing flanges. Thus, the adjustable support can be fixed at a number of different positions on the flanges to support the weight of the dialyzer. In one configuration, the adjustable support includes a "U" shaped member and at least one thumbscrew that can be tightened to lock the "U" shaped member in place.

[0046] According to another aspect of the invention, a blood line connector for a blood circuit of a hemodialysis unit can make two types of fluid-tight connections, for example, a threaded connection with a Luer connector at the patient access and a press-fit type connection at the dialysate circuit of the hemodialysis unit. For example, the blood line connector can include a tube connection end configured to sealingly engage a blood circuit tube, a patient access connection end with a frusto-conical member having an internal thread configured to engage a male-threaded patient access, and a pair of locking arms extending rearwardly from the frusto-conical member. Each of the locking arms can have a finger recess and a barbed portion configured to engage a mating connector on the dialysis unit at the barbed portion to lock the frusto-conical member in sealing engagement with the mating connector when making a press-fit type connection. When the finger recesses are biased toward each other, the barbs can be separated from the mating connector. In one embodiment, the patient access connection end can include a central tube extending from the center of the frusto-conical member. The female threads of the frustoconical member and central tube may be configured to mate with a female Luer type patient access connector or other suitable threaded connection.

[0047] According to another aspect of the invention, a method of operating a dialysis unit includes connecting blood line connectors of arterial and venous blood lines for the dialysis unit to a patient access connector in communication with a patient blood system. In one embodiment, the patient access connector requires a corresponding blood line connector and establishes a threaded engagement with the patient access connector to form a luer or screw type connection between the blood line connector and the patient access connector. The dialysis unit can be operated to draw blood from the patient access connector and pump it into the arterial blood line, subject the drawn blood to a dialysis process to produce treated blood, and return the treated blood to the patient through the venous blood line and other patient access connectors. The blood line connectors can then be disconnected from the corresponding patient access connector by unscrewing them, and the blood line connectors can be connected to a directing circuit of the dialysis unit. The blood line connectors can be connected to the directing circuit by a press-fit type connection with a corresponding connection point on the dialysis unit, for example, by pressing the blood line connector into the connection point and establishing a press-fit type connection.

[0048] According to another aspect of the invention, a reagent supply structure for a hemodialysis system can include a connector configured to supply two or more reagent materials for use in making a dialysate and configured to help prevent the reagent materials from being connected to an incorrect port. For example, a reagent supply source can include an E-shaped connector having three parallel prongs, two outer prongs disposed in a common plane and a central prong disposed above the common plane, a first supply line for a first reagent connected in fluid communication with one of the outer prongs, a second supply line for a second reagent connected in fluid communication with the other outer prongs, a liquid line connected in fluid communication with the central prong, and a container containing the first reagent having an inlet connected to the liquid line and an outlet connected to the first supply line for the first reagent. The E-shaped connector can help prevent improper connection of the first and second supply lines to the dialysis unit because the central prong located out of the plane of the two outer prongs ensures that the E-shaped connector connects in only one direction to the dialysis unit.

[0049] In one embodiment, the container contains a bicarbonate material suitable for use in producing dialysate for a hemodialysis system. The liquid line may be a water supply line that supplies water to the container and mixes it with bicarbonate (which may be a powder or other solid) and flows to the first supply line. The second supply line may be an acid supply line having a connector and supplying an acid material to the E-shaped connector. The reagent supply source may also include an acid bag spike that releasably engages with the connector of the acid supply line. The acid bag spike may include a spike member and a pair of spring clips at an end of the acid bag spike opposite the connector of the acid supply line to fluidly connect the acid bag spike to an acid bag or other acid source.

[0050] According to another aspect of the invention, a method of operating a hemodialysis system includes providing a dialyzer having an enclosure housing suitable components for performing hemodialysis, including a dialyzer, one or more pumps for circulating blood through the dialyzer, a dialysate source, and one or more pumps for circulating the dialysate through the dialyzer. The enclosure may include a housing supporting the components and having a front panel on which blood circuit and dialysate fluid connections are made. A reagent supply may be provided comprising an E-shaped connector, a first supply line for a first reagent connected in fluid communication with one of the outer prongs, a second supply line for a second reagent connected in fluid communication with the other of the outer prongs, a liquid line connected in fluid communication with the central prong, and a container for containing a first reagent having an inlet connected to the liquid line and an outlet connected to the first supply line for the first reagent. The E-shaped connector engages a connection point at the front panel of the dialysis unit to enable the dialysis unit to supply water to the liquid line of the reagent supply and to receive the first and second reagents from the first and second supply lines.

[0051] Other advantages and novel features of the present invention will become apparent from the following detailed description of various non-limiting embodiments of the present invention when considered in conjunction with the accompanying drawings. In the event that this specification and a document incorporated by reference include conflicting and / or conflicting disclosure, the present invention shall control. In the event that two or more documents incorporated by reference include conflicting and / or conflicting disclosure with respect to each other, the document having the later effective date shall control. [Brief description of the drawings]

[0052] [Figure 1] 1 is a schematic diagram of fluid handling components of a hemodialysis system according to an exemplary embodiment. [Diagram 2] FIG. 2 is a schematic diagram of fluid flow in the dialysis system of FIG. 1. [Diagram 3] FIG. 3 is a schematic diagram of fluid flow for the blood flow circuit of the embodiment of FIG. 2. [Figure 4] FIG. 3 is a schematic diagram of fluid flow for the balancing circuit of the embodiment of FIG. 2; [Diagram 5] 3 is a schematic diagram of fluid flow for the directing circuit of the embodiment of FIG. 2; [Figure 5A] 4 is a schematic fluid flow diagram illustrating the flow path for a drainage assembly in an exemplary embodiment. [Figure 6] FIG. 3 is a fluid flow schematic for the mixing circuit of the embodiment of FIG. 2. [Figure 7] FIG. 2 is a right front perspective view of an exemplary embodiment of a hemodialysis system. [Figure 7A] FIG. 2 is a perspective view of selected components of an exemplary embodiment power section; [Figure 7B] 1 is a schematic diagram of an exemplary embodiment of an air dehumidifier device. [Figure 7C] FIG. 7B is a perspective view of the dehumidifier configuration of the embodiment of FIG. 7A. [Figure 8] FIG. 8 is a left rear perspective view of the hemodialysis system of FIG. 7 . [Figure 9] FIG. 8 is a front view of the hemodialysis system of FIG. [Figure 10] 8 is a right front perspective view of the hemodialysis system of FIG. 7 with the door in a first open position. [Figure 11] Top view of the hemodialysis system of FIG. 10. [Figure 12] Front view of the hemodialysis system of FIG. 10. [Figure 13] Right side view of the hemodialysis system of FIG. 10. [Figure 14] Right front perspective view of the hemodialysis system of FIG. 7 when the door is in the second open position. [Figure 15] Top view of the hemodialysis system of FIG. 14. [Figure 16] Front view of the hemodialysis system of FIG. 14. [Figure 17] Front view of the hemodialysis system of FIG. 7 when the door is in the open position exposing the front panel of the system. [Figure 17A] Exploded perspective view of a control port assembly configured to interface with a blood pump assembly of an exemplary embodiment. [Figure 17B] Side cross-sectional view of the embodiment of FIG. 17A with the blood pump assembly engaged. [Figure 17C] Perspective view of a control port assembly having a pair of blood pump cassette latches and removal assemblies of an exemplary embodiment. [Figure 17D] Isolated view of a latch assembly with the ejector element in the retracted position of an exemplary embodiment. [Figure 17E] Isolated view of the latch assembly of FIG. 17D with the ejector element in the extended position of an exemplary embodiment. [Figure 17F] Front view of a blood pump cassette in a retained state on the panel of a dialysis unit of an exemplary embodiment. [Figure 17G] Cross-sectional view taken along line 17G-17G of FIG. 17F. [Figure 17H] Cross-sectional view taken along line 17H-17H of FIG. 17F. [Figure 17I] Front view of a blood pump cassette in a removed state in an exemplary embodiment. [Figure 17J] Cross-sectional view taken along line 17J-17J of FIG. 17I. [Figure 17K] Cross-sectional view taken along line 17K-17K of FIG. 17I. [Figure 18] FIG. 8 is a front view of a blood circuit assembly used in the system of FIG. 7. [Figure 18A] 1 is a perspective view of a blood pump having a drug holder in an exemplary embodiment. [Figure 19] 19 is a right perspective view of an organization tray for the blood circuit assembly of FIG. 18. [Figure 20] FIG. 19 is a left rear perspective view of the blood circuit assembly of FIG. 18 . [Figure 20A] FIG. 13 is a front exploded view of another embodiment of a blood pump cassette. [Figure 20B] FIG. 20B is an exploded rear view of the blood pump cassette of FIG. 20A. [Figure 20C] FIG. 20B is a front view of the bottom or rear plate of the blood pump cassette of FIG. 20A. [Figure 20D] FIG. 20B is a rear view of the bottom or rear plate of the blood pump cassette of FIG. 20A. [Figure 21] FIG. 8 is a left front perspective view of the front panel of the system of FIG. 7. [Figure 21A] FIG. 13 is a front view of another embodiment of a front panel assembly in an exemplary embodiment. [Figure 21B] FIG. 21B illustrates the front panel assembly of FIG. 21A with the top and center plate components of the blood pump cassette removed for clarity in an exemplary embodiment. [Figure 22] FIG. 8 is a front view of the front panel of the system of FIG. 7. [Figure 23] FIG. 8 is a front view of the front panel of the system of FIG. 7 having a pair of mounting features for dialyzers. [Figure 24] FIG. 1 is a side view of a dialyzer with quick connect fittings attached to the dialysate inlet / outlet ports of the dialyzer. [Diagram 25] FIG. 8 is a right perspective view of a reagent supply for use with the system of FIG. 7. [Figure 26] 26 is a perspective view showing the E-shaped connector for the reagent supply of FIG. 25 and the corresponding connection point on the front panel of the hemodialysis system. [Figure 27]FIG. 1 is a perspective view showing a pair of blood line connectors for a blood circuit assembly and corresponding connection points on the front panel of a hemodialysis system. [Figure 28] FIG. 28 is a side view of the blood line connector and connection points of FIG. 27. [Figure 29] FIG. 2 is a perspective view of another embodiment of a blood circuit assembly. [Diagram 30] 30 is a close-up view of a portion of the blood circuit assembly of FIG. 29. [Diagram 31] 1 illustrates an exemplary modular drainage cassette in an exemplary embodiment. [Diagram 32] 32 is an exploded view of the drainage cassette of FIG. 31 with the escutcheon plate in an exemplary embodiment positioned forward of the front wall of the drainage cassette. [Diagram 33] 32 is a perspective view of the front wall of the drainage cassette of FIG. 31 in an exemplary embodiment. FIG. [Diagram 34] FIG. 32 shows the main housing of the drainage cassette of FIG. 31 with the front wall removed for clarity in an exemplary embodiment. [Diagram 35] FIG. 32 is a rear perspective view of the drainage cassette of FIG. 31 in an exemplary embodiment. [Diagram 36] FIG. 13 illustrates the front panel with the drainage cassette removed in an exemplary embodiment. [Figure 37] FIG. 4 is a schematic diagram of a conductivity circuit in an example embodiment. [Figure 38] FIG. 38 is a diagram of an electrical waveform processed by the circuit of FIG. 37. [Figure 39] A representative graph of the noise / error sensitivity of the circuit of Figure 37 plotted versus the ratio of the unknown resistance / reference resistance of the circuit. [Diagram 40] 1 is a schematic diagram of an exemplary blood flow circuit of a hemodialysis system. [Figure 41A] FIG. 5 is a side view of a connector that can be used in the blood flow circuit of FIG. 4. [Figure 41B] 41B is a cross-sectional view of the connector of FIG. 41A. [Diagram 42] 41A and 41B with a wire and flexible tube attached. [Figure 43A]41 is a perspective view of another embodiment of a connector that can be used in the blood flow circuit of FIG. 40. [Figure 43B] Top view of the connector of Figure 43A. [Figure 43C] FIG. 43C is a cross-sectional view of the connector of FIG. 43B. [Figure 44A] 1 is a cross-sectional view of a flexible tube incorporating a conductive wire. [Figure 44B] 1 is a cross-sectional view of a flexible tube incorporating a conductive wire. [Figure 44C] 1 is a cross-sectional view of a flexible tube incorporating a conductive wire. [Fig.44D] 1 is a cross-sectional view of a flexible tube incorporating a conductive wire. [Diagram 45] FIG. 2 is a perspective view of a flexible dual lumen tube having a fluid carrying lumen and a wire carrying lumen. [Diagram 46] FIG. 43C is a cross-sectional view of a connector similar to that of FIGS. 43A-C with wires and tubing attached. [Figure 47] FIG. 1 is a plan view of an extracorporeal blood flow circuit used in a typical hemodialysis system. [Figure 48] FIG. 48 is a perspective view of a hemodialysis machine configured to receive and operate the extracorporeal blood flow circuit of FIG. 47. [Figure 49] Representative plots of resistance measured by the conductivity circuit of FIG. 37 under various conditions. [Figure 50] FIG. 2 is an exploded perspective view of a closure assembly from a front angle according to an embodiment of the present disclosure. [Figure 51] 2 is an exploded perspective view of the closure assembly of FIG. 1 from a rear angle. [Figure 52] FIG. 2 is a front perspective view of the closure assembly of FIG. 1 with the door open and the button pressed to indicate loading of a tube. [Figure 53] 2 is a close-up perspective view of the closure assembly of FIG. 1 showing the door engaging the switch when the door is closed. [Figure 54] 2 is a front view of the closure assembly of FIG. 1 without the door and frame to show the arm fully enclosing the flexible tube. [Figure 55]FIG. 2 shows the front of the closure assembly of FIG. 1 without the door and frame present to show the arms in the unclosed position. [Figure 56] 2 is a rear / top perspective view of the closure assembly of FIG. 1 with the actuator arm in a fully retracted position. [Figure 57] 2 is a rear perspective view of the closure assembly of FIG. 1 with the actuator arm in a fully extended position. [Figure 58] FIG. 2 is a side perspective view of some of the working components of the closure assembly of FIG. 1 in an unclosed state. [Figure 59] FIG. 2 is a side perspective view of some of the operative components of the closure assembly of FIG. 1 in a closed state. [Figure 60] 2 is a cross-sectional side view of an actuator of the closure assembly of FIG. 1 showing its position relative to a main spring for the assembly. [Figure 61] A diagram showing the closure assembly of Figure 50 mounted to a front panel assembly of a hemodialysis machine according to an embodiment of the present disclosure. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0053] Aspects of the present invention will now be described with reference to exemplary embodiments with reference to the drawings, in which like numerals refer to like elements, and in which: Various aspects of the present invention relate generally to novel systems such as hemodialysis, including hemofiltration systems, hemodiafiltration systems, plasma exchange systems, etc. Thus, although the various systems and methods described herein are described in the context of hemodialysis, it should be understood that they are also applicable to other dialysis systems and / or extracorporeal systems capable of treating other bodily fluids, such as blood or plasma.

[0054] As described below, a hemodialysis system typically includes a blood flow path and a dialysate flow path. It should be noted that in these flow paths, the fluid flow is not necessarily linear, and there can be any number of "branches" in the flow path through which the fluid can flow from the inlet of the flow path to the outlet of the flow path. Examples of such branches are described in detail below. In the blood flow path, blood is drawn from the patient and returned to the patient after passing through a dialyzer. The blood is processed by the dialyzer, and waste molecules (e.g., urea, creatinine, etc.) and water pass from the blood through the semipermeable membrane of the dialyzer to a dialysate solvent that passes through the dialyzer by the dialysate flow path. In various embodiments, blood can be obtained from the patient through two lines (e.g., an arterial line and a venous line, i.e., a "dual needle" flow), or in one embodiment, blood can be withdrawn from the patient and returned through the same, i.e., catheter needle (e.g., the two lines or lumens can both be in the same needle, i.e., a "dual lumen" flow configuration). In yet other embodiments, a "Y" or "T" site is used to withdraw blood from and return blood to the patient through a single patient connection with two branches (one for the withdrawn blood flow path and one for the return blood flow path, i.e., a "single needle" flow configuration). The patient can be any subject requiring hemodialysis or similar treatment, including non-human subjects such as dogs, cats, monkeys, and humans.

[0055] In the dialysate flow path, fresh dialysate is created and passed through the dialyzer to treat blood from the blood flow path. Additionally, the dialysate can be equalized (i.e., equalize pressure between the dialysate and blood) precisely, or in some embodiments, to within at least about 1-2% of the blood pressure, for blood treatment in the dialyzer. In one embodiment, it may be desirable to maintain a large pressure differential (positive or negative) between the blood flow path and the dialysate flow path. After passing through the dialyzer, the spent dialysate, including waste molecules (as described below), is discarded by a predetermined method. In one embodiment, the dialysate can be recirculated in a "multi-pass" configuration, which may be advantageous for trapping relatively large molecules with low mobility that traverse the dialyzer. In one embodiment, a suitable heater, such as an electrical resistance heater, can be used to heat the dialysate before treating the blood in the dialyzer. For example, an ultrafiltration filter can be used to filter the dialysate to remove contaminants, infectious organisms, debris, and the like. The ultrafiltration filter can have a pore size selected to prevent such species from passing through. For example, the pore size can be less than about 0.3 micrometers, less than about 0.2 micrometers, less than about 0.1 micrometers, or less than about 0.05 micrometers, etc. Dialysates are used to remove waste molecules (e.g., urea, creatinine, ions such as potassium, phosphate, etc.) and water from the blood by solute movement associated with osmosis or filtration and into the dialysate, which are well known to those skilled in the art.

[0056] Dialysate typically contains various ions such as sodium, chloride, bicarbonate, potassium, and calcium in concentrations similar to normal blood. In one embodiment, bicarbonate may have a slightly higher concentration than that found in normal blood. Dialysate is typically made by mixing water from a water supply with one or more components, including "acid" (which may include various species such as acetic acid, dextrose, NaCl, CaCl, KCl, MgCl, etc.), sodium bicarbonate (NaHCO 3), and / or sodium chloride (NaCl). Preparation of dialysate, including use of appropriate salt concentrations, osmolality, pH, etc., is well known to those of skill in the art. As described in more detail below, the dialysate does not have to be prepared at the same time that it is used to treat blood. For example, the dialysate can be prepared simultaneously with or prior to dialysis and stored, such as in a dialysate storage container.

[0057] In a dialyzer, the dialysate and blood are typically separated by a semipermeable membrane. The semipermeable membrane is typically made of a polymer, such as cellulose, polyarylethersulfone, polyamide, polyvinylpyrrolidone, polycarbonate, or polyacrylonitrile, that allows transport of ions and small molecules (e.g., urea, water, etc.) during blood processing, but does not allow mass transport or solute movement associated with filtration. In some embodiments (e.g., high flux dialyzers), larger molecules, such as β2-microglobulin, may pass through the membrane. Also, in some embodiments, ions and molecules may pass through the dialyzer by convection, for example, when a hydrostatic pressure difference exists across the semipermeable membrane.

[0058] It should be noted that "fluid" as used herein means anything that has fluid properties, including, but not limited to, gases such as air, and liquids such as water, aqueous solutions, blood, and dialysis fluids.

[0059] FIG. 1 is a schematic block diagram of a fluid circuit of a hemodialysis system incorporating various aspects of the invention. In this illustrated embodiment, the dialysis system 5 includes a blood flow circuit 141 that draws blood from a patient, passes the blood through a dialyzer 14, and returns the treated blood to the patient. A balancing circuit or internal dialysate circuit 143 receives dialysate from the ultrafilter 73, passes the dialysate through the dialyzer 14, and receives spent dialysate from the dialyzer 14. A directing circuit or external dialysate circuit 142 provides fresh dialysate to the ultrafilter 73 and receives spent dialysate (directed to drain 31) from the internal dialysate circuit 143. The directing circuit 142 can also receive water from the water supply 30 and pass the water to a mixing circuit 25. The mixing circuit 25 creates dialysate using water from the directing circuit 142 and reagent components 49, such as citrate, salts, and bicarbonates, which can be received from renewable sources. The mixing circuit 25 can, for example, create dialysate during and / or prior to dialysis, as needed. The fresh dialysate created by the mixing circuit 25 is provided to the directing circuit 142, which can provide the dialysate to the ultrafilter 73, as described above. The directing circuit 142 can include a heater to heat the dialysate to an appropriate temperature and / or to heat fluids in the disinfection system. For example, a line 67 (shown in dotted lines) can be connected between the blood flow circuit 141 and the directing circuit 142 for disinfection of the hemodialysis system.

[0060] Figure 2 is a schematic diagram showing more detailed circuitry for the dialysis system 5 shown in Figure 1. Of course, it should be understood that Figure 2 is only one possible embodiment of the general hemodialysis system of Figure 1, and that other fluid circuits, modules, flow paths, layouts, etc. are possible in other embodiments. Examples of such systems are described in more detail below and referenced in the following documents, each of which is incorporated herein by reference: No. 12 / 072,908 filed on February 27, 2008, U.S. Provisional Patent Application No. 60 / 903,582 filed on February 27, 2007, U.S. Provisional Patent Application No. 60 / 904,024 filed on February 27, 2007, U.S. Patent Application No. 11 / 871,680 filed on October 12, 2007, U.S. Patent Application No. 11 / 871,712 filed on October 12, 2007, U.S. Patent Application No. 11 / 871,787 filed on October 12, 2007, U.S. Patent Application No. 11 / 871,793 filed on October 12, 2007, or U.S. Patent Application No. 11 / 871,803 filed on October 12, 2007.

[0061] The blood flow circuit 141 includes an anticoagulant source 11 and a blood flow pump 13 that pumps blood from the patient through the dialyzer 14 and returns the blood to the patient. The anticoagulant source 11 is not shown in the blood path toward the dialyzer, but can be located in another suitable location, such as any location upstream or downstream of the blood flow pump 13. The balancing circuit 143 includes two dialysate pumps 15 that pump dialysate to the dialyzer 14, and a bypass pump 35. Blood flow through the blood flow circuit 141, in one embodiment, is synchronized with the dialysate flow in the dialysate flow path. In one embodiment, the dialysate flow into and out of the dialyzer 14 and the balancing circuit 143 is balanced using a balancing chamber in the balancing circuit 143. The directing circuit 142 includes a dialysate pump 159 that pumps dialysate from a dialysate tank 169 through the heater 72 and / or ultrafilter 73 to the balancing circuit 143. The directing circuit 142 also receives effluent from the balancing circuit 143 and directs it to the drain 31. In one embodiment, the blood flow circuit 141 may be connected to the directing circuit 142 through line 67, for example, for disinfection as described above. The dialysate in the dialysate tank 169 is provided by the mixing circuit 25. The mixing circuit 25 produces dialysate using water from the water supply 30 and dialysate components 49 (e.g., bicarbonate and acid) provided through the directing circuit 142. A series of mixing pumps 180, 183, 184 are used to mix the various components to produce the dialysate.

[0062] 3 is a close-up view of the blood flow circuit 141 of this exemplary embodiment. During normal operation, blood flows from the patient through the blood flow pump 13, through the arterial line 203, to the dialyzer 14 (the direction of flow during normal dialysis is indicated by arrow 205, although in some modes of operation the flow may be in a different direction, as described below). Optionally, an anticoagulant can be introduced into the blood from an anticoagulant source through an anticoagulant pump 80. After passing through the dialyzer 14 and undergoing dialysis, the blood optionally passes through an air trap and / or blood sample port 19 and returns to the patient through the venous line 204. The pump 13 can include, for example, a pump 23 actuated by a control fluid.

[0063] For example, in one embodiment, the blood flow pump 13 can include two (or more) pod pumps 23. In this example, each pod pump can include a rigid chamber with a flexible diaphragm or membrane dividing each chamber into a pump compartment and a control compartment. The compartments can be provided with four inlet / outlet valves, two for the pump compartment and two for the control compartment. The valves for the control compartments of the chambers can be bidirectional proportional valves, one connected to a first controlled fluid source (e.g., a high pressure air source) and the other connected to a second controlled fluid source (e.g., a low pressure air source) or a vacuum source. During operation of the pod pump 23, the fluid valves can be opened and closed to direct the flow of fluid. Non-limiting examples of pod pumps are described in U.S. Provisional Patent Application No. 60 / 792,073, filed April 14, 2006, or U.S. Patent Application No. 11 / 787,212, filed April 13, 2007, each of which is incorporated herein by reference. When there is more than one pod pump, the pod pumps can be operated in any suitable manner, such as synchronously, asynchronously, in phase, or out of phase. For example, in some embodiments, two pumps can be operated out of phase to affect the pumping cycle, such as one pump chamber filling while the second pump chamber empties. Any phase relationship between 0 degrees (pod pumps filling and emptying simultaneously) and 180 degrees (one pod pump filling while the other pump empties) can be selected to provide a desired pumping cycle. A 180 degree phase relationship can produce continuous flow into and out of the set of pod pumps. For example, this is beneficial when continuous flow is desired for use with dual needle or dual lumen catheter flow. However, for single needle / single lumen flow, it is beneficial to set a 0 degree phase relationship. With a 0 degree relationship, the pod pump fills from the needle first, then carries blood through the blood flow path and returns blood to the patient using the same needle.Additionally, to achieve a push / pull relationship across the dialyzer (hemodialysis or continuous backflush), in one embodiment, a phase run between 0 degrees and 180 degrees can be utilized.

[0064] An anticoagulant (e.g., heparin or other suitable anticoagulant) may be contained in a vial 11 (or other source of anticoagulant, such as a tube or bag), and blood flow circuit 141 may include a spike 201 (which in one embodiment is a needle) capable of piercing a seal on the vial. Spike 201 may be made of plastic, stainless steel, or other suitable material, and in one embodiment may be made of a material that can be sterilized, e.g., the material can withstand sufficient high temperatures and / or radiation during sterilization.

[0065] In one embodiment, the anticoagulant pump 80, acting as a metering chamber, can be used to control the flow of anticoagulant into the blood circuit. The anticoagulant pump 80 can be a pod pump or a diaphragm metering pump and / or can be actuated by a control fluid such as air. For example, the anticoagulant pump 80 can comprise a rigid chamber with a flexible diaphragm dividing the chamber into a pump compartment and a control compartment. One valve for the control compartment of the chamber can be connected to a first control fluid source (e.g., a high pressure air source) and the other valve can be connected to a second control fluid source (e.g., a low pressure air source) or a vacuum source. The valve for the pump compartment of the chamber can be opened and closed in coordination with the control compartment to control the flow of anticoagulant into the blood. In one embodiment, air supplied through a filter 81 can be introduced into the blood flow path by the anticoagulant pump 80, for example, to supply air into the vial 11 before or after anticoagulant is drawn from the vial.

[0066] Fluid management system ("FMS") measurements can be used to measure the volume of fluid pumped through the pump chamber during one stroke of the membrane or to detect air in the pump chamber. FMS methods are described in U.S. Pat. Nos. 4,808,161, 4,826,482, 4,976,162, 5,088,515, and 5,350,357, which are incorporated herein by reference in their entirety. In an exemplary embodiment, the volume of liquid pumped by an anticoagulant pump, dialysate pump, or other diaphragm fluid pump is determined using an FMS algorithm that utilizes the change in chamber pressure to calculate volume measurements at the end of the fill stroke and the end of the pump stroke. The difference between the calculated volumes at the end of the fill stroke and the end of the pump stroke can be used to determine the actual stroke volume. This actual stroke volume can be compared to the expected stroke volume for a particular size chamber. If the actual and predicted stroke volumes differ significantly, the stroke will not be completed properly and an error message can be generated.

[0067] The blood flow circuit 141 may also include an air trap 19 to remove any air bubbles that may be present in the blood flow path. In one embodiment, the air trap 19 may separate any air that may be present from the blood by gravity and / or may include a port for sampling the blood.

[0068] Figure 4 is a close-up view of the balancing circuit 143 in the embodiment of Figure 2. In the balancing circuit 143, dialysate flows from the optional ultrafilter 73 into the dialysate pump 15. In this embodiment, the dialysate pump 15 includes two pod pumps 161, 162, two balancing chambers 341, 342, and a pump 35 that bypasses the balancing chambers 341, 342. The balancing chambers 341, 342 consist of rigid chambers with a flexible diaphragm that divides the chamber into two separate fluid compartments, configured such that the entry of fluid into one compartment is used to expel fluid from the other compartment, and vice versa. Non-limiting examples of pumps that can be used as pod pumps and / or balance chambers are described in U.S. Provisional Patent Application No. 60 / 792,073, filed April 14, 2006, or U.S. Patent Application No. 11 / 787,212, filed April 13, 2007.

[0069] In one embodiment, flow balancing in the internal dialysate circuit operates as follows: one set of pneumatic valves 211, 212, 213, 241, 242 operate in a synchronized and controlled manner together, with valves 211, 212, 213 grouped together and valves 241, 242 grouped together, and a second set of pneumatic valves 221, 222, 223, 231, 232 also operate in a synchronized and controlled manner together, with valves 221, 222, 223 grouped together and valves 231, 232 grouped together. At a first time point, the first set of valves 211, 212, 213, 241, 242 are open and the second set of valves 221, 222, 223, 231, 232 are closed. Fresh dialysate flows into the balancing chamber 341 and spent dialysate flows from the dialyzer 14 into the pod pump 161. Because valve 221 is closed, fresh dialysate does not flow into the balancing chamber 342. As fresh dialysate flows into the balancing chamber 341, the spent dialysate in the balancing chamber 341 is expelled and exits the balancing circuit 143 (because valve 223 is closed, the spent dialysate does not enter the pod pump 161). At the same time, the pod pump 162 pushes the spent dialysate present in the pod pump (through valve 213, which is open) into the balancing chamber 342 (valves 242, 222 are closed, ensuring that the spent dialysate flows into the balancing chamber 342). This causes the fresh dialysate contained in the balancing chamber 342 to exit the balancing circuit 143 and enter the dialyzer 14. Additionally, the pod pump 161 draws the spent dialysate from the dialyzer 14 into the pod pump 161.

[0070] Once the pod pump 161 and balancing chamber 341 are filled with dialysate, the first set of valves 211, 212, 213, 241, 242 are closed and the second set of valves 221, 222, 223, 231, 232 are opened. While valve 221 is open, valve 212 is open so that fresh dialysate flows into balancing chamber 342 instead of balancing chamber 341. As fresh dialysate flows into balancing chamber 342, the spent dialysate therein is displaced and exits the balancing circuit because valve 213 is now closed. Additionally, the pod pump 162 draws spent dialysate from the dialyzer into the pod pump while spent dialysate is prevented from flowing into the pod pump 161 because valve 232 is now closed and valve 222 is now open. Valves 232, 211 are closed and valve 223 is open, causing pod pump 161 to push the used dialysate contained within the pod pump (from the previous step) into balancing chamber 341. This induces fresh dialysate contained within balancing chamber 341 into dialyzer 14 (because valve 241 is now open and valve 212 is closed). At the end of this step, pod pump 162 and balancing chamber 342 are filled with dialysate. This returns the state of the system to the configuration at the beginning of this description, so that the cycle can be repeated to ensure a constant flow of dialysate to and from dialyzer 14. In one embodiment, the fluid (e.g., air) pressure on the control side of the balance chamber valve is monitored to ensure that the balance chamber valve is functioning properly (e.g., open and closed).

[0071] As a specific example, a vacuum (e.g., 4 psi vacuum) can be applied to the ports of the first set of valves to open them, and a positive pressure (e.g., 20 psi air pressure) can be applied to the second set of valves to close them (or vice versa). Each pod pump urges dialysate into one of the balancing chambers 341, 342. By forcing dialysate into a given volume of the balancing chamber, an equal amount of dialysate is squeezed out of the remaining volume of the balancing chamber by the diaphragm. In each balancing chamber, a given volume is occupied by fresh dialysate going to the dialyzer, and the remaining volume is occupied by spent dialysate coming from the dialyzer. Thus, the volume of dialysate entering the dialyzer and the volume of dialysate leaving the dialyzer are kept approximately equal.

[0072] The bypass pump 35 can direct the dialysate flow from the dialyzer 14 through the balancing circuit 143 without passing through any of the pod pumps 161, 162. In this embodiment, the bypass pump 35 is a pod pump similar to that described above, with rigid chambers and flexible diaphragms dividing each chamber into a fluid compartment and a control compartment. This pump can be the same or different than the other pod pumps and / or metering pumps described above. When a control fluid is used to operate the bypass pump 35, the pressure on the outgoing (used) dialysate side of the dialyzer is further reduced, further ultrafiltering fluid from the blood in the dialyzer. This causes a net fluid to flow from the patient's blood through the dialyzer and ultimately to the drain. Such a bypass is useful, for example, in reducing the amount of fluid a patient has, which may increase due to the patient's inability to eliminate excess fluid (mainly water) through the kidneys. As shown in FIG. 4, the bypass pump 35 can be controlled by a control fluid (e.g., air) independent of the operation of the pod pumps 161, 162. With this configuration, the dialysate pump does not have to operate disproportionately or out of phase with the blood pump to achieve said fluid removal from the patient, making the net fluid removal from the patient easier to control.

[0073] To balance flow throughout the dialyzer, the blood flow pump, the pumps in the balancing circuit, and the pumps in the directing circuit (described below) can be operated in tandem to ensure that the flow into the dialyzer is approximately equal to the flow leaving the dialyzer. If ultrafiltration is required, the ultrafiltration pump (if present) can be operated independently of some or all of the other blood and / or dialysate pumps to achieve the desired ultrafiltration rate.

[0074] To prevent gassing of the dialysate, the balancing circuit pump can be kept under pressure above atmospheric pressure. In contrast, however, the blood flow pump and the directing circuit pump use pressure below atmospheric pressure to pull the diaphragm towards the chamber wall to complete the filling stroke. Because fluid moves across the semipermeable membrane of the dialyzer and the balancing circuit pump operates at positive pressure, the balancing circuit pump can use information from the blood flow pump to synchronize the balancing circuit chamber's pumping stroke to the dialyzer with the pumping stroke of the blood pump.

[0075] In one embodiment, when operating in such a balancing mode, without pumping pressure from the blood flow pump, the balancing circuit pump diaphragm will push fluid across the dialyzer into the blood and the other pods in the balancing circuit will not fill completely. Therefore, the blood flow pump reports when it is actively pumping a stroke. When the blood flow pump is pumping a stroke, the internal dialysate pump operates. When the blood flow pump is not pumping blood, the valves controlling the flow from the dialyzer to the internal dialysate pump (and other balancing valves grouped with these valves as described above) are closed to prevent fluid transfer from the dialysate side to the blood side from occurring. While the blood flow pump is not pumping, the internal dialysate pump is effectively frozen, and the pumping stroke of the internal dialysate pump will resume once the blood flow pump resumes pumping. The internal dialysate pump fill pressure can be set to a minimum positive value to ensure that the pump operates above atmospheric pressure with minimum impedance. Additionally, the internal dialysate pump delivery pressure is set to the blood flow pump pressure to closely match the pressure on either side of the dialyzer, minimizing flow across the dialyzer during the delivery stroke of the internal dialysate pump.

[0076] In another embodiment, the internal dialysate pump delivers dialysate to the dialyzer at a pressure slightly higher than the pressure at which blood is delivered to the dialyzer. This delivers clean dialysate to the dialyzer in a perfectly balanced chamber. On the return side, the internal dialysate pump fills with spent dialysate from the dialyzer at a pressure slightly lower than the outlet pressure of the blood side of the dialyzer, ensuring that there is enough dialysate in the balance chamber to complete all strokes. The flows across the semipermeable membrane caused by these pressure differences tend to cancel each other out, and the pumping algorithm otherwise tries to match the average pressures on the dialysate and blood sides of the dialyzer.

[0077] Since stagnant blood flow can lead to thrombosis, it is generally beneficial to keep blood flow as continuous as possible during treatment. Also, if the blood flow pump's delivery rate is discontinuous, the balancing pump may pause the stroke more frequently, resulting in discontinuous and / or low dialysate flow rates. However, the flow through the blood flow pump may become discontinuous for various reasons. For example, to provide a safe pumping pressure for the patient, pressure may be limited in the blood flow pump, e.g., to +600mmHg and / or -350mmHg. For example, in the case of dual needle flow, the two pod pumps of the blood flow pump can be programmed to operate 180 degrees out of phase with each other. This phasing is always feasible if there are no pressure limitations. However, these pressures are limited to provide a safe blood flow for the patient. If there is high impedance during the fill stroke (due to small needles, very viscous blood, small patient access, etc.), a negative pressure limit may be reached, resulting in a slower fill flow rate than desired. Thus, the pumping stroke must wait for the previous filling stroke to finish, resulting in a pause in the pumping flow rate of the blood flow pump. Similarly, for single needle flow, the blood flow pumps operate at 0 degrees phase and the pod pumps of the two blood flow pumps empty and fill simultaneously. Once both pod pumps are filled, the volume of the two pod pumps is pumped. In one embodiment, in a sequence of actuations, the first pod pump fills first, then the second pod pump, and then the first pod pump empties first, then the second pod pump. Thus, flow in a single needle or single lumen configuration may be discontinuous.

[0078] One way to control the pressure saturation limit is to limit the desired flow rate to the slowest fill and pump strokes. This results in a slower blood pump flow rate, but the flow rate is still known and more continuous, allowing for a more accurate and continuous dialysate flow rate. Another way to make the blood flow rate more continuous with a single needle operation is to use the maximum pressure to fill the pod so that the fill time is minimized. The desired pump time can then be set to the total desired stroke time minus the time taken for the fill stroke. However, the less continuous the blood flow becomes, the more the dialysate flow rate must be adjusted upward during blood pumping to the dialyzer to compensate for the time the dialysate pump is stopped while the blood pump is filling. If this is done with the correct timing, the average dialysate flow rate over multiple strokes can be matched to the desired dialysate flow rate.

[0079] FIG. 5 is a close-up view of the directing circuit 142 of the embodiment of FIG. 2. In this embodiment, the directing circuit 142 can supply dialysate from the dialysate tank 169 through the dialysate pump 159 to the heater 72 and ultrafilter 73. The heater 72 can be used to warm the dialysate to body temperature and / or a temperature such that the blood in the blood flow circuit is heated by the dialysate and the blood returning to the patient is at or above body temperature. In one embodiment, the heater 72 is connected to a control system so that incorrectly heated dialysate (i.e., dialysate that is too hot or too cold) is recycled (e.g., returned to the dialysate tank 169) or sent to drain instead of being sent to the dialyzer. The heater 72 can also be used for disinfection or sterilization in some embodiments. For example, water can be passed through the hemodialysis system and heated using a heater to a temperature that can be disinfected or sterilized, such as about 70° C., about 80° C., about 90° C., about 100° C., about 110° C., etc.

[0080] Dialysate flow through the directing circuit 142 can be controlled (at least in part) by operation of the dialysate pump 159. The dialysate pump 159 can also control the flow through the balancing circuit 143. For example, as described above, fresh dialysate from the directing circuit 142 flows into the balancing chambers 341, 342 of the balancing circuit 143. The dialysate pump 159 can be used as a driving force to force the fresh dialysate into these balancing chambers. In one embodiment, the dialysate pump 159 includes, for example, a pod pump similar to those described above. The dialysate can also be filtered, for example, using an ultrafiltration filter 73 to remove contaminants, infectious organisms, pathogens, pyrogens, debris, and the like.

[0081] The ultrafilter 73 can be placed at any suitable location in the dialysate flow path, such as, for example, between the directing and balancing circuits as shown, and / or the ultrafilter 73 can be incorporated into the directing or balancing circuits. If an ultrafilter is used, the pore size can be selected to prevent species from passing through the filter.

[0082] In one embodiment, the ultrafiltration filter 73 may be operated such that waste from the filter (e.g., retentate stream) is sent to a waste stream, such as waste line 39 in FIG. 5. In one embodiment, the amount of dialysate flowing into the retentate stream may be controlled. For example, if the retentate is too cold (i.e., the heater 72 is not functioning or does not heat the dialysate to a sufficient temperature), the entire dialysate stream (or at least a portion of the dialysate) may be diverted to waste line 39 and, optionally, recycled to the dialysate tank 169 using line 48. The flow from the filter 73 may also be monitored for a number of reasons, such as, for example, with a temperature sensor (e.g., sensors 251, 252) or a conductivity sensor (to verify dialysate concentration, e.g., sensor 253). Examples of such sensors are described below, and further non-limiting examples are referenced by U.S. Patent Application Serial No. 12 / 038,474, filed February 27, 2008.

[0083] The ultrafilter and dialyzer can provide an extra screening method for the removal of contaminants, infectious microorganisms, pathogens, pyrogens, debris, etc. Thus, any contaminant must pass through both the ultrafilter and the dialyzer before reaching the patient's blood. If the integrity of either the ultrafilter or the dialyzer is compromised, the sterility of the dialysate can be maintained and contaminants can be prevented from entering the patient's blood.

[0084] The directing circuit 142 may also route spent dialysate from the balancing circuit to a drain, e.g., through waste line 39 to drain 31. The drain may be, for example, a municipal drain or a separate container that holds water (e.g., spent dialysate) to be appropriately treated. In one embodiment, one or more check or "one-way" valves (e.g., check valves 215, 216) are used to control the waste flow from the directing circuit 142 and system 5. Additionally, in one example, a blood leak sensor (e.g., sensor 258) may be used to determine whether blood is leaking through the dialyzer 14 into the dialysate flow path. A liquid sensor may also be placed in the bottom collection tray of the hemodialysis unit to indicate leakage of blood and / or dialysate from the fluid circuit.

[0085] The directing circuit 142 can receive water from a water supply 30, e.g., a water container such as a bag, and / or a device capable of generating water, such as a reverse osmosis device. In one embodiment, the water entering the system can be set to a certain purity, e.g., having an ion concentration below a certain value. The water entering the directing circuit 142 can be sent to various locations, e.g., the mixing circuit 25 for generating fresh dialysate and / or the waste line 39. In one embodiment, the valves to the drain 31 and the various recycle lines are opened, and the conduit 67 is connected between the directing circuit 142 and the blood flow circuit 141 to allow water to flow continuously around the system. If the heater 72 is activated, the water passing through the system is continuously heated, e.g., to a temperature sufficient to disinfect the system.

[0086] 6 is a close-up view of the mixing circuit 25 in the example embodiment of FIG. 2. Water from the directing circuit 142 flows into the mixing circuit 25 by the action of a pump 180. In this embodiment, the pump 180 includes one or more pod pumps similar to those described above. In one embodiment, a portion of the water is directed through the mixing circuit 25 to the reagent component 49 for use in transporting a component such as, for example, the bicarbonate 28. In one embodiment, the sodium chloride and / or sodium bicarbonate 28 is provided in powder or granular form and mixed with water provided by the pump 180. Bicarbonate from the bicarbonate source 28 is delivered through a bicarbonate pump 183 to a mixing line 186, which also receives water from the directing circuit 142. Acid from the acid source 29 (which may be in liquid form) is also pumped through an acid pump 184 to the mixing line 186. The components 49 (water, bicarbonate, acid, NaCl, etc.) are mixed in mixing chamber 189 to produce dialysate, which then flows out of mixing circuit 25 to directing circuit 142. Conductivity sensors 178, 179 are positioned along mixing line 186 to ensure that as each component is added to the mixing line, it is added at the proper concentration. Because the volume pumped by water pump 180 and / or other pumps is directly related to the conductivity measurement, the volume measurement can be used as a cross-check on the composition of the dialysate being produced. This ensures that the composition of the dialysate remains safe, even if the conductivity measurement becomes inaccurate during treatment.

[0087] FIG. 7 is a perspective view of a hemodialysis system 5 incorporating various aspects of the present invention. According to one aspect of the present invention, the system 5 includes a dialysis unit 51 and a power module 52 shown joined together. In this embodiment, the dialysis unit 51 has a housing that contains components suitable for performing hemodialysis, such as a dialyzer, one or more pumps for circulating blood through the dialyzer, a dialysate source, and one or more pumps for circulating dialysate through the dialyzer. For example, the dialysis unit 51 can include a mixing circuit 25, a blood flow circuit 141, a balancing circuit 143, and a directing circuit 142, as described above. The dialysis unit 51 can also include all blood circuit and dialysate fluid connections necessary for operation of the system 5. Patient access and other connections can be exposed by opening a vertical parallel door 53 through a handle 54 at the front of the housing of the dialysis unit 51. In this embodiment, the dialysis unit 51 includes a control interface 55 (attached to the housing by a flexible cable in this embodiment) that can be used to control the operation of the dialysis unit 51. The control interface 55 includes a display screen with a touch-sensitive overlay, allowing touch control and interaction with a graphical user interface presented on the screen. The control interface 55 may also include other features such as push buttons, a speaker, a microphone for receiving voice commands, a digital camera, etc. The rear side of the control interface 55 may include a retractable "kickstand" (not shown) that allows the control interface 55 to be positioned on the housing of the dialysis unit 51. Provision of the retractable "kickstand" places the control interface 55 in a generally vertical position for proper viewing of the display screen. In other embodiments, the control interface 55 may include a tablet computer or a handheld electronic communication device, either of which may wirelessly communicate with a controller housed within the dialysis unit 51. Examples of wireless communication means may include wireless local area network technologies such as Bluetooth® technology or Wi-Fi® technology.

[0088] The housing of the power section 52 can include components suitable for providing operating power to the dialysis unit 51, for example, providing air / vacuum to the pumps, valves, and other components of the dialysis unit 51. As used herein, "pneumatic" refers to the use of air or other gas to move a flexible diaphragm or other member (air is used merely as an example, and in other embodiments, nitrogen (N 2 ), CO 2 (It should be noted that other control fluids, such as, for example, argon, water, oil, etc., may be used.) As noted above, the pumps and valves of the dialysis unit 51 are pneumatically powered, and thus the power section 52 may provide one or more sources of pneumatic pressure for use by the dialysis unit 51. In this manner, the dialysis unit 51 need not necessarily be configured to generate and / or store the necessary pneumatic power, but may instead rely on the power section module 52. The power section 52 may include one or more pneumatic pumps for generating the desired pneumatic pressure and / or vacuum, one or more accumulators or other devices for storing pneumatic power, valves, lines, and / or other devices for controlling air flow in the power section 52, and a controller having suitable components, such as a programmed general-purpose data processor, memory, sensors (e.g., for sensing pressure, temperature, etc.), relays, actuators, etc.

[0089] In one embodiment, pneumatic power (e.g., air under suitable pressure / vacuum) can be provided by the power section 52 through one or more supply tanks or other pressure sources to the dialysis unit 51. For example, if two tanks are used in the power section 52, one supply tank can be a positive pressure reservoir, in one embodiment, with a set point of 750 mmHg (gauge pressure) (1 mmHg is approximately 133.3 Pascals). The other supply tank can be a vacuum or negative pressure reservoir, in one embodiment, with a set point of -450 mmHg (gauge pressure). This pressure difference can be utilized, for example, between the supply tank pressure and the required pod pump pressure, to allow for precise control of the variable valves for the pod pumps. The supply pressure limit can be set based on the maximum pressure that can be set for the patient blood flow pump plus a margin to provide sufficient pressure difference for control of the variable valves. Thus, in one embodiment, two tanks are used to provide pressure and control fluids for all of the functions of the dialysis unit 51.

[0090] In one embodiment, the power section 52 may include two independent compressors serving the supply tanks. The pressure in the tanks may be controlled using any suitable technique, such as, for example, a simple "bang-bang" controller (i.e., a controller that has two states: on or open and off or closed) or a more sophisticated control mechanism, depending on the embodiment. As an example of a bang-bang controller, for a positive tank, if the actual pressure is less than the set point, the compressor serving the positive tank is turned on. If the actual pressure is greater than the set point, the compressor serving the positive tank is turned off. The same logic can be applied to control the vacuum tank and vacuum compressor, except the sign of the set point term is reversed. If the pressure tank is not regulated, the compressor is turned off and the valve is closed.

[0091] Tighter control of the pressure tanks can be achieved by reducing the size of the hysteresis band, but this may result in a higher cycling frequency of the compressor. If very tight control of these reservoirs is required, the bang-bang controller can be replaced with a proportional-integral-derivative ("PID") controller using a pulse-width modulated ("PWM") signal on the compressor. Other control methods are possible.

[0092] Other pressure sources may be used in other embodiments, and in one embodiment, two or more positive pressure sources and / or two or more negative pressure sources are used. For example, two or more positive pressure sources may be used that provide different available positive pressures (e.g., 1000mmHg and 700mmHg) to minimize leakage. For example, a high positive pressure may be used to control a valve while a low positive pressure may be used to control a pump. This helps to limit the amount of pressure that may be delivered to the dialyzer or patient and prevents the actuation of a pump from overpowering the pressure applied to an adjacent valve. A non-limiting example of a negative pressure is -400mmHg. In one embodiment, the negative pressure source may be a vacuum pump and the positive pressure pump may be an air compressor.

[0093] In one embodiment, the power section 52 comprises a housing capable of housing components such as those shown in FIG. 7a. In this example, the pump and air pressure storage assembly is configured to fit within the power section 52 and comprises a positive pressure pump 60, a negative pressure or vacuum pump 61, a high positive pressure reservoir 62, a low positive pressure reservoir 63, a negative pressure reservoir 64 and a dehumidifier or "chiller" section 65. The high positive pressure reservoir 62 can store air at a pressure of, for example, about 1000 mmHg to 1100 mmHg or more, and the low positive pressure reservoir 63 can store air at a pressure of, for example, about 700 mmHg to 850 mmHg. Pressurized air generated by the positive pressure pump 60 can be used to fill the reservoir 63 by interposing a pressure regulator (not shown) between the outlet of the pump 60 and the inlet of the reservoir 63.

[0094] A cooler 65 or other suitable dehumidifier may be interposed between the outlet of the positive pressure pump 60 and the inlet of one or more positive pressure reservoirs 62 and / or 63. Dehumidification of the pressurized air may prevent moisture condensation inside the pneumatic lines or manifold passages and valves driven by the positive pressure reservoirs 62 and / or 63. As shown diagrammatically in FIG. 7b, the cooler 65 may comprise a metal coil tubing 66 through which air from the compressor 60 passes and where water may be condensed from the compressed air. A cooling element 67 may separate the compressed air coil from a heat exchanger 68 through which ambient air may be drawn, warmed, and exhausted by a fan 69. The heat exchanger rejects heat to the ambient environment and a water trap 70 separates the condensed water from the compressed air. The dry compressed air can then be stored in reservoir 62 (or stored in low pressure reservoir 63 through a pressure regulator) or delivered to downstream equipment 71, such as a valved air pressure manifold. Cooling element 67 can be a commercially available powered Peltier element, such as Tellurex, Inc. element model C1-34-1604. Figure 7c shows an example of how cooler 65 can be positioned and configured to fit within the confines of power section 52.

[0095] Further, the power unit 52 may be selectively connectable to the dialysis unit 51, for example, so that it can be replaced with a different power unit 52. For example, the dialysis unit 51 may be configured to work with different types of power units 52, such as a power unit 52 that uses electrical power to generate air power and a power unit 52 that uses stored air power (e.g., pressurized air stored in one or more high-pressure tanks). Thus, the power unit 52 may be replaced with another unit 52 in case of a malfunction or other requirement. For example, it may be desired to use the system 5 in an area where noise generation is unacceptable, such as when nearby people are sleeping. In this case, it may be desirable to use a power unit 52 that uses stored air power rather than a unit 52 that generates air power by operating a pump or other noise-generating equipment. As shown in FIG. 8, the power unit 52 may be disconnected from the dialysis unit 51 by operation of a handle 521. For example, the handle 521 may be turned to unlock the power unit 52 from the dialysis unit 51, severing not only the mechanical connection between the housings, but also the power and / or communication connection between the two. An interface (not shown) between the dialysis unit 51 and the power section 52 allows air power (from the power section 52 to the dialysis unit 51), as well as power, control communications, etc., to be passed between the units. The dialysis unit 51 may have connections for power (e.g., standard 115V, 15 Amp power at a household electrical outlet), external communications (Ethernet or any other suitable connection for communications), water, etc. The dialysis unit 51 provides power or other connections to the power section 52, if desired.

[0096] The dialysis unit 51 may include a controller that controls the flow of control fluid to the various components of the system 5 and performs other desired functions. In one embodiment, the control fluid is held at various pressures in the various tubes or lines. For example, some control fluids are held at positive pressure (i.e., greater than atmospheric pressure) and other control fluids are held at negative pressure (below atmospheric pressure). Also, in one embodiment, the controller may have components that are held separate from the various fluid circuits. This configuration has several advantages. For example, in one embodiment, the fluid circuits of the dialysis unit 51 are heated to disinfection temperatures and / or exposed to relatively high temperatures or other harsh conditions (e.g., radiation) to perform disinfection, while not being exposed to harsh conditions like the electronic components of the controller, which may be kept separate by an insulating barrier (e.g., a "fire wall") or the like. That is, the dialysis unit housing may include two or more compartments, for example a compartment having electronics or other components that are sensitive to heat or other conditions, and a compartment having fluid circuit components that are heated or otherwise treated for disinfection.

[0097] Thus, in some embodiments, the system 5 includes a "cold" section (not heated) and a "hot" section that can be heated, for example for disinfection. The cold section can be insulated from the hot section by insulation. In one embodiment, the insulation is a molded foam insulation, and in another embodiment includes any type of insulation, such as, but not limited to, spray insulation, air gaps, insulation cut from sheets, etc. In one embodiment, the cold section includes a circulation system, such as, for example, a fan and / or a grid that can move air in and out of the cold box. In one embodiment, the insulation can extend to cover the access points to the "hot" section, such as doors, ports, gaskets, etc. For example, when the "hot" section is sealed, the insulation can completely cover the "hot" section in one embodiment.

[0098] Non-limiting examples of components that may be in the "cold" section include power supplies, electronics, power cables, air controls, etc. In one embodiment, at least a portion of the fluid traveling to and from the "hot" section passes through the "cold" section. However, in other cases, the fluid may flow to the "hot" section without passing through the "cold" section.

[0099] Non-limiting examples of components that may be in the "hot" section include the cassette (if present), fluid lines, temperature and conductivity sensors, blood leak sensors, heaters, other sensors, switches, emergency lights, etc. In one embodiment, some electronic components may also be included in the "hot" section. Examples include, but are not limited to, heaters. In one embodiment, a heater may be used to heat the hot box itself in addition to the fluid. In some embodiments, a heater 72 heats the entire "hot" section until it reaches the desired temperature.

[0100] According to one aspect of the invention, the housing of the dialysis unit 51 can be provided with vertical parallel doors that can be opened to expose all the mechanical interface points for the blood flow circuit connections and the dialysate circuit connections, i.e., all the connection points for the patient blood connections and the acid / bicarbonate connections that a user must make to use the dialysis unit 51. FIG. 9 is a front view of the dialysis unit 51 with the vertical parallel doors 53 in a closed state. In this configuration, the doors 53 can block access to the connection points for the patient blood connections and the acid / bicarbonate connections and seal the inside of the unit housing to allow for the conservation of heat suitable for disinfection. The seal provided by the doors 53 can be airtight to prevent or substantially inhibit air exchange between the interior and exterior environments of the housing, or it can be somewhat degraded to maintain disinfection effectiveness.

[0101] In this embodiment, the door 53 is connected to the housing of the dialysis unit 51 by a double hinge structure such that the door 53 can be opened in two different open positions. Figures 10-13 show the door 53 in a first open position. In this position, the door 53 exposes all user connections for the blood circuit connections and the dialyzer circuit, including the dialyzer 14 itself and reagent materials such as consumable acid / bicarbonate materials. This position also exposes other features such as a holder 531 for an acid / bicarbonate container (not shown) and a hook 532 that can be used to hold any suitable element such as a control interface 55, which can hook its handle onto the hook 532 (see Figure 7 which shows the hook 532 on the front of the left door 53 which can be opened to accommodate the control interface 55 or other elements). The holder 531 in this embodiment can be folded from the position shown (i.e., folded to extend horizontally from the door 53 and into a recess in the door 53). The holder 531 has a "C" shaped receiving portion that receives and holds the acid / bicarbonate container, but can of course be of any suitable shape or other configuration.

[0102] 14-16 show the doors 53 in a second open state in which the hinge plate 533 of each door 53 pivots outwardly away from the dialysis unit housing 51. In this embodiment, the hinge plates 533, which extend vertically along substantially the entire height of the dialysis unit housing 51, are pivotally attached to the doors 53 at a first outer end and to the dialysis unit housing 51 at a second inner end (it is understood that the hinge plates 533 can be configured differently, e.g., disposed and / or positioned at the top and bottom of the doors 53 as found in many refrigerator door constructions, and each plate 533 can have two or more portions that are separated vertically from one another). The magnets 534 mounted on the hinge plates 533 interact with corresponding magnets (or other suitable components such as steel elements) mounted on the dialysis unit housing 51 to attract the hinge plates 533 towards the dialysis unit housing 51, thereby holding the hinge plates 533 in the position shown in Figures 10-13 (it will be appreciated that the magnets 534 can be located on the unit housing and the hinge plates 533 can have suitable elements (such as pieces of steel) mounted to the magnets 534). Because the door 53 in this embodiment also includes magnets mounted on the hinge plates 533, when the door 53 is opened to a first state as shown in Figures 10-13, the magnets interact with corresponding magnets in the hinge plates 533 to assist the door 53 in being in an open position relative to the hinge plates 533. Additionally, these magnets assist in maintaining the relative position of the door 53 and the hinge plates 533 when the hinge plates 533 are opened to a second state as shown in Figures 13-16.

[0103] In this exemplary embodiment, magnets are used as part of the retaining member to help maintain the door 53 and / or hinge plate 533 in a particular open or closed state, however, other structures of the retaining member are possible. For example, the hinge connection between the door 53 and the hinge plate 533 and / or the connection between the hinge plate 533 and the housing 51 may be a detent structure that serves to resiliently hold the door 53 or hinge plate 533 in a particular position relative to the other part (the hinge plate or the housing). In another embodiment, one or more springs may be used to help hold the door 53 in an open position relative to the hinge plate 533. In yet another embodiment, the hinge plate 533 may be a frictional or static fit with a portion of the housing 51 that attempts to hold the hinge plate 533 in a closed position (proximate the housing). Thus, the retaining member that serves to hold the door 53 in a particular position relative to the hinge plate 533 and / or the hinge plate 533 in a particular position relative to the housing 51 can take one of a number of possible structures.

[0104] According to another aspect of the invention, opening the door towards the dialysis unit housing exposes all of the user connections for the blood circuit connections and dialysate fluid connections necessary for the operation of the system 5. For example, as shown in FIG. 17, when the door 53 is in an open state (either the first or second open state), the front panel 511 of the dialysis unit 51 can be exposed. In this embodiment, the front panel 511 carries several elements or connection points that the user must access. For example, the dialyzer 14, which must be replaced periodically, is mounted on the front panel 511. The dialyzer 14 must be connected to the blood flow circuit 141 as well as the balance circuit 143. Additionally, a connection point 512 for the acid / bicarbonate source 49 is located at the bottom end of the front panel 511. At this connection point 512, the user can connect to a source of consumable reagent components 49 that the dialysis unit 51 uses in creating dialysate. An occluder 513 is also mounted on the front panel 511. The closure 513 receives the tubing of the blood flow circuit and controls the open / closed state of the tubing based on system operation. The function of the closure 513 is described in more detail in U.S. Patent Application Serial No. 12 / 198,947, filed August 27, 2008 (Attorney Docket No. D0570.70020US00(G28)) and will be described in more detail below. In summary, the closure 513 allows flow through the arterial and venous lines of the blood flow circuit unless there is a system problem such as a leak, pump failure, overpressure condition, etc. In that case, the closure 513 automatically closes the blood lines to prevent flow to or from the patient. Exposed on the front panel 511 are blood line connection points 514 that connect the arterial and venous blood lines 203, 204 of the blood flow circuit 141 with the directing circuit 142 (the blood flow circuit 141 can be connected to the directing circuit 142 as described with reference to Figures 2 and 3). This connection is typically made at the end of treatment so that the system can clean and sterilize the blood flow circuit 141. The front panel 511 also has a set of control ports 515 that mate with corresponding control ports on the blood pump portion of the blood flow circuit 141.The control port 515 provides controlled levels of air pressure and / or vacuum to control the open / closed state of the valves and to power the pumps in the blood flow circuit 141 .

[0105] In another embodiment of the invention, FIG. 17A shows a perspective view of a control port assembly 615 to which the blood pump assembly 13 can be mounted and to which the fluid control ports of the blood pump assembly 13 can be connected. For example, a control port 616 for controlling the operation of the valves of the blood pump assembly 13 and a control port 617 for controlling the operation of the pumps of the blood pump assembly 13 are shown. A latch member or other engagement device can be provided on one or more surfaces of the control port assembly 615 or within the control port assembly 615, or adjacent to or within the location of the control port assembly 615 on the front panel assembly 511 to secure the blood pump assembly 13 to the control port assembly 615 (in the illustrated example, the control port assembly 615 can be reversibly mounted to the front panel assembly 511 via a retention tab 619). Alternatively, or in addition, a breakaway or other removal feature for the blood circuit assembly can be provided to facilitate removal of the blood pump assembly or other parts of the blood circuit assembly from the front panel 511. For example, a pair of cassette latch and removal assemblies can be mounted on both sides of the control port assembly 615. In the embodiment of FIG. 17A, the blood circuit assembly engagement device comprises latch or retainer members 618a and 618b pivotally mounted to the sides of the control port assembly 615. Preferably, the pivot connections of the latch members 618a and 618b (e.g., pivot connection 620) are biased by appropriately positioned springs to rotate the latch members 618a and 618b toward each other and toward the surface of the control port assembly 615 so that they can maintain contact with an edge or other portion of the blood pump assembly 13 (shown in cross section in FIG. 17B) mounted to the control port assembly 615. This is more clearly shown in FIG. 17B, which is a top cross-sectional view of the control port assembly 615 with the blood pump assembly 13 mounted thereon. The latch member 618b is shown in its normally biased position in FIG. 17B, securing the outer edge of the blood pump assembly 13 relative to the control port assembly 615.Meanwhile, the latch member 618a is shown in a partially retracted position to allow the blood pump assembly 13 to be partially isolated from the control port assembly 615. In a fully retracted position (not shown), the latch members 618a or 618b clear a leading edge of the blood pump assembly 13 to allow the blood pump assembly 13 to be removed from or installed or mounted to the control port assembly 615.

[0106] 17A and 17B, in addition to the latch or retainer members 618a and 618b that can help retain the blood pump assembly 13 to the control port assembly 615, a separation assist member (or ejector element or member) 622a or 622b can also be included to assist a user in separating the blood pump assembly 13 from the control port assembly 615 and lifting it from the control port assembly 615. The separation assist member 622a or 622b can be pivotally mounted to the front panel assembly 511 in a position suitable for the contact portion 624a or 624b of the separation assist member 622a or 622b to contact an edge of the lower surface 113a of the blood pump assembly 13 when the separation assist member 622a or 622b is rotated outward to help lift it from the control port assembly 615. The engagement device may comprise an actuator for actuating the retainer member 618 and / or the ejector element 622, such as a thumb or finger contact element 626a or 626b that the user may press laterally to pivot the separation assist member 622a or 622b outwardly to engage the contact portion 624a or 624b with the lower surface 113a of the blood pump assembly 13. Preferably, a spring 628 may be included near the pivot connection of the separation assist member 622a or 622b and appropriately positioned to bias the separation assist member 622a or 622b to move the contact portion 624a or 624b out of contact with the lower surface 113a of the blood pump assembly 13. In this manner, no inherent force from the separation assist member 622a or 622b is acting to push the blood pump assembly 13 away from the control port assembly 615. In another preferred embodiment, the separation assist member 622a or 622b can be pivotally mounted to the latch member 618a or 618b, as shown in Fig. 17A. In this embodiment, a user can separate the latch members 618a and 618b from contact with the leading edge or surface of the blood pump assembly 13 by engaging the separation assist member 622a or 622b with the underside 113a of the blood pump assembly 13 and simultaneously pushing the thumb or finger contact element 626a or 626b outward once.Thus, by pushing one or more actuators, such as a single element 626a or 626b, outward, the blood pump assembly 13 can be alternately attached and secured to the control port assembly 615 or detached from the control port assembly 615, facilitating installation and / or removal of the blood pump assembly 13.

[0107] 17C shows another embodiment of the blood circuit assembly engagement device, which in this embodiment includes a pair of blood pump cassette retainer and ejector elements. In this embodiment, the cassette retainer element 630 includes a contact member 632 that contacts the ejector (or separation aid) element 634. In the retracted state, the ejector element 634 is disposed in a recessed area 636 of the blood pump pod recess 638 of the control port assembly 640. As the retainer element 630 pivots outward (in the direction of the arrow in FIG. 17C), the contact member 632 presses against the proximal end 642 of the ejector element 634, which then rotates about the pivot axis 644, causing the distal end 646 of the ejector element 634 to rise out of the recess 636 and engage the rigid rear wall of the working chamber of the mounted pump cassette disposed in the blood pump pod recess 638. 17D and 17E show isolated views of the engagement device with the ejector element 634 in a retracted position (FIG. 17D) and an extended position (FIG. 17E). In FIG. 17D, the retainer element 630 is in the retaining position, the retainer element 648 is rotated inwardly toward the center of the control port assembly 640, and the ejector element 634 is in the retracted position with the proximal portion 642 raised and the distal portion 646 depressed. In FIG. 17E, the retainer element 630 is in the released position, the retainer element 648 is rotated outwardly away from the center of the control port assembly 640, and the ejector element 634 is in the raised position with the proximal portion 642 lowered by the contact member 632 and the distal portion 646 raised out of the recess 636 to eject a cassette loaded into the control port assembly 640. Thumb rest (actuator) 650 is shaped to allow a user to apply an outward force to release the cassette, conveniently by placing one thumb on each of the opposing latch members 630 in the completed assembly as shown in Figure 17C. In one embodiment, the retainer element 630 rotates about an axis formed by a pinion 652 with a spring 654 biased in a latching or retaining direction to help keep the cassette secured and mounted to the control port assembly 640.FIG. 17F shows a front view of the blood pump cassette 1000 (which is part of the blood circuit assembly) mounted on a panel of a dialysis unit, such as the exposed front panel 511. FIGS. 17G and 17H show cross-sectional views of the blood pump cassette 1000 along lines 17G-17G and 17H-17H, respectively, with the cassette 1000 properly attached to the control port assembly 640. FIG. 17G shows the relationship between the contact members 632, the ejector element 634, and the rigid rear wall 658 of the pump actuation chamber of the cassette 1000. The ejector elements 634 are shown in their fully retracted positions in their respective recessed areas 636 to allow the pump cassette 1000 to be fully attached. FIG. 17H shows the relationship between the retainer element 648 and the front plate 656 of the cassette 1000. In this case, the retainer element 648 is juxtaposed with the front plate 656 to secure the cassette 1000 onto the control port assembly 640 .

[0108] FIG. 17I shows a front view of the blood pump cassette of FIG. 17F in the process of being separated from the panel 511 of the dialysis unit. FIGS. 17J and 17K show cross-sectional views of the blood pump cassette 1000 with the cassette 1000 partially lifted out of engagement with the control port assembly 640. FIG. 17J shows the relationship between the contact member 632, the ejector element 634, and the rigid rear wall 658 of the pump actuation chamber of the cassette 1000. In this case, the distal end 646 of the ejector element 634 contacts the cassette 1000 to lift it from its fully installed position in the control port assembly 640. FIG. 17K shows the relationship between the retainer element 648 and the front plate 656 of the cassette 1000. In this case, the front plate 656 has been lifted above the retaining surface of the retainer element 648.

[0109] Also exposed on the front panel 511 of FIG. 17 is a user control panel 510. The user control panel 510 includes one or more buttons that allow the user to bypass the graphical user interface on the control interface 55 during hemodialysis and provide an alternative way to control certain functions (e.g., critical functions). This could be of great importance, for example, if the control interface 55 were to fail during a dialysis treatment session. Non-limiting examples of critical functions are a "Stop Dialysis" or "Pause Dialysis" command and a "Dialysis Solvent Injection" command.

[0110] According to this embodiment and another aspect of the invention, the blood flow circuit 141 is formed as a blood circuit assembly that is removable from the front panel 511 of the dialysis unit 51, and FIG. 17 does not show the arterial and venous lines 203, 204 for the blood flow circuit 141 because the blood circuit assembly is not mounted to the front panel 511 in FIG. 17. FIG. 18 shows a front view of the blood circuit assembly 17 of this embodiment along with the dialyzer 14. The blood circuit assembly 17 includes the various components described above, for example with reference to FIG. 3, mounted on a blood circuitry tray 171. The arterial and venous lines 203, 204 (e.g., including lengths of flexible silicone tubing) terminate in blood line connectors that are configured to provide a plug-in or press-fit type connection with the blood line connection point 514, as well as a threaded connection for use with common patient access points (e.g., luer type patient access connectors), according to one aspect of the invention. The arterial line 203 leads to an inlet present on the top of the blood pump 13, which includes two pod pumps 23, valves, and other components that control blood flow. The blood pump 13 is associated with an air filter 81, an anticoagulant pump 80 (not shown), and an anticoagulant source 11 (such as a vial of heparin) (more details regarding the blood pump 13 of this exemplary embodiment are found in U.S. patent application Ser. No. 11 / 871,680, filed Oct. 12, 2007, entitled "Pumping Cassette," U.S. patent application Ser. No. 11 / 871,712, filed Oct. 12, 2007, entitled "Pumping Cassette," U.S. patent application Ser. No. 11 / 871,787, filed Oct. 12, 2007, entitled "Pumping Cassette," and U.S. patent application Ser. No. 11 / 871,787, filed Oct. 12, 2007, entitled "Pumping Cassette"). No. 11 / 871,793, filed Oct. 12, 2007, entitled "Cassette System Integrated Apparatus," and U.S. patent application Ser. No. 11 / 871,803, filed Oct. 12, 2007, entitled "Cassette System Integrated Apparatus."Blood output from blood pump 13 (outlet located at the bottom of pump 13) enters dialyzer 14 inlet (located at the top of dialyzer 14) and exits the dialyzer (dialyzer blood outlet located at the bottom of dialyzer 14) into the inlet of air trap 19. The outlet of air trap 19 is connected to venous blood line 204. Connections to the inlet and outlet blood ports of dialyzer 14 are made by typical threaded type connections.

[0111] FIG. 18a shows a perspective view of a blood pump 13 with another embodiment of a vial receiver or vial holder 1206 that holds or rests a vial of medication 11 (such as an anticoagulant) on a hollow spike 1208 that is in fluid communication with the pump 80 (schematically shown in FIG. 3) of the blood pump 13. In this embodiment, a flexible upper arm 1210 helps to hold the body of the vial 11 in place and can flex to accommodate vials of various sizes. A lower arm 1212 helps to align the inverted top of the vial 11 with the spike 1208 to prevent the vial 11 from protruding at an angle relative to the inverted top of the vial 11. Protruding the top of the vial 11 substantially vertically can help to avoid leakage of fluid from within the vial 11 around the outside of the spike 1208.

[0112] According to another aspect of the invention, the air trap 19 is placed in the blood flow path after the blood leaves the dialyzer until it is returned to the patient. In one embodiment, the air trap 19 can have a spherical or spheroidal container (i.e., a container with a generally spherical inner wall), an inlet port located near the top and offset from the longitudinal axis of the container, and an outlet at the bottom of the container (the longitudinal axis of the container is vertically oriented passing through the "upper" and "lower" poles of the generally spherical container). The inlet port is offset from the longitudinal axis (in this case, set back toward the tray 171), and blood is introduced into the container in a direction generally perpendicular to the longitudinal axis of the container and generally tangential to the spherical inner wall of the container. The curved shape of the trap's inner wall induces the blood to circulate along the inner wall as it is drawn by gravity (e.g., in a spiral) to the lower end of the container, facilitating the removal of air bubbles from the blood. Air present in the blood leaving the outlet of the dialyzer 14 enters the upper end of the air trap 19 and remains at the upper end of the container while the blood flows out of the outlet at the lower end into the venous blood line 204. By locating the inlet port near the top of the trap 19, blood can be circulated through the trap with minimal or no air remaining in the container (as a "wide open" air trap). Because of the regular circulation of blood through the trap, it is advantageous to avoid contact between the air and the blood. By locating the inlet port at or near the top of the container, the fluid flow through the blood tube can be reversed (i.e., flowing from the bottom to the top of the trap 19 and exiting the inlet port of the trap 19) to remove most or all of the air present in the trap from the trap.

[0113] In one embodiment, a self-sealing port, such as a split septum or membrane or other structured self-sealing stopper, is placed at the top of the trap to allow air to be drawn from the container (e.g., by a syringe). The blood side of the self-sealing membrane can be placed nearly flush with the inside top of the trap to facilitate cleaning of the self-sealing port during disinfection, for example, by reversing the flow in the air trap with dialysate or other cleaning fluid. The inlet, outlet, and interior walls of the container and the self-sealing port can also be configured to substantially eliminate stagnant areas, i.e., there are few or no areas where blood can stagnate or clot. The self-sealing port can serve as a blood sampling site and / or allow the introduction of liquids, drugs, or other compounds into the blood circuit. When needle access is contemplated, a sealing rubber type stopper can be used. A self-sealing stopper using a split septum allows sampling and fluid delivery using a needleless system.

[0114] FIG. 19 shows an organizing tray 171 for blood circuit assemblies 17 without various blood circuit assembly 17 components. According to one aspect of the invention, the organizing tray 171 includes a handle 172 (in this embodiment, a finger pull) that a user can grasp when mounting / removing the blood circuit assembly 17 to / from the front panel 511. An opening 173 is provided on the inside of the handle 172 so that a spring tab on the front panel 511 can pass through the organizing tray 171 and / or the cassette of the blood pump 13 to engage the blood circuit assembly 17 and hold the blood circuit assembly 17 in place on the front panel 511. According to another aspect of the invention, the organizing tray 171 includes blood line engagement members 174 each having a C-shaped recess or other hole through which a corresponding blood line 203, 204 passes (here, "hole" includes a recess as shown in FIG. 19, a through hole with a continuous wall, e.g., made by a drill, or other suitable opening). More specifically, blood line engaging members 174 are used when loading blood lines 203, 204 into closure 513. In summary, when loading blood lines 203, 204 into closure 513, the blood lines 203, 204 must be pulled downwards (to reduce the outer diameter of the lines) and stretched while being pushed horizontally into a slot in closure 513. Blood line engaging members 174 function to resist the downward pull on blood lines 203, 204 (e.g., each line 203, 204 can have a stop ring on each engaging member 174 so that it cannot be pulled through a recess in engaging member 174) and to allow the user to push engaging member 174 inward to position lines 203, 204 into the closure slot. Because the engagement member 174 is integrally formed with the organized tray 171, a "living hinge", i.e., a relatively flexible portion of the organized tray, is disposed between the engagement member 174 and the main body of the organized tray 171. This structure allows the engagement member 174 to be pushed inwardly relative to the organized tray 171 as the connection between the engagement member 174 and the main body of the organized tray flexes.

[0115] FIG. 20 is a rear view of the blood circuit assembly 17 with the organization tray 171 removed. This view shows the rear of the blood pump 13 exposing the control ports. These control ports mate with corresponding ports 515 on the front panel 511 (see FIG. 17) so that pneumatic control (e.g., appropriate air pressure or vacuum) is applied to the pumps and valves to control their operation and flow through the blood circuit assembly 17. FIG. 20 also shows the offset of the inlet port of the air trap 19; that is, the inlet port at the top of the air trap 19 is located behind the longitudinal axis of the generally spherical container portion of the air trap 19.

[0116] Figures 20A and 20B show exploded perspective views of another embodiment of a blood pump cassette 1000. Figure 20A shows a front exploded perspective view of the cassette 1000 having a rear (actuation) plate 1001 with tubing organization formed therewith in a single molded piece of material. Figure 20B shows a rear exploded perspective view of the cassette 1000 of Figure 20A. The cassette 1000 shown in Figures 20A-20D can be used as an alternative to the cassette 13 of Figure 18A and organization tray 171 of Figure 19, combining many of the functions of these components and substantially reducing the cost and complexity of manufacturing and assembling them.

[0117] The cassette 1000 comprises a back plate 1001 which forms the rigid outer walls of the working chambers of the various valves and pumps, a middle plate 1002 which holds the various valve and pump diaphragms and helps to form the various flow paths in the cassette 1000, and a front plate 1003 which forms the rigid outer walls of some of the fluid chambers of the various valves and pumps of the cassette 1000. The cassette 1000 further comprises an optional protective cover 1004 which can be attached to the front side of the back plate 1001. The protective cover 1004 can include a retention arm which can be used for later mounting to a vial holder 1037, which holds a vial. The protective cover 1004 can temporarily hold either an empty or a filled vial before the vial is inserted into the vial holder 1037 for use during a procedure. That is, the vial can be coupled to a vial holder 1037 having a hollow spike that places the vial within the vial holder 1037 in fluid communication with a fluid port 1038 in the front plate 1003. The vial can be filled with, for example, an anticoagulant used during dialysis, or the vial can be empty and used during cleaning and disinfection procedures either before or after dialysis treatment.

[0118] The cassette 1000 includes fluid flow pumps 1013 and 1014 that move fluid through the fluid flow side of the cassette 1000. That is, the cassette 1000 includes a left pump 1013 and a right pump 1014 that pump fluid, which may be blood in the case of a hemodialysis machine. The pumps 1013 and 1014 (also referred to herein as pod pumps) may be actuated by a controlled fluid, such as air, liquid, gas, or other fluid that enters the cassette 1000 through a port in the back plate 1001. The left pod pump 1013 includes a rigid chamber wall 1005 formed in the front (or top) plate 1003, a rigid chamber wall 1008 formed in the back (or bottom) plate 1001, a hole 1006 formed in the middle plate 1002, and a flexible membrane 1007 that may be deflected between the rigid chamber walls 1013 and 1008. The space between the rigid chamber wall 1013 and the flexible membrane 1007 forms the fluid or blood side (i.e., the fluid chamber) of the left pump 1013, and the space between the flexible membrane 1007 and the rigid chamber wall 1008 forms the pneumatic side (i.e., the control chamber) of the left pump 1013. Similarly, the right pod pump 1014 comprises a rigid chamber wall 1009 formed in the top plate 1003, a rigid chamber wall 1012 formed in the bottom plate 1001, a hole 1010 formed in the middle plate 1002, and a flexible membrane 1011 that can deflect between the rigid chamber walls 1009 and 1012. The space between the rigid chamber wall 1009 and the flexible membrane 1011 forms the fluid or blood side (i.e., the fluid chamber) of the right pump 1009, and the space between the flexible membrane 1011 and the rigid chamber wall 1012 forms the pneumatic side (i.e., the control chamber) of the right pump 1014.

[0119] Each of the pod pumps 1013 and 1014 can include a pair of membrane-based inlet / outlet valves with a fluid flow compartment formed from the top plate 1003 and a control compartment formed from the bottom plate 1001. The valves can be actuated by applying positive or negative fluid (e.g., air) pressure to the respective flexible membranes through a control port in the bottom plate 1001. The fluid valves can be opened and closed to direct fluid flow when the pod pump is pumping. Fluid can be pumped forward or backward depending on the sequencing of valve actuation in conjunction with actuation of the pumps associated with those valves. Non-limiting examples of pod pumps are described in U.S. patent application Ser. No. 11 / 787,212, filed Apr. 13, 2007, entitled "Fluid Pumping Systems, Devices and Methods," which is incorporated herein by reference. Pod pumps 1013 and 1014 can be operated in any suitable manner, eg, synchronously, asynchronously, in phase, out of phase, etc., with fluid flow in either direction.

[0120] For hemodialysis applications, in one embodiment, an anticoagulant (e.g., heparin, or any other anticoagulant known to one of skill in the art) can be mixed with the blood within the blood flow cassette 1000. For example, the anticoagulant can be contained in a vial (or other source of anticoagulant, such as a tube or bag), and the blood flow cassette 1000 may be capable of accepting an anticoagulant vial with a vial holder 1037 (in one embodiment, comprising a needle or hollow spike) that can pierce the seal of the vial. The spike can be formed from plastic, stainless steel, or other suitable material, and in one embodiment, can be a sterilizable material, e.g., the material may be capable of withstanding high enough temperatures and / or chemical exposure to sterilize the material. As an example, the spike can be used to pierce the seal of the vial, allowing the anticoagulant to flow into the blood flow cassette 1000 and mix with the blood in the blood flow path. In other cases, the vial can be filled or partially filled with water or dialysis fluid during a cleaning, disinfecting, or priming procedure.

[0121] A third pump 1015 in the cassette 1000, which in one embodiment may act as a metering pump, may be used to control the flow of medication (such as an anticoagulant) from an attached vial into a fluid path in the cassette 1000. The metering pump 1015 may be the same or different design as pumps 1013 and 1014. For example, the metering pump 1015 may be a pod pump and may be actuated by a control fluid such as air. For example, as shown in FIGS. 20A-20D, the metering pump 1015 may include a rigid chamber wall 1015 formed in the back plate 1001, a rigid chamber wall 1018 (see FIG. 20B) formed in the middle plate 1002, and a flexible diaphragm 1015 that divides the pod into a fluid compartment or chamber and a control compartment or chamber. Valves 1028, 1029, 1030 can be connected to fluid flow paths joining in various combinations fluid port 1038, vent port 1019, fluid flow paths to or from a first or second pump (such as pump 1013), and fluid flow paths to or from metering pump 1015. Thus, the flow of a drug (e.g., an anticoagulant) or other fluid from a loaded vial into a primary fluid flow path in cassette 1000 can be controlled by metering pump 1015, which can periodically introduce air from vent port 1019 through port 1038 into the loaded vial to equalize the pressure in the loaded vial with ambient pressure as the drug or other fluid is withdrawn from the vial.

[0122] The cassette 1000 may also include an air vent connected to the port 1019. Air may be introduced into the flow path of the metering pump 1015 to equalize the pressure in the loaded vial with the ambient air. In this case, the valve 1029 closes off the flow between the metering pump 1015 and the main flow path of the first pump 1013 (or the second pump 1014). In one embodiment, the metering pump 1015 may also introduce air into the main flow path of the first pump 1013 or the second pump 1014 so that the system controller can control the emptying of the blood or fluid carrying components of the system.

[0123] Pod pumps 1013 and 1014 include raised channels 1020 and 1021, respectively, in chambers 1005 and 1009. Raised channels 1020 and 1021 allow fluid to continue flowing through pod pumps 1013 and 1014 after diaphragms (i.e., flexible membranes) 1007 and 1011 reach the end of their stroke.

[0124] The cassette 1000 comprises a number of valves 1022, 1023, 1024 and 1025 formed in the back plate 1001. The actuation (or pneumatic) sides of the valves 1022-1025 and 1028-1030 are formed from the bottom plate 1001 and have corresponding actuation ports for the entry or exit of control (e.g. pneumatic) fluid. A number of diaphragms 1026 and 1027 mounted on the middle plate 1002 complete the valves, and diaphragms 1007, 1011 and 1016 complete the pod pumps 1013, 1014 and metering pump 1015. The metering pump 1015 is completed by diaphragm 1016. In a preferred embodiment, the valves are pneumatically actuated, so that when the valve diaphragm is pulled away from an adjacent hole in the middle plate 1002 liquid is drawn out and when the diaphragm is pushed towards the hole liquid is forced through it. Fluid flow is directed by appropriate sequencing of the opening and closing of valves 1022-1025 and 1028-1030.

[0125] The metering pump 1015 comprises three passages connected to a fluid chamber 1018 formed in the middle plate 1002. One passage allows air from the vent 1019 to be drawn into the metering pump 1015, a second passage allows air to be pushed into a spike / source container connected to the vial holder 1037, which also alternately draws liquid from a source container or vial, and a third passage allows liquid from the source container to be pushed by the metering pump 1015 into a main fluid line connected to the first pump 1013 (or pump 1014 in another embodiment). Valves 1028, 1029 and 1030 determine whether and in which direction the metering pump 1015 moves fluid or air.

[0126] 20C, an internal view of the bottom plate 1100 is shown. An inside view of the actuation / air chambers of the pod pumps 1008 and 1012, metering pump 1015 and valves 1022, 1023, 1028, 1025, 1029, 1030 and 1024 is shown. The pod pumps 1008 and 1012, metering pump 1015 and valves 1022, 1023, 1028, 1025, 1029, 1030 and 1024 are actuated by a pneumatic air source. Now referring to FIG. 20D, the outside of the bottom plate 1100 is shown. A source of control fluid (e.g., air under positive or negative pressure) is connected to this outside of the cassette. In one embodiment, tubes connect to various ports 1031. In other embodiments, the port 1031 is configured to plug into a control port assembly (eg, control port assembly 615 in FIG. 17A) on a front panel (eg, front panel 511 in FIG. 17) of the dialysis unit 51.

[0127] 20A-20D, various organization features are incorporated into the lower plate 1001. The lower plate 1001 includes an air trap retaining member 1032 having tube guides 1033 and 1034 formed therein. The tube guides 1033 and 1034 guide tubing to and from an air trap located within the air trap retaining member 1032. The lower plate 1001 also includes additional tube guides 1035 and 1039. The lower plate 1001 also forms a receptacle 1036 that receives an electrical connector that can be used in the device to monitor for disconnection of an arterial or venous line from a patient during treatment. FIG. 21 is a perspective view of the front panel 511 of a dialysis unit 51 having a blood circuit assembly 17 mounted thereon without the organization tray 171 (the blood circuit assembly 17 typically includes an organization tray 171, but the tray 171 is not shown in this example to more clearly show the components of the front panel 511). At the opposite end of the cassette of the blood pump 13, the front panel 511 has spring tabs 516 that flexibly extend forward of the blood pump cassette and / or organization tray 171 to hold the blood circuit assembly 17 in place. The tabs 516 can have barbs or other features that help hold the blood circuit assembly 17 in place. The spring tabs 516 are bent outward to release their hold on the blood circuit assembly 17 to allow removal. However, if no outward force is applied to the spring tabs 516, the tabs 516 remain engaged with the blood circuit assembly 17. FIG. 22 is a front view of the front panel 511 including the organization tray 171 of the blood circuit assembly 17. To remove the blood circuit assembly 17 from the front panel 511, the user places their thumb on the inside of the spring tabs 516 (the side closest to the blood pump 23) and bends the spring tabs 516 outward, away from the pump 23, while simultaneously placing their index finger behind the handle 172. This causes the spring tabs 516 to release the blood circuit assembly 17 , e.g., the puncture of the tabs 516 separates from the blood pump 13 and / or the organizing tray 171 .Of course, to remove the blood circuit assembly 17, other connections such as the connection to the dialyzer 14 and the blood line connection point 514 must be removed, and the lines 203, 204 must also be removed from the closure 513. When mounting the blood circuit assembly 17 to the front panel 511, the organization tray 171 can be properly aligned by grasping the handle 172, for example, so that the spring tabs 516 are aligned to pass through the openings 173 and the control ports of the cassette of the blood pump 13 are aligned with the corresponding ports 515 on the front panel 511. The blood circuit assembly 17 is then simply pressed into place, with the spring tabs 516 engaging the organization tray 171 and / or the blood pump cassette. Other connections can then be made, such as the connection to the dialyzer 14 and the attachment of the blood lines 203, 204 to the closure 513.

[0128] 21 also shows slots 517 that hold the blood lines 203, 204 for leading into the closure 513. The slots 517 form passages that are slightly smaller than the outer diameter of the blood lines 203, 204 so that the lines 203, 204 remain within the slots 517 after placement in the slots. This helps ensure proper association of the lines with the closure 513. Once the blood circuit assembly 17 is loaded onto the spring tabs 516, the user engages the blood lines 203, 204 with the slots 517 by extending the lines 203, 204 downward (with the engagement members 174 on the organization tray 171 engaging stop rings or other features on each line 203, 204 to resist downward pulling) and pushing the lines 203, 204 into the corresponding slots. The lines 203, 204 can be forced into place by pushing inward on the engagement members 174, which, as described above, are flexible and bend inwardly against the organization tray 171. The lines 203, 204 can then be threaded through the closure 513.

[0129] In accordance with another aspect of the present invention, the front panel 511 includes a blood line wrap feature around the periphery of the front panel 511. In this exemplary embodiment, the front panel 511 includes flanges 518 along the top edge and bottom corners of the front panel 511. This allows a user to wrap the blood lines 203, 204 around the periphery of the front panel 511 by placing the lines 203, 204 within the passageway formed by the flanges 518. The lines 203, 204 can be wrapped in a clockwise direction from a point near the bottom end of the dialyzer 14 to a point near the bottom right corner of the front panel 511. The blood lines 203, 204 can then be connected at a blood line connection point 514 to, for example, disinfect the fluid circulated through the blood lines 203, 204. As a result, the blood lines 203, 204 are properly held on the front panel 511, allowing easy access to other components on the front panel 511, and allowing a user to close the door 53 with little concern of pinching the blood lines 203, 204 between the door 53 and the dialyzer unit housing 51. Alternatively, the blood lines 203, 204 can be first connected at the blood line connection point 514 and then wrapped clockwise from a point near the bottom end of the dialyzer 14 to a point near the lower right corner of the front panel 511. This ensures that the blood lines are properly distributed along the flange portion 518 to the connection point 514. Vertical fences 519 can also be provided on the left and right sides of the front panel 511 to help hold the blood lines 203, 204 in the desired location away from the hinge plate 533 and other potential pinch points.

[0130] In another aspect, as shown in FIG. 21A, another embodiment of the front panel assembly 811 can include a modular drainage assembly (or drainage cassette) 815 having connection points 814 to which the arterial and venous blood lines can be connected. As shown in FIG. 5A, the drainage cassette 815 provides a common passageway to the drainage line 31 for both the arterial and venous blood lines during priming, cleaning and disinfecting operations. Water, dialysis solution or other fluids can be introduced into the blood passageway of the dialysis system 5 through the semipermeable membrane of the dialyzer 14 to flush air from the blood passageway and prime the blood passageway, or to clean and disinfect the blood passageway. The drainage cassette 815 can optionally include valves in either or both of the arterial or venous blood passageway. In one embodiment, an electronically controlled valve 831 in or near the modular drainage cassette 815 in the venous line can enable the blood pump of the blood pump cassette 13 to sequentially fill or empty the arterial line while the valve 831 in the venous line is closed, and then fill or empty the arterial line when the valve is open. In this manner, air or contaminants in the arterial line are forced to the drain outlet of the drain cassette 815 rather than into the venous tubing. Alternatively, the valve 831 can be positioned to control flow between the arterial line and the drain, for example, so that the contents of the venous line can be forced to the drain outlet rather than into the arterial line. The drain cassette 815 can also optionally include conductivity and / or temperature sensors 834, 835. A temperature sensor can be used to monitor the temperature of the fluid circulating through the blood line, for example, during thermal disinfection. A conductivity sensor can be used to monitor the conductivity of the water or dialysis solution circulating through the blood line, for example, during testing of the urea or sodium clearance of the dialyzer. The electronically controlled drain control valve 207 can be positioned at the drain outlet of the drain cassette 815 or can be positioned external to the drain cassette 815 (as shown in FIG. 5A). The drain control valve 207 can be useful, for example, when heated water or chemical disinfectants are circulating through the blood circuit components of the dialysis unit 51.The drainage cassette 815 can be configured to facilitate connection and disconnection to and from the front panel 511 or 811 of the dialysis unit 51. A single handle operated latch (e.g., a bayonet connection, etc.) can be included that secures the drainage cassette 815 to the front panel by turning a handle.

[0131] FIG. 21A also shows another embodiment of the blood pump cassette and organization tray assembly. In some embodiments, the organization tray 822 can be incorporated into the pneumatic actuation plate (or back plate) of the blood pump cassette 824. FIG. 21B shows the front panel assembly 811 with the top and middle plate components of the blood pump cassette 824 removed for clarity. In this example, the organization tray 822 and the back plate 816 of the blood pump cassette 824 are joined into a single molded piece. In this example, the air trap 819 is supported by an extension of the organization tray 822 and is positioned vertically higher than the embodiment shown in FIGS. 19 and 29. Moving the air trap to a higher position relative to the closure 813 or air-in-line detector 823 can increase the ability of the blood pump to draw air bubbles present in the venous tubing into the air trap 819 during a backflow procedure. For example, the inlet of the air trap 819 can be supported by the organizing tray 822 at a location above the outlet of the air trap when the blood circuit assembly is loaded into the dialysis unit. Additionally or alternatively, the inlet and / or outlet of the air trap can be supported by the organizing tray at a location above the highest point of the flexible tubing that extends from the outlet of the air trap to the closure location. Such an arrangement can help drive air in the venous tubing into the air trap 819.

[0132] In another embodiment of the invention, a modular drainage cassette can be included that has the ability to monitor and drain fluid (such as water or dialysis solution) flowing through the blood circuit of the dialysis unit 51, which includes a blood pump, a dialyzer blood flow compartment, an air trap, and arterial and venous blood tubing. As shown in FIG. 5A, the arterial and venous blood tubing can be connected to a drain chamber / air trap 4703 that ultimately leads to a drain line 31 when not connected to a patient. This connection allows for the circulation of heated water, for example, for cleaning and disinfecting the blood circuit compartment, for determining dialyzer clearance characteristics, or for priming the blood circuit with dialysis solution. In one embodiment of the invention, the drainage cassette 815 can include the drain chamber / air trap 4703, a valve 831 in one or both of the arterial and venous blood lines, a check valve 836 in the drain line, and temperature and conductivity sensors 834, 835 in one modular component that can be easily connected to or disconnected from the front panel of the dialysis unit 51. 21A, in one embodiment, the arterial and venous blood lines can be connected to a drainage cassette 815 through connection points 814 on the front panel 811. The drainage cassette 815 can include a channel or chamber that combines the fluid flow from the venous and arterial blood lines to exit through a common outlet into the drainage line 31.

[0133] As mentioned above, the drainage cassette 815 may optionally include a valve 831 in the venous line (or or the arterial line, or in both lines). In a preferred embodiment, the valve 831 is a pneumatically operated membrane valve that is actuated under the control of an electronic controller by an electromechanical valve plumbed to a pneumatic source. The drainage cassette 815 may also optionally include conductivity and heat probes 834, 835 in fluid flow channels or chambers in the housing of the cassette 815. In a preferred embodiment, the drainage outlet port, pneumatic control port, and electrical connections for the conductivity and heat sensors comprise paired connectors, one member of each pair rigidly attached to the housing of the drainage cassette 815 and the other member of each pair rigidly attached to the front panel 811 of the dialysis unit 51 to allow the user to quickly and easily load or unload the drainage cassette 815 from the front panel 811. The drainage cassette 815, like the other blood circuit components of the front panel 511 or 811 (including the dialyzer 14, blood pump cassette 13 or 824, air trap 19 or 819 and arterial and venous blood lines), can be configured to be easily detachable from the dialysis unit 51.

[0134] 31 illustrates an exemplary modular drainage cassette 815. In this view, a escutcheon 825 of the drainage cassette 815 includes markings that identify the arterial and venous line connection points 814. A handle 821 at the front of the escutcheon 825 can be grasped with one hand and turned to engage or disengage the drainage cassette 815 from the front panel 811. Blood line connectors 802 for each of the arterial and venous blood lines are shown engaged within their respective connection ports or connection points 814 of the drainage cassette 815.

[0135] FIG. 32 shows the drainage cassette 815 in an exploded view with a valance 825 in front of the front wall 826 of the drainage cassette 815. In this example, the front wall 826 seals and forms a front wall for a common channel or chamber 827 of the housing 828 of the drainage cassette 815. A common outlet 829 from the channel 827 to the drainage line is equipped with a fluid connector 830 mounted on the rear wall of the housing 828, which may optionally include a one-way check valve (e.g., a duckbill valve, etc.) to prevent fluid in the drainage line from re-entering the channel 827. The front panel 811 is equipped with a mating connector 830a, which is ultimately connected to a fluid line leading to the drain. The outlet 829 is preferably located higher than any of the fluid connection points 814a and 814b to trap and ultimately expel any air that may be present in the arterial or venous blood line when connected to the drainage cassette 815. In this regard, the fluid channel 827 may have a U-shape, with the venous and arterial blood line connectors 802 fluidly coupled with the respective connection ports 814a, 814b at the ends of the U-shape, and the drain outlet port 829 located at the bend of the U-shape. A valve 831 may be present in one or both fluid channel portions of the channel 827 leading from the connection points 814a and 814b. Thus, the valve may controllably open or close fluid communication in the channel 827 between the connection port 814 and the drain outlet port 829. In embodiments where only one valve 831 is provided in the channel 827, flow between one connection port 814 and the drain outlet port 829 may be controlled by the valve, while fluid communication between the other connection port 814 and the drain outlet port 829 may be permanently open. In the illustrated example, a pneumatically actuated membrane valve 831 mounted at the rear of the housing 828 is positioned over the portion of the channel 827a leading to the venous blood line connection point 814a. A mating pneumatic connector 831a mounted on the front panel 811 supplies positive or negative air pressure to the valve 831 to operate the valve, the pneumatic lines extending from the air pressure distribution module to the front panel 811, or a manifold located in the rear portion of the dialysis unit 51.Both connectors 830 and 831 can be configured to form a radial sealing engagement (e.g., with an elastomeric O-ring) with mating connectors 830a and 831a of the front panel 811 to allow the drainage cassette 815 to be relatively easily plugged in or unplugged from the front panel 811. Similarly, an electrical connector 833 can be mounted on the rear wall of the housing 828 to make an electrical connection outside of the channel 827 with a temperature and / or conductivity probe disposed within the channel 827. The electrical connector 833 can be configured to form a keyed connection with a mating electrical connector 833a of the front panel 811 to facilitate engagement and disengagement of the connectors when the drainage cassette 815 is installed or removed from the front panel 811. In some embodiments, the connection of the outlet drainage port connector 830, the valve control port connector 831 and the electrical connector 833 to their respective connectors on the panel 511 can be performed essentially simultaneously and / or in a single operation, for example, by pushing the drainage cassette 815 into place on the panel 511.

[0136] 33 shows a perspective view of the drainage cassette front wall 826. In the drainage cassette front wall 826, electrical connections between probes 834 and 835 and connector 833 are shown. In this example, probe 834 comprises a thermistor and one of a pair of conductivity sensors that extends into channel 827 to detect both fluid temperature and conductivity. Probe 835 also extends into channel 827 as the second probe of the pair of conductivity sensors that extend into channel 827.

[0137] FIG. 34 shows the main housing 828 of the drainage cassette 815 with the front wall 826 removed for clarity. Thermal and / or conductivity probes 834 and 835 are shown to illustrate their positioning in portion 827b of the fluid flow channel 827 (each probe is sealingly mounted to the front wall 826 but has an elongated element that penetrates the front wall 826 to be present in any portion of the fluid channel 827). An electrical connector 833 is shown positioned in a region of the housing 828 that is outside of the channel 827. In one embodiment, a check valve, such as a duckbill valve 836, can be mounted within the drainage connector 830 (shown in FIG. 32).

[0138] 35 shows a rear perspective view of the drainage cassette 815. A male fluid connector 830 is configured to connect to a mating connector 830a on the front panel 811, which is connected to a drainage line. A male pneumatic connector 831 is configured to connect to a mating connector 831a on the front panel 811, which is connected to a pneumatic line. A male electrical connector 833 is configured to connect to a mating connector 833a on the front panel 811, which provides an electrical connection from the thermal and / or conductivity sensor in the housing 828 to the system controller at the rear portion of the dialysis unit 51. A latch member 837 connected to the handle 821 is configured to be inserted into a keyhole in the front panel 811 to engage and lock the drainage cassette 815 to the front panel 811.

[0139] FIG. 36 shows the front panel 811 with the drainage cassette 815 removed. The drainage cassette recess 838 is configured to receive the drainage cassette 815. The user need only align the drainage connector 830, pneumatic valve connector 831 and electrical connector 833 of the drainage cassette 815 with their mating connectors 830a, 831a and 833a of the front panel 811 and press the cassette 815 into place to make the necessary pneumatic and electrical connections. The latch member 837 of the handle 821 of the drainage cassette 815 is inserted into the keyhole 837a and the handle 821 can be rotated 1 / 4 or 1 / 2 turn to lock the drainage cassette 815 into the recess 838, resulting in the configuration of the front panel as shown in FIG.

[0140] The modular feature of the drainage cassette 815 advantageously allows a user to easily install and remove substantially all of the blood-bearing components of the dialysis system (except, in one embodiment, the distal portion of the drainage line 31). Thus, the dialysis unit 51 can be used by more than one individual by simply replacing the blood-bearing components (e.g., blood circuit assembly and drainage cassette), each set being assigned to each individual user. The dialyzer semipermeable membrane, the ultrafiltration filter for the incoming water or dialysate in the dialysate side circuit, and the microbiological barrier provided by the dialysate side disinfection procedure between each use of the dialysis unit 51 allow the dialysate side components to be reusable between different users. The presence of the modular drainage cassette 815 together with other modular blood circuit components allows the dialysis unit 51 to be used conveniently in a multi-user clinical setting as well as in a single-user home environment.

[0141] According to another aspect of the invention, the front panel 511 (or other suitable components) of the dialysis unit 51 can be configured to accommodate dialyzer units 14 of various sizes and / or shapes. Different dialyzers can be designated to provide different treatment conditions for different patients, and in one embodiment, even the same patient over time. Thus, the dialysis unit 51 is preferably configured to operate with a plurality of different types of dialyzers 14. Often, different dialyzers 14 have different dimensions, such as the overall diameter and / or length of the dialyzer unit. In the exemplary embodiment shown in FIG. 23, the front panel 511 includes a dialyzer mount having a pair of "keyhole" features 520 configured to engage respective dialysate quick connect fittings on the dialyzer 14. Each keyhole feature 520 includes an upper insert area 520a sized to receive a portion of the quick connect fitting and a lower flange portion 520b having a width smaller than the overall diameter of the quick connect fitting to engage a groove area of ​​the quick connect fitting. To aid in understanding these features, FIG. 24 shows a dialyzer 14 with quick connect fittings 14a that are attached to the dialysate inlet and outlet ports of the dialyzer 14 (the blood inlet and outlet ports are located at the top and bottom ends of the dialyzer 14 shown in FIG. 24). The quick connect fittings 14a shown are of a standard type, and many, but not all, dialyzers 14 have dialysate inlet / outlet ports that are configured to engage with standard quick connect fittings 14a. Each quick connect fitting 14a includes a sliding element 14b that is moved to the right relative to the base 14c (as shown in FIG. 24) to engage the fitting 14a with the dialysate port on the dialyzer 14. When the sliding element 14b moves to attach the fitting 14a to the dialyzer 14, the groove 14d is closed. However, once the fitting 14a is properly positioned on the inlet / outlet port of the dialyzer 14, the sliding element 14b is released and a spring (not shown) moves the sliding element to the left as shown in Figure 24, resetting the groove 14d to the state shown in Figure 24. Thus, when the quick connect fitting 14a is properly engaged with the dialyzer 14, the groove 14d will be present as shown in Figure 24.

[0142] To attach the dialyzer 14 to the keyhole mechanism 520, the quick connect couplings 14a are partially inserted into the upper insertion areas 520a of the upper and lower keyhole mechanisms, respectively, such that the grooves 14d of each quick connect coupling 14a are aligned with the flanges of the lower flange portion 520b of the keyhole mechanism 520. (Note that the upper insertion area 520 of the lower keyhole mechanism 520 can be longer than that shown in FIG. 23 to accommodate a wider range of dialyzer lengths.) Once the grooves 14d are aligned with the flanges, the dialyzer 14 can be lowered so that the quick connect couplings 14a are fully received in the lower flange portion 520b of the keyhole mechanism 520.

[0143] According to another aspect of the invention, one or both of the keyhole mechanisms 520 are adjustable so that the weight of the dialyzer 14 is shared by both lower flange portions 520b of the keyhole mechanism 520. For example, in this exemplary embodiment, the lower keyhole mechanism 520 has a portion of the lower flange portion 520b that is adjustable in vertical position relative to the upper keyhole mechanism 520. This portion of the lower flange portion 520b is thus adjustable in vertical position so that, with the upper quick connect coupling 14a supported by the flange portion 520b of the upper keyhole mechanism 520, the movable portion of the flange portion 520b of the lower keyhole mechanism can be moved, for example, upwards, so that the lower quick connect coupling 14a is also supported by the flange portion 520b. Thus, the weight of the dialyzer 14 can be shared by both keyhole mechanisms 520. The flange portions 520b can be adjustable in any suitable manner. In this embodiment, the flange portion 520b has a "U" shaped member 520c that is slidable longitudinally along the longitudinal flange and can be locked in place by tightening a set of thumbscrews. The "U" shaped member 520c can engage with the quick connect fitting 14a such that the "U" shaped member 520c supports (at least partially) the weight of the dialyzer 14.

[0144] In the above embodiment, the dialyzer 14 is supported by a keyhole feature in the front panel 511, but the support structure for the dialyzer can be configured in other ways. For example, the upper insertion area 520a is not necessarily required. Alternatively, only a flange portion (e.g., in the form of a "U" shaped flange with opposing flange portions) can be provided to engage the dialyzer quick connect fitting. The flange portion can be offset from the front surface of the front panel 511 to provide clearance for the fitting and engage with a groove in the quick connect fitting. Furthermore, the flange portion does not have to be vertical as shown, but can be angled from the vertical, for example oriented horizontally. The flange portion can have a detent, catch, or other feature that helps hold the dialyzer in place.

[0145] According to another aspect of the invention, a bicarbonate, acid and / or other reagent supply may be selectively associated with the dialysis unit. As discussed above, the dialysis unit 51 requires a supply of certain chemicals to generate dialysate and / or other materials necessary for system operation. FIG. 25 illustrates a reagent supply 49 that may be used to supply acid, bicarbonate and / or other materials to the dialysis unit 52 (FIG. 21 illustrates the reagent supply 49 attached to the acid / bicarbonate connection point 512 on the front panel 511). The reagent supply 49 in this illustrative embodiment includes an E-shaped connector 491 configured to mate with the acid / bicarbonate connection point 512. As with other connections made by the user on the front panel 511, such as the blood line connection at connection point 514, the mating connector may be color coded or otherwise marked to ensure proper connection. For example, E-fork connector 491 and acid / bicarbonate junction 512 may be colored orange, arterial line 203 and its mating connection at junction 514 may be colored red, and venous line 204 and its mating connection at junction 514 may be colored blue. Extending from E-fork connector 491 are bicarbonate supply line 492, water supply line 493, and acid supply line 494 (see FIG. 6 and associated description of the function of these lines). Water supply line 493 provides water to bicarbonate source 28 (in this embodiment, a 750 g Altracart Bicarbonate cartridge (#500750A) sold by Baxter International Inc., containing powdered bicarbonate material, but may be any suitable source). Bicarbonate source 28 provides bicarbonate to dialysis unit 51 via bicarbonate supply line 492. In this embodiment, the acid supply line 494 leads to an acid bag spike 495 that can be used to pierce an IV bag or other container and withdraw a suitable acid therefrom. In this embodiment, the acid bag spike 495 includes a spike member 495a and a pair of spring clips 495b.The spring clips 495b are joined together at the center by a connecting bar such that the spring clips 495b and their connecting bar form an "H" shape such that the spring clips 495b can rotate relative to one another when the proximal ends of the spring clips 495b are clamped together. The spring clips 495b are configured to engage a connector element on an acid bag (or other acid source, not shown) so that the spike members 495a can remain engaged with the bag until the user removes the clips 495b. For example, the distal end of the clips 495b can include barbs that engage with the acid source, and the clip can be detached from the acid source by clamping the proximal ends of the clips 495b together and separating the barbing elements at the distal end of the clips 495b from the acid source. The acid bag spike 495 can also include a valve 495c (in this case a pinch clamp) that opens / closes the line of the acid bag spike 495. According to one aspect of the invention, the acid bag spike 495 can be replaced (by disconnecting it from the acid supply line 494 at the cap connector 496) with another component, such as an acid jug straw (not shown) or other structure. When used with a jug straw, the cap connector 496 can engage the opening of the acid jug to cover it like a cap. Alternatively, the jug straw can terminate in a spike, capable of penetrating a self-sealing (e.g. rubber) membrane that covers the opening of the acid jug. Thus, different types of components can be attached to the acid supply line 494, depending on the acid supply structure (jug, bottle, bag, etc.).

[0146] FIG. 26 is a close-up view of the E-shaped fork connector 491 and a corresponding connection point 512 on the front panel 511. The E-shaped fork connector 491 has three parallel prongs (corresponding to the bicarbonate and acid supply lines 492, 494, and the water supply line 493) that engage with corresponding receiving holes in the connection point 512. The E-shaped fork connector 491 and the receiving holes in the connection point 512 are configured such that the central lumen (the water supply line 493) is positioned above or otherwise out of the common plane of the two outer lumens (the bicarbonate and acid supply lines 492, 494). In this manner, the E-shaped fork connector 491 cannot engage with the connection point 512 unless it is properly oriented, thereby ensuring that the bicarbonate and acid supply lines 492, 494 are properly connected. The E-shaped fork connector 491 includes, for example, a pair of spring tabs 491a that can engage with corresponding slots 512a in the connection point 512 when the prongs are properly positioned in the receiving holes in the connection point 512. With tabs 491a engaged with slots 512a, E-fork connector 491 cannot easily come off connection point 512, helping to reduce the chance of accidental separation. E-fork connector 491 can be disconnected by pushing tabs 491a towards each other such that the barbs at the distal ends of tabs 491a separate from slots 512a. Connection point 512 has a similar spring tab 512b that can connect and disconnect connection point 512 to and from front panel 511.

[0147] In accordance with another aspect of the invention, a disinfectant connector (not shown) engages connection point 512 for use during a disinfection procedure. The disinfectant connector has three parallel prongs oriented similarly to E-prong connector 491 so that the prongs can engage receiving holes in connection point 512. Passages in the prongs of the disinfectant connector terminate in a common chamber within the disinfectant connector. Thus, during a disinfection procedure, the bicarbonate flow line, the acid flow line, and the water flow line are all interconnected, allowing each flow line to be disinfected during a disinfection procedure (this is shown as the dotted inverted "T" line at 49 in FIG. 6).

[0148] According to another aspect of the invention, blood lines 203, 204 are provided with connectors capable of making two types of connections. The first type of connection is a plug-in or press-fit type connection where the connector is pressed into the receiving lumen and a leak-free connection that is made without the need to rotate the connector or the receiving lumen. The second type of connection is a threaded connection where the leak-free connection is made by threaded engagement of the connector with a complementary element. For example, FIGS. 27 and 28 are perspective and side views of a blood line connector 202 for use with blood lines 203, 204 and engageable with blood line connection point 514 on front panel 511. Connector 202 includes a tube connection end 202a that connects to a corresponding blood line 203, 204 and a patient access connection end 202b that is configured to connect to both the patient access and connection point 514 to establish a leak-free connection. At patient access connection end 202b, connector 202 includes a frusto-conical member 202c having a female thread that is configured to engage with a male threaded patient access. For example, the frustoconical member 202c may be part of a male luer connector with a central tube 202 extending from the center of the frustoconical member 202c. When making a luer connection, the tube 202e extends into a female luer connector at the patient access, and the internal threads of the frustoconical member 202c may engage with the threads of the female luer connector at the patient access (arterial or venous). Such luer connections are standard when connecting blood lines to patient accesses. However, the connector 202 may be engaged with the connection point 514 by simply pushing the patient access connection end 202b into a receiving hole in the connection point 514. When making this connection, the exterior of the frustoconical member 202c may engage with a suitable seat or other surface or element (e.g., valve seat, O-ring, or other) within the connection point 514 to form a seal between the frustoconical member 202c and the connection point 514. Additionally or alternatively, central tube 202e can be used to engage connection point 514 to establish a suitable seal.A locking arm 202d extending rearwardly from the frustoconical member 202c can engage a hole 514a in the connection point 514 (e.g., a barb on the arm 202d can engage the hole 514a) to help hold the connector 202 in the receiving hole of the connection point 514. The connector 202 can be released by squeezing the arms 202d together (e.g., by pressing finger recesses on the distal ends of the arms 202d) to disengage the barbs from the holes 514a and withdraw the connector 202. Note that the connection point 514 includes a spring tab 514b that can selectively engage / disengage the connection point 514 with the front panel 511. The connector 202 can be made in any suitable manner, such as, for example, plastic molding as a single, integral part.

[0149] FIG. 29 shows a perspective view of another embodiment of the blood circuit assembly 17. This embodiment differs from that shown in FIGS. 18 and 19 in several respects. For example, in this embodiment, the blood lines 203 and 204 have a cross section similar in shape to a "figure 8", with one portion of the "figure 8" containing a lumen carrying blood or other fluids, and another portion of the "figure 8" carrying conductors. That is, the blood lines 203 and 204 have a lumen through which blood and other fluids can flow and another lumen through which conductors can pass. Further details regarding this and other arrangements are provided below with reference to FIGS. 37-49. As will also be described in more detail below, the conductors can be used to detect disconnection of the blood lines 203, 204 from the patient or other connection points. Additionally, the organization tray 171 of FIG. 29 differs from that shown in FIG. 19 in the following respects: That is, although the engagement member 174 can have slots or holes into which the blood lines 203, 204 engage, in this embodiment the engagement member 174 does not need to engage the blood lines 203, 204 to resist pulling the lines 203, 204 downward, for example, to load the lines into the closure. Alternatively, in this embodiment the blood lines 203, 204 can move freely relative to the engagement member 174. Another modification of the embodiment is that the engagement member 174 includes a push plate that spans both lines 203, 204. This is in contrast to the configuration of FIG. 19 where each line 203, 204 is engaged by an engagement member 174 that is independent of the other. The configuration of FIG. 29 can provide an advantage in some embodiments where a user can engage the lines 203, 204 with the slots 517 leading to the closure in a single operation (see FIG. 22). In one embodiment, the slots 517 may each be associated with an air detector that operates to detect whether or not there is an air bubble in the line 203 or 204 (e.g., by optical or other detection methods such that air in the line 203 or 204 may be detected by a respective air detector in one of the slots 517).Thus, the engagement member 174 can function to associate the lines with an air detector or other function in addition to or as an alternative to a closure or other mechanism to position the lines 203, 204 in a desired manner. In this embodiment, the engagement mechanism 174 includes a slot located on the underside of the push plate that engages with a narrower portion of the lines 203, 204 (e.g., the portion carrying the conductor) to position the conductor near the push plate. This can help position the lines 203, 204 within the slot 517 so that the conductor does not interfere with the air detector that operates to detect air in the lines 203, 204. As discussed above, the push plate slot that engages the lines 203, 204 can engage the lines so that they do not rotate relative to the push plate but can advance along their length relative to the push plate. FIG. 30 shows a close-up view of a portion of the blood circuit assembly of FIG. 29, illustrating an arrangement for at least partially conforming a portion of the organization tray 171 to the shape of the blood lines 203, 204 held by the tray 171. Similar to the engagement member 174, the portion of the tray 171 that engages the lines 203, 204 can be configured to orient the lines 203, 204 so that the conductor portions of the lines face outward. This can help to properly position the lines 203, 204 relative to the engagement member 174 or other portions of the assembly 17.

[0150] It should be understood that any and all of the aspects of the invention described herein may be combined or otherwise integrated with any of the other aspects of the invention and / or embodiments described. For example, a dialysis system incorporating one or more aspects of the invention described herein may have a line disconnection feature such as that described in connection with Figs. 37-49. Such a disconnection feature may have features such as 1) an electrical circuit or other suitable circuit that detects a change in voltage, resistance or other property indicative of a disconnection of the blood line 203, 204 with respect to the associated connector, 2) positioning of the detection electrode in suitable proximity to the patient or other reference, 3) one or more connector arrangements, 4) a blood line tubing configuration or other suitable configuration in which the blood line supports both a fluid flow lumen and an electrically conductive function. For example, in one aspect of the invention, a blood circuit assembly may include electrical circuitry suitable for use in detecting disconnection / connection of the blood line, one or more blood pumps, an air trap, and one or more blood lines in the organization tray. Such a configuration allows a user to easily make several different connections, whether fluidic, pneumatic and / or electrical, with relatively little complexity.

[0151] Thus, aspects of the present invention generally relate to systems and methods for detecting disconnection of indwelling vascular lines or attached tubing, such as catheters or needles, used in dialysis treatments. Disconnection, if not detected promptly, can lead to rapid exsanguination, especially if the blood in the catheter or tubing is under positive pressure. Examples of environments with positive intravascular pressure include positive pressure associated with arteries or arteriovenous fistulas, or positive pressure associated with extracorporeal blood pump circuits. In hemodialysis, for example, blood pumps can generate blood flows of 400 ml / min to 500 ml / min, making rapid, reliable disconnection detection particularly desirable. Indeed, any medical treatment involving a relatively high flow or high pressure extracorporeal circuit (such as, for example, hemoperfusion or cardiopulmonary bypass) can be made safer by having an effective system for monitoring the integrity of the arteries (withdraw) and veins (return).

[0152] In hemodialysis, for example, extracorporeal blood circulation can be achieved by vascular access using either a single indwelling catheter or two separate indwelling catheters. In a single catheter system, blood is alternately withdrawn from and returned to the body through the same cannula. Disconnection in this system can be quickly detected by placing an air monitor in the line at or near the pump inlet, since air will be drawn into the line from the cut site during the blood withdrawal phase of pumping. On the other hand, in a two-catheter system, blood is usually withdrawn from the body sequentially through one catheter inserted into a blood vessel or fistula, and returned to the body through a second catheter inserted some distance from the first catheter in the same vessel, or into a completely separate vessel. In a two-catheter system, a sensor can also be used to monitor for catheter or tubing dislodgment in the blood withdrawal or "arterial" segment by detecting the presence of air trapped in the arterial tubing as blood is withdrawn from the vessel under negative pump pressure and / or positive fistula pressure. However, air-in-line detection cannot reliably detect disconnection of the venous (return) segment of the extracorporeal circuit, where air would not be introduced into the line if the blood withdrawal path was intact. Thus, being able to detect interruptions in the continuity of the return line from the extracorporeal pump to the vascular access site is particularly important.

[0153] In one aspect, the invention includes a system for detecting whether a vascular access device, such as a needle, cannula, catheter, etc., has been disconnected or detached from a blood vessel or vascular graft. The system includes a fluid delivery device that provides a flow of fluid through a tube or conduit into the blood vessel through an indwelling needle or catheter at a first site of the blood vessel or graft. The fluid can be an electrolyte or other solution suitable for intravenous infusion, or can be blood or blood components. An electrode is disposed in contact with or in fluid communication with a lumen of the conduit, and a second electrode is disposed in fluid communication with blood in the blood vessel or graft through a second of the blood vessel or graft. An electronic circuit is connected to the first and second electrodes and configured to send control signals to the first and second electrodes to measure electrical resistance of the fluid between the first and second electrodes, where at least one of the electrodes is disposed closer to the blood vessel or graft than the fluid delivery device. In some embodiments, the electrodes are disposed about 50%-70% of the distance from the fluid delivery device to the blood vessel or graft. In other embodiments, the electrode is positioned about 70%-90% or more of the distance from the fluid delivery device to the blood vessel or graft. The fluid delivery device can include a pump for blood or other therapeutic or diagnostic fluids. The fluid delivery device can be part of a hemodialysis blood flow circuit that may or may not include a blood pump, a dialyzer cartridge or an air trap and associated tubing. The second electrode can be positioned in contact with the lumen of a second conduit or tube in fluid communication with the blood vessel or graft at the second site. The second conduit can form part of the fluid flow path from the blood vessel or graft to the fluid delivery device. The fluid in the second conduit can be blood being pumped to an extracorporeal blood flow circuit.

[0154] The system can include first and second connectors connecting a pair of vascular access catheters that access vessel or vascular graft segments at two different locations. The first and second connectors can each be connected to a flexible tube that leads to a fluid delivery device. Each connector can include an electrode exposed in a lumen of the connector. Each connector can have a wire attached thereto, the wire being connectable to electronic circuitry at its other end. The flexible tube can be a dual lumen tube having a first lumen for carrying fluid and a second lumen for carrying wires. The wires of each tube can be connected to a connector for connection to electronic circuitry at the other end of the tube.

[0155] The electronic circuit or associated microprocessor can be configured to convert a voltage measured by the electronic circuit across the terminals connected to the electrodes into a resistance value. The system can include a controller configured to receive a signal from the electronic circuit or microprocessor, the signal representing the electrical resistance between the electrodes, and the controller is programmed to trigger an alarm signal when the electrical resistance value exceeds a predetermined threshold. The alarm signal can be an audible or visual signal to the person whose vessel is being accessed, and optionally the alarm signal can include an electrical command to the tubing closure device. The tubing closure device can be actuated to mechanically close one or more of the tubes leading from the vascular access site. The tubing closure can be operated in a number of ways, such as electromechanically, hydraulically, or pneumatically.

[0156] In another aspect, the invention includes an apparatus for monitoring continuity between a vascular access device and a vessel or vascular graft segment, comprising first and second vascular connectors, the first connector attached at a proximal end to a distal end of a fluid carrying lumen of a first dual lumen tube and the second connector attached at a proximal end to a distal end of a fluid carrying lumen of a second dual lumen tube. The first connector comprises a first electrode in contact with the lumen of the first connector and electrically connected to a wire in the wire carrying lumen of the first dual lumen tube, and the second connector comprises a second electrode in contact with the lumen of the second connector and electrically connected to a wire in the wire carrying lumen of the second dual lumen tube. The wires in the first dual lumen tube and the wires in the second dual lumen tube are each connected to an electrical connector at the proximal end of the dual lumen tube. The distal end of each connector can be configured with a locking feature that provides a reversible airtight connection between the connector and a mating connector of a vascular catheter. The proximal end of the dual lumen tubing can be connected to a blood pump on the arterial side and an air trap on the venous side, and in a hemodialysis system, the blood pump and the air trap can each be reversibly connectable to a dialyzer cartridge.

[0157] In another aspect, the invention comprises a vascular connector comprising a proximal fluid connection end, a distal fluid connection end, and an electrode configured to electrically connect a fluid carrying lumen of the connector to a wire external to the vascular connector. The proximal end of the connector can be configured to connect with a flexible tube and the distal end of the connector can be configured to connect with a mating connector of a vascular catheter. The electrode can be located in a conduit of the connector connecting the lumen of the connector to the exterior of the connector. The electrode can be contained within the conduit to provide an airtight seal between the lumen and the exterior of the connector. An elastomeric member, such as an O-ring, can be located between the electrode and the conduit to contribute to the airtight seal.

[0158] In another aspect, the invention provides an electrical circuit for measuring the resistance of a liquid between a first electrode and a second electrode, the first electrode being connected to a first terminal of the electrical circuit and the second electrode being connected to a second terminal of the electrical circuit, the circuit comprising: a capacitor C1 connected at a first end to the first terminal and a capacitor C2 connected at a first end to the second terminal; a known reference resistor Rref connected at its first end to the second end of the capacitor C1; (a) a first reference voltage V+ connected to the second end of Rref and a second lower reference voltage V− connected to the second end of C2; to form a first switch configuration, or (b) a first reference voltage V+ to the second end of C2 and a lower second reference voltage V- to the second end of Rref to form a second switch configuration, and a measuring means for measuring a voltage Vsense at the connection between C1 and Rref, whereby the electrical circuit is configured to determine a value of the resistance of the liquid based on the known reference voltage Rref and the observed voltage Vsense for each of the first and second switch configurations. The resistance Rref can be selected to be a value that allows for conductivity measurement of an electrolyte or other solution suitable for intravenous infusion. The electrolyte can include a dialysate. The resistance Rref can also be selected to allow for measurement of the resistance of a volume of blood between the first and second electrodes. Conductivity Circuit The exemplary electrical circuit shown in FIG. 37 can be used to measure the conductivity or resistance of a fluid of interest. In one embodiment, the fluid can be an electrolyte or dialysis fluid, and the circuit can ultimately provide a measurement of the fluid's conductivity to ensure its suitability for intravascular administration. In addition to monitoring the concentration of dissolved solutes in the fluid, the electrical circuit can also monitor for possible interruptions in the continuity of the fluid between the electrodes connected to the circuit. For example, it can be used to monitor an intravenous fluid line for the presence of air bubbles, or the presence of contaminants. In another embodiment, the fluid can be blood, and changes in the measured electrical resistance of the blood flow path (e.g., in a conduit) can be used to indicate whether a discontinuity occurs between the blood flow path and the measurement electrodes. For example, the blood flow path may include a column of blood between two electrodes, including an indwelling needle or catheter in a segment of a blood vessel, arteriovenous fistula, or graft. Disconnection of the vascular access can introduce air into the blood flow path, changing the resistance of the blood column between the electrodes. The electrical circuit can be easily modified (depending on the application) to adjust for the difference between the impedance of the blood flow path and the impedance of the dialysis fluid.

[0159] The circuit shown in FIG. 37 can be used to measure the unknown resistance Rx of the target medium 1 using low-cost electronic components, especially when the unknown resistance includes a conductive path through an electrolytic fluid. A switching network 2 with a pair of multiplexers allows connection of node VA to reference voltages V+ and V-. The target medium 1 with the unknown resistance Rx is connected to terminals VTA and VTB 3, forming a voltage divider with a reference resistor Rref 4. To perform a conductivity measurement, an AC voltage can be provided to the target medium 1 through the switching network 2 to the voltage divider created by the known reference resistor Rref 4 (e.g. 680 ohms for dialysis fluid) and the unknown resistance Rx of the target medium 1. The midpoint of the voltage divider is measured. The signal Vsense at point 8 is buffered by an amplifier 10 to generate the input signal Vin of an analog-to-digital converter (ADC) 111. Vsense switches between two values ​​as the voltage divider is driven first in one direction and then in the other direction. This signal is only valid for a short period of time after switching because the fluid in the conductivity cell 1 is AC coupled to the circuit through capacitors C1 and C2 6. Thus, DC blocking capacitors C1 and C2 6 can be used to prevent DC current from passing through unknown resistances (which may include a conductive path through the electrolytic fluid or blood). In one embodiment, the series capacitors C can each include two capacitors in parallel, one having a value of, for example, 0.1 μF and the other having a value of, for example, 10 μF. Series resistors 7 can be used to reduce exposure to noise and surge voltages due to the switch network and other sensing circuitry. The ADC 111 can take multiple samples of the signal as the circuit switches between the two configurations.

[0160] The switching network 2 can be driven by a pair of alternating binary control signals 131, 144 that connect VA to V+ and VB to V- during one half-cycle and VB to V+ and VA to V- during the other half-cycle. This results in a waveform at the Vsense node 58 similar to the waveform 20 shown in FIG. 38. In this embodiment, Vref is 4 volts, resulting in a Vsense amplitude of less than 4 volts as shown in FIG. 38. The voltage divider 8 provides voltages V+ and V- close to the positive reference voltage Vref and close to ground, respectively. In one embodiment, R1 can have a value of 10 ohms and R2 can have a value of 2K ohms. When both multiplexers of the switching network 2 are commanded to zero, the circuit is off and the lower voltage is applied to the terminals VTA and VTB 3. When VA is high and VB is low, the higher voltage is applied to the reference resistor Rref 4 and the lower voltage is applied to the target medium 1 with unknown resistance Rx. When VB is high and VA is low, the higher voltage is applied to the target medium 1 having an unknown resistance Rx and the lower voltage is applied to the reference resistor Rref 4.

[0161] The change in voltage ΔVsense before and after each square wave edge can be shown to depend only on the reference resistor Rref 4, the unknown resistance Rx of the target medium 1, and any series resistance (including, for example, Rs 7), and is generally independent of the series capacitances C1 or C2 6, because during this brief period the capacitors act as incremental short circuits. In particular, Δα=ΔVsense / (V+-V-)=(Ry-Rref-Rth) / (Ry+Rref+Rth)=(ρ-1) / (ρ+1) where Ry=Rx+2Rs+Rth, Rth=source series resistance from multiplexer 2 and voltage divider 8, and ρ=Ry / (Rref+Rth). (The source series resistance Rth can be derived as the sum of the resistance of multiplexer 2 and the Thevenin equivalent resistance of voltage divider 8. For example, if R1=10 ohms, R2=2K ohms, then Rth=R1∥(R1+R2)=9.95 ohms.) Thus, if Ry is a short circuit, ρ=0 and Δα=-1. Then the change in voltage at the sense node ΔVsense is equal to the voltage change at VB, which has the opposite amplitude as the drive node at VA. If Ry is an open circuit, ρ=∞ and Δα=1. Then the change in voltage at the sense node ΔVsense is equal to the voltage change at the drive node VA. Thus, if this change in voltage is measured, the previous equation can be solved for the unknown resistance Rx.

[0162] Rx=ρ(Rref+Rth)-2Rs-Rth, where ρ=(1+Δα) / (1-Δa) As shown in Figure 37, a low pass filter 9 can be formed by resistor Rf and capacitor Cf to remove high frequency noise. In one exemplary configuration, Rf can have a value of 1K ohms and Cf can have a value of 0.001 μF. A buffer amplifier 10 and an analog-to-digital converter (ADC) 111 can then measure the sensed voltage to a computer or digital signal processor (not shown).

[0163] The reference voltages V+ and V- can be advantageously derived from a voltage divider 8 such that V+ is close to the ADC111 reference voltage Vref and V- is close to the ADC111 ground reference voltage. For example, if R1=10 ohms, R2=2k ohms and Vref=4.0V then V+=3.980V and V-=0.020V. This places both voltages within the active sensing region of the ADC111 but close to its edge, allowing them to be used for calibration (described below). A switch SW1 12 can be used to aid in the calibration of the load resistance sensing.

[0164] Several improvements can reduce errors associated with component value variations. First, a calibration step can be introduced in which VA is switched to V+ for a relatively long period of time until it settles and is approximately equal to V+, at which point ADC111 can make another measurement of Vsense. A second calibration step can include switching VA to V- for a relatively long period of time until Vsense settles and is approximately equal to V-, at which point ADC111 can make another measurement of Vsense. This allows ADC111 to measure both V+ and V-.

[0165] Second, as shown in FIG. 38, while the square wave switches, the ADC 111 readings before and after both edges of the switching waveform can be used to calculate the dimensionless number Δα as follows: Δα=ΔVsense / (V+-V-)=[(V2-V1)+(V3-V4)] / 2(V+-V-) As a result, both edges of the waveform can be used to measure ΔVsense=[(V2-V1)+(V3-V4)] / 2, which may cancel out the asymmetric response to the circuit. Alternatively, the average voltage at approximately the midpoint of the waveform can be used, so that, for example, Δα=ΔVsense / (V+-V-)=[(V7-V6)+(V7-V8)] / 2(V+-V-) and ΔVsense=[(V7-V6)+(V7-V8)] / 2. Furthermore, only the differential measurement of the input signal Vin of the ADC 111 can be used. Thus, any offset error of the buffer amplifier 10 and the ADC 111 can be cancelled. Also, Δα is a ratiometric quantity based on measurements using the same signal path. Thus, any gain error of the ADC 111 can be cancelled.

[0166] The reference resistor Rref 4 can be arbitrarily chosen to be equal to the geometric mean of the endpoints of the unknown resistance of the desired range, taking into account the series resistance Rs 7. For example, if Rs=100 ohms and Rx varies from 100 ohms to 3000 ohms, then Ry=Rx+2R varies from 300 ohms to 3200 ohms, and Rref should be approximately the square root of (300 ohms 3200 ohms)=980 ohms. To measure an unknown resistance in the range of 100k ohms to 300k ohms (such as in a column of blood extending from one electrode to another through an arteriovenous fistula), the reference resistor Rref 4 can be changed to approximately 200k ohms and the filter capacitor Rf of the low pass filter 9 at the input to the buffer amplifier 10 can be completely removed.

[0167] Because the output of the voltage divider is a nonlinear function of its resistor ratio, errors or noise in the readings from the ADC 111 will result in their lowest fractional error (sensitivity) in the resulting calculation of Ry when Ry is equal to Rref, and the more sensitivity increases the more Ry diverges from the reference resistor Rref. Specifically, it can be shown that the sensitivity in resistor ratio is:

[0168] Sρ=(1 / ρ)·∂ρ / ∂Δα=2 / [(1+Δα)(1-Δα)]=2 / [1-(Δα) 2 ] When Ry=Rref, ρ=1, Δα=0 and Sρ=2. Thus, for a change in Δα of 0.001 (0.1% of ADC full scale) about this point, the calculated resistance Ry changes by 0.002 or 0.2%. As ρ diverges from 1, the sensitivity increases, as shown in Table 1.

[0169] [Table 1]

[0170] Figure 39 shows that the noise / error sensitivity doubles for an unknown / reference resistance ratio of approximately 6:1, and triples for a ratio of 10:1. Resistance measurements outside this range may suffer from increased sensitivity to noise and errors.

[0171] For calibration purposes, switch SW1 12 can be used to take a resistance measurement to calibrate out the point where Rx=0. Preferably, this switch 12 should be placed across terminals VTA and VTB 3 or as close as possible to them, thereby providing a true zero point calibration. However, in practice, placing switch 12 close to terminals VTA and VTB 3 may make switch 12 susceptible to external noise and surge voltages and may introduce DC leakage currents into target medium 1.

[0172] The use of series capacitances C1 and C2 6 and square wave is important for the unknown resistances that include the electrolyte conductive path. There are at least two reasons for this. First, in many applications it may be important to prevent direct current from flowing through electrolytes or body fluids with similar properties, which may otherwise cause electroplating and / or electrolysis of the electrodes at terminals VTA and VTB 3. In this circuit, capacitors C1 and C2 6 block direct current. Furthermore, because capacitors can pass very small currents (microamps or less), using an alternating square wave voltage can help to further limit the average current.

[0173] Second, if a small electrochemical DC voltage is induced in the target medium 1 (e.g., electrodes in the fluid paths may oxidize at different rates over time), this DC voltage can be blocked by capacitors C1 and C2 6. Through the process of calculating the unknown resistance Rx of the target medium 1, any residual DC voltage can be cancelled out, because the method for calculating the resistance makes a differential measurement.

[0174] Blood vessel cut detector By appropriately modifying a conductivity measurement circuit such as the one described above, it is possible to detect the conductivity of blood and changes in conductivity. More specifically, it is possible to detect the changes that occur in the conductivity of a volume of blood when air enters that volume. This situation can occur, for example, if an intravascular access site becomes dislodged in an extracorporeal blood circuit.

[0175] The circuit shown in Figure 37 can be used to measure the resistance of a volume of fluid in the conductivity cell or line 1. When measuring Rx of the conductivity cell 1, which represents the resistance or conductivity of a volume of dialysis solution, a convenient value for the reference resistor Rref 4 can be selected to be approximately 680 ohms. When measuring Rx of line 1, which represents the resistance or conductivity of a column of blood extending from a first cannula or needle through an arteriovenous fistula to a second cannula or needle, a convenient value for the reference resistor Rref 4 can be selected to be approximately 200 kOhms.

[0176] Advantages of using this circuit to monitor the continuity of a column of bodily fluid such as blood or plasma include: capacitive coupling to the conductivity cell or line 1 blocks direct current that could plate and corrode the electrodes at terminals VTA and VTB, and for patient safety, voltage and current levels are very low and disconnected, and current flows only for short periods while a measurement is being taken. No current flows between measurements.

[0177] With a lower value of reference resistor Rref 4 (e.g. 680 ohms), the circuit is properly configured for dialysate conductivity measurements. With a much higher value of reference resistor Rref 4 (e.g. 200 kohms), the circuit is properly configured for measuring the resistance between the arterial and venous needles to detect dislodging of the vascular needle from the arteriovenous fistula.

[0178] Electrode arrangement The continuity of the fluid column leading from the fluid delivery device to the patient's blood vessel or vascular graft can be monitored using the electronic circuitry described above. The fluid being delivered can include blood or any electrolyte, including dialysis fluid. Although the following discussion involves a hemodialysis system, the same principles of operation of the present invention can be applied to any device configured to deliver fluid to a patient through a vascular access. In the embodiment shown in FIG. 40, the conductivity of a volume of blood or other fluid in the fluid flow circuit 100 of a vascular dialysis machine 200 can be monitored electronically using electrodes at each end of the volume that are in direct contact with the blood or other fluid. Using an electrical circuit such as that shown in FIG. 37, one electrode can be connected to the VTA terminal and the other electrode can be connected to the VTB terminal of the circuit. The voltage applied by the circuit to the electrodes can be a DC voltage that is small enough (e.g., about 4 volts or less), short enough, and sufficiently disconnected to prevent any damage to the patient. In this example, a fluid flow circuit 100 is shown that includes arterial access needle 102, arterial catheter tubing 104, arterial catheter tubing connector 106, arterial blood circuit tubing 108, transition 110 between vascular circuit tubing 108 and hemodialysis machine 200, blood pump inlet line 112, blood pump 13, blood pump outlet line 116, dialyzer 14, dialyzer outlet line 120, air trap 122, transition 124 between hemodialysis machine 200 and venous blood circuit tubing 126, venous catheter tubing connector 128, venous catheter tubing 130, venous access needle 132, and the intraluminal volume of the portion of the patient's blood vessel or fistula 134 located between arterial access needle 102 and venous access needle 132. The invention described herein also encompasses situations where the arterial access needle may be in one blood vessel of the patient and the venous access needle may be in a separate vessel some distance away from the arterial access site. Additionally, the circuitry described above can be used to monitor the integrity of the vascular access in a fluid delivery system that does not have a venous return line, as shown in FIG.In that case, for example, the electrode at position B can be paired with an electrode in contact with the fluid of a dead-end line that communicates with a second needle or cannula that accesses the blood vessel or vascular graft. In another example, an indwelling hollow cannula or solid trocar in the blood vessel segment can be equipped with a conductive wire that can thereby serve as the second electrode in the monitoring system. The blood vessel segment being accessed can be a surgically created arteriovenous fistula or can include an artificial conduit such as a GoreTex® vascular graft. The term "arterial" is used herein to refer to the portion of the blood flow circuit that directs blood away from the patient toward the hemodialysis machine 200. The term "venous" is used to refer to the portion of the blood flow circuit that directs blood away from the hemodialysis machine 200 back toward the patient. The term "access needle" is used to refer to a needle or catheter device that penetrates the patient's blood vessel segment or fistula. In various embodiments, it can be permanently fused or reversibly connected to the corresponding catheter tubing 104, 130.

[0179] The continuity of any segment of the fluid flow circuit 100 can be monitored by positioning two electrodes in fluid contact on either side of the fluid and blood containing segment of interest. One electrode can be placed in continuity with the lumen on the venous side of the blood flow circuit and a second electrode in continuity with the lumen on the arterial side of the blood flow circuit to monitor for disconnection of the arterial access needle 102 or arterial catheter tubing 104 or venous access needle 132 or venous catheter tubing 130. In one embodiment, two electrodes can be placed at or near the dialysis machine 200, with one electrode in contact with the blood upstream of the blood pump 110 and a second electrode in contact with the blood downstream of the dialyzer 14 and / or air trap 122. For example, electrodes can be incorporated at the transition locations 110 and 124.

[0180] In another embodiment, one of the electrodes can be positioned to contact the fluid in the fluid flow circuit 100 at a point closer to the vascular access site 134 than the equipment (e.g., dialysis machine) used to deliver the fluid flow to the accessed blood vessel or vascular graft. In a preferred embodiment, both electrodes can be positioned closer to the patient's blood vessel or vascular graft than the equipment associated with the dialysis machine 200. This can further reduce electrical interference associated with the dialysis machine 200. Electrode A can be conveniently located at or near the arterial catheter tubing connector 106, and the second electrode B can be conveniently located at or near the venous catheter tubing connector 128. In this configuration, the electrical conduction path from the first electrode through the patient's vascular access to the second electrode is much shorter, i.e., has lower electrical resistance, than the path extending back toward the dialysis machine 200. In one embodiment, the access catheters 104 and 130 can be as short as about one foot, and the arterial tubing 108 and venous tubing 126 can be about six feet long. Due to the conductive properties of the fluid in the circuit, the electrical resistance associated with the pathway incorporating the tubing 108 and 126 and components of the dialysis machine 200 can be many times greater than the electrical resistance associated with the pathway through the patient's blood vessels or fistula 134.

[0181] Thus, electrical interference associated with the dialysis machine 200 is reduced and changes in electrical resistance due to access-related disconnections can be more easily detected. Preferably, electrodes A and B are positioned greater than 50% of the distance from the dialysis machine to the patient. More preferably (more conveniently), electrodes A and B are located near the last severable fluid connection before reaching the patient. In one embodiment of the hemodialysis system, blood tubing 108 and 126 are approximately 6 feet in length and arterial catheter tubing 104 and venous catheter tubing 130 are approximately 2 feet in length or less. A convenient location for electrodes A and B is then at the arterial line connector 106 and venous line connector 128 (which may be, for example, a Luer type connector or a variation thereof) that connects the arterial blood circuit tube 108 and venous blood circuit tube 126 to the arterial catheter tube 104 and venous catheter tube 130. Connector Electrodes As shown in FIG. 41A and FIG. 41B, in one embodiment, a blood line connector for a blood circuit of a hemodialysis system can incorporate an electrode that can contact liquid within the lumen of the connector. In one aspect, the electrode can comprise an annular conductive cap 310 disposed at the tubing connection or proximal end 302 of any suitable connector, such as, for example, connector 300. The electrode is preferably constructed from a durable and corrosion-resistant material, such as, for example, stainless steel. The distal coupling end 304 of connector 300 can be configured for sealing engagement with a corresponding luer-type connector, for example, of an arterial or venous catheter. The inner annular surface 312 of cap 310 (partially or in whole) can contact liquid present within lumen 314 of the connector. As shown in FIG. 41B, an O-ring 316 or suitable sealant can be disposed between cap electrode 310 and proximal end 302 of connector to maintain a fluid-tight connection between the connector and any flexible tubing attached to the connector.

[0182] Elastomeric O-rings may be particularly useful in hemodialysis systems, or other extracorporeal systems where blood-bearing components are disinfected or sterilized using heated fluids. The thermal expansion rate of the plastic components of the connector may be significantly different than the incorporated metal electrodes, so that a permanent seal may not be maintained after one or more sterilization or disinfection procedures. By adding an elastomeric component, such as an O-ring, to the joint between the electrode and the connector seat in which the electrode is located, a seal can be maintained by accommodating the different expansion and contraction rates between the electrode and the connector.

[0183] As shown in FIG. 42, in one embodiment, a conductive electrode 310 (e.g., constructed from stainless steel) can be incorporated into a portion of the connector 300 (either at its proximal end 302 or at its distal connection end 304) onto which an end of a flexible tube 318 can be disposed. In this embodiment, the electrode 310 is generally cylindrical and has a tapered portion 320 at the proximal end to allow for easier slip-fit ​​attachment of the end of the segment of the flexible tube 318 to the outer surface of the electrode 310. As shown in FIG. 42, the inner surface of the electrode 310 has an internal ledge 322 that allows the electrode cap 310 to slide over and abut the proximal end 302 of the connector 300. The connector 300 can be constructed from any suitable rigid material, including metal or, more typically, a plastic material. The ledge 322 helps ensure that the smaller diameter inner surface 312 of the electrode 310 is properly positioned to contact fluid (e.g., blood) passing through the lumen 314 of the connector 300. The connections between the connector 300 and the electrode 310 and between the electrode 310 and the terminal end of the overlying flexible tubing 318 can be made airtight or permanent using any suitable adhesive compatible with the composition of the components.

[0184] To ensure a more secure seal to prevent blood leakage between the connector and the electrode, and to limit the area under the electrode where blood components may migrate and become lodged, an O-ring 316 may be incorporated on the inner surface of the electrode 310 near the electrode inner ledge 320. This is shown in expanded detail in FIG. 42. In this example, the O-ring 316 seals between the stainless steel electrode 310 and the distal end 302 of the connector 300. To hold the extended end of the flexible tube 318 over the proximal end 302 of the connector 300, the connector design may incorporate a piercing element 324 on the proximal end 302 of the connector 300. In one embodiment, the electrode 310 is held in place by a portion of the flexible tube that extends over both the electrode 310 and the piercing 324 of the connector 300.

[0185] A wire 326 may be soldered, welded, or otherwise secured to the outer surface of the electrode 310, and may run under the overlying extension tubing 318 until it exits more distally along the connector 300. The wire may thus conduct electrical signals to and from the electrode 310 when the inner surface 312 contacts the intraluminal fluid (e.g., blood). In the illustrated example, the wire 326 is soldered to the distal portion of the electrode 310 and runs under the tubing 318 to emerge at the abutment of the tubing 318 with a corresponding stopper 326 on the connector 300.

[0186] In another embodiment as shown in Figures 43A-43C, a connector 400 as described in US Patent Publication No. 2010 / 0056975, the contents of which are incorporated herein by reference, is modified such that a central portion 406 of the connector 400 can incorporate electrodes. Locating the electrodes along the central portion 406 of the connector 400 eliminates the need to modify the distal coupling end 404 of the connector and eliminates any modification of the interaction between the termination of the flexible tubing and the proximal end 402 of the connector. In this example, the blood line connector 400 is configured to make two different types of sealed connections at its distal coupling end 404, including a female thread type connection 405 for a Luer type connector of a patient access line and an external press fit type connection 407 with a dialyzer port for recirculation of priming and disinfecting fluids through the blood-bearing components of the dialysis system. The press-fit feature 407 is formed with a frusto-conical shape on the outer surface of the distal end 404 of the connector 400, and the luer-fit thread-type feature 405 is formed on a corresponding inner surface of the distal end 404 of the connector 400. The outer surface of the frusto-conical member is configured to sealingly engage with a seat of a mating connector of the dialysis machine 200 or other device. A pair of locking arms 408 extend proximally from the distal coupling end 404 of the connector 400, each of which may have a barbed portion 409 that engages with a corresponding locking feature of the mating connector of the dialysis machine, and a finger recess 410 that aids in removing the barbed portion 409 from the dialysis machine. The barbed portion 409 serves to lock the frusto-conical member into sealing engagement with its mating connector of the dialysis machine when making a press-fit connection. The distal end of the locking arm may be configured to attach to the connector through a flange 411 located proximal to the frusto-conical portion 407 of the connector 400. The connector 400 has a proximal tubing attachment end 402 that sealingly engages a flexible tube. The tubing attachment end 402 can have one or more piercing features 412 that help prevent the end of the flexible tube from becoming dislodged from the connector 400.

[0187] 43B shows a side view of the connector 400 revealing an access feature or port 420 that can allow for placement of an electrode in direct communication with the lumen of the connector 400. In other embodiments, the access feature can house an elastomeric stopper (with or without a septum) to allow sampling of fluid from within the lumen 414 of the connector 400 using a syringe with a sharp or blunt needle. Or, the feature can serve as a port that allows connection of another fluid line to the lumen 414 of the connector 400.

[0188] In yet another embodiment, as shown in the cross-sectional view of FIG. 43C, the middle section 406 of the connector 400 can have two access ports. The fluid access port 420a can serve as a sampling port and the electrode port 420b can serve as an electrode cradle. An elastomeric stopper 422 in the sampling port 420a can be shaped to extend into the lumen 414 of the connector 400, allowing sampling of the fluid in the lumen 414 with a needle while simultaneously maintaining an airtight seal. Alternatively, a luer connector with a septum cap or seal can be incorporated into the port, which can connect with a syringe or catheter with a mating luer connector. The electrode port 420b can serve as a seat or cradle for the electrode 424. It can be pressed or cemented in place and sealed with adhesive or with an O-ring 416 as shown. The wire 426 can be soldered, welded, or otherwise secured to the outer surface of the electrode 424, and the wire 426 can be routed proximally toward the dialysis machine 200 through the arterial tubing 108 or venous tubing 126 to which the connector 400 is attached.

[0189] In any of the above electrode embodiments, the electrodes may be replaced with appropriately dimensioned thermistors, or a combination of thermistors and electrical conductors, for the additional purpose of measuring the temperature of the fluid passing through the connector 300, 400 or a variation thereof. Wire Assembly In one embodiment, the wires carrying the electrical signals to or from a pair of electrodes (one on the arterial side and one on the venous side of the blood flow circuit) of the connectors 106, 128 can separately travel away from the blood tubing 108, 126 back towards the dialysis machine 200 where they eventually terminate and connect to a conductivity detection circuit, such as the conductivity circuit shown in FIG. 37. The conductivity circuit then provides an appropriately configured signal to the dialysis machine's processor to determine whether a change in fluid conductivity consistent with access disconnection has occurred. If a change in fluid conductivity has occurred, the processor can trigger an alarm condition or initiate a shutdown of the blood pump 13, triggering a mechanical closure of the blood tubing 108 and / or 126, for example.

[0190] Wires running together or separately between the dialysis machine and the patient run the risk of becoming tangled, broken or severed. Therefore, preferably, each wire 326 or 426 can be attached, fused or otherwise incorporated into its associated tubing 108, 128. Incorporating the wire into its associated tubing provides a convenient way of protecting the wire and connections and simplifying the interface between the patient and the dialysis machine. An exemplary method of accomplishing this is shown in Figures 44A-44D. In a preferred embodiment, the tubing is constructed from a flexible material (e.g., silicone) that can be formed in an extrusion process. As shown in Figure 44A, an open wire mesh can be embedded into the flexible silicone tubing as it is formed and extruded, similar to the fiber reinforcement of the flexible tubing. As shown in Figure 41A, a wire mesh 500 can be embedded into the wall of the flexible tubing 502 during extrusion in a manner similar to the construction of the fiber reinforced tube. As shown in Figure 44B, an insulated wire 504 can be bonded to the outer surface of the adjacent tubing 506 during the secondary extrusion process or during a process where the two structures are bonded, for example with an adhesive. As shown in Figure 44C, a secondary extrusion producing a secondary coaxial layer of tubing material 508 can be performed to capture the wire running along the outer surface of the tubing after the primary extrusion. As shown in Figure 44D, the tubing 502 being formed can also be co-extruded with the wire 504 embedded in the wall of the tubing.

[0191] In some of the above methods, the resulting tube-wire combination may tend to kink due to different coefficients of thermal expansion between the wire and the silicone material of the tubing. When the material cools after extrusion, the silicone may tightly trap the embedded wire, causing the cooled tube-wire bundle to kink. In a preferred embodiment, the wire lumen of the extrusion die is configured to be large enough to accommodate a cross-sectional area significantly larger than that of the embedded wire. Then, as the silicone cools, the passage surrounding the wire does not shrink to the extent that it encases the wire tightly. A co-extrusion process incorporating insulated wires can produce a tube-wire bundle as shown in FIG. 45. In this example, the flexible tube 502 is a co-extrusion of a fluid carrying lumen 601 and a wire carrying lumen 602. Preferably, the wire 501 is multi-stranded for flexibility and durability, and is coated or covered with a durable flexible synthetic insulating material 503, such as PTFE. The PTFE-based sheath 503 of the stranded wire 501 can withstand the high temperatures associated with the silicone tubing extrusion process, thereby maintaining its integrity along the portion 504 of the wire that ultimately exits the tubing for connection to either the dialysis machine 200 or the patient line connector 106, 128. The coating or covering can also help prevent the wire from sticking to the sidewalls of the wire carrying lumen after extrusion and during cooling.

[0192] FIG. 46 shows a cross-sectional view of an exemplary connector-wire-tubing assembly. The proximal tubing connection end of connector 400 is shown with an end of dual lumen tubing 502 attached. A fluid carrying lumen 601 is press-fit and / or cemented into the proximal end of connector 400 to allow fluid flow through central lumen 414 of connector 400. Stranded wire 501 is soldered or otherwise attached to electrode 424, which is in conductive contact with fluid present within lumen 414 of connector 400. The unconnected portion of wire 501 that runs outside of tubing 502 is preferably coated with an insulating synthetic coating, such as, for example, PTFE. Optionally, this portion of both exposed and coated wire can also be sealed with a sealant, such as RTV. Coated wire 503 enters wire carrying lumen 602 of tubing 502 near its termination into connector 400. The wire / tubing bundle then travels to the dialysis machine 200 where the wires emerge from the tubing for connection to a conductivity circuit such as the one shown in FIG.

[0193] FIG. 47 shows an exemplary extracorporeal circuit 210 that can be used as a removable replaceable unit in a hemodialysis machine 220 as shown in FIG. 48. In this embodiment, the extracorporeal circuit includes a blood pump cassette 13, a dialyzer 14, a venous return air trap 122, an arterial blood tubing 108, a venous blood tubing 126, an arterial catheter connector 106, and a venous catheter connector 128. The arterial connector 106 and the venous connector 128 may be of a type similar to the connector 300 shown in FIGS. 41A and 41B, or may be of a type similar to the connector 400 shown in FIGS. 43A-43C, or may be a variation thereof. The arterial blood tube 108 and the venous blood tube 126 may be of a type shown in FIGS. 44A-44D or FIG. 45. The wires that form the terminal connections to the electrodes of connectors 106 and 128 exit arterial tubing 106 and venous tubing 126 as segments 504A and 504B to connect with connectors that ultimately pass the connections to terminals associated with a conductivity circuit in the dialysis machine, such as that shown in Figure 37. In the illustrated embodiment, connector 526 is mounted to support structure 214 for blood pump 13 and air trap 122.

[0194] FIG. 48 shows an exemplary hemodialysis machine 220 configured to receive the extracorporeal circuit 210 shown in FIG. 47. In this example, the dialyzer 14 is already mounted on the machine 220. A base 227 receives the control port of the mating blood pump cassette 13. A set of raceways or tracks 225 serve to organize the pair of arterial blood tube 106 and venous blood tube 126 when not extended and connected to a patient. A connector 224 receives the connection made between wire segments 504A and 504B and a connector 526 and passes it to a terminal connection of a conductivity circuit such as that shown in FIG. 1. A tubing closure 226 is positioned to receive the venous blood tube 126 after it exits the air trap 122 and the arterial blood tube 108 after it reaches the blood pump cassette 13. The closure 226 can be pneumatically or electromechanically actuated, for example, whenever an alarm condition occurs that requires the cessation of extracorporeal blood flow. A set of arms of the closure 226 can be configured to rotate against the wall of the flexible tube to inhibit or stop fluid flow therein. Thus, a controller installed in the device 220 can receive a signal from a conductivity circuit similar to that of FIG. 37, which signal represents the electrical resistance of the column of fluid or blood between the electrodes installed in the connectors 106 and 128. Because the connectors are positioned fluidly much closer to the patient's blood vessel or fistula 134 than the blood pump 13, the dialyzer 14 and the air trap 122, the signal related to the fluid path through the vessel or fistula 134 can distinguish between an intact column of blood or fluid and an interrupted column between the connector 106 / 128 and the patient's blood vessel or fistula 134. The controller can be programmed to respond to electrical resistance detected by the conductivity circuit being found to exceed a predetermined value. Depending on the circumstances, the controller can then trigger an alarm to warn the patient against possible disconnection of blood flow, and can also optionally command the closure 226 to stop extracorporeal flow to and from the patient. Disconnection detection circuit operation Figure 49 shows test results utilizing the disconnection detection circuit described above and shown in Figure 37. In this case, a hemodialysis blood circuit and device similar to those disclosed in U.S. Patent Application Publication Nos. 2009 / 0114582 and 2010 / 0056975, the contents of which are incorporated herein by reference, was employed. The extracorporeal circuit 210 shown in Figure 47 includes a blood pump 13, a dialyzer 14, an air trap 122, venous blood circuit tubing 126, and arterial blood circuit tubing 108. The extracorporeal circuit 210 fits into a hemodialysis machine 220 similar to that shown in Figure 48. The blood flow circuit tested included a pair of membrane-based blood pumps disposed in a blood pump cassette 13 shown in FIG. 47, a dialyzer 14, a venous return air trap 122, an arterial blood tubing set 108, a venous blood tubing set 126, an arterial connector 106 and a venous connector 128, and a catheter tubing set 104, 130 connected to vascular access needles 102, 132 as shown in FIG. 40. The needles 102, 132 were disposed in a container holding anticoagulated bovine blood. The blood tubing sets 108 and 126 were approximately 6 feet long and the catheter tubing sets 104 and 130 were approximately 2 feet long or less. The needles were alternately placed in the container and withdrawn from the container into the bloodstream to simulate fistula or disconnection of the needle from the blood vessel. Periods A, C, and F in FIG. 49 represent the time the needles were immersed in blood in the container. The electrical resistance measured by the disconnection detection circuitry shown in FIG. 37 during these periods averaged between 120,000 and 130,000 ohms. Periods B and E in FIG. 49 represent the time when the venous return needle 132 (under positive pressure from the blood pump) is withdrawn from a few centimeters above the surface of the blood in the container, forming a stream of blood mixed with air as it exits the venous return needle and enters the container of blood below. The electrical resistance measured during these periods averaged between 140,000 and 150,000 ohms. Period D represents the time when one of the needles is completely removed from the container, creating a completely open electrical circuit. The electrical resistance measured during this period averaged between approximately 160,000 and 180,000 ohms.Thus, the controller can be easily programmed to identify the difference in the monitored resistance of the electrical circuit between uninterrupted and interrupted flow of blood. These results show that interruption of the continuity of blood between the arterial needle 102 and the venous needle 132 can reliably result in a detectable change in the measured electrical resistance between the two electrodes when placed relatively closer to the arterial and venous access sites than the blood processing components 13, 14 and 122 of the external blood circuit. Furthermore, even a partial interruption of the continuity of blood flow (such as the flow of blood through air) can be reliably detected, even if the change in the measured electrical resistance is small. closure part As discussed above, closures, such as closure 513 of Figure 17, can be used to control flow through lines of a blood circuit assembly, for example, at points between the patient connections of blood lines 203, 204 and other parts of the assembly. Various aspects of the invention related to closures, which may be employed alone or in any suitable combination with other features described herein, are described below in conjunction with one or more specific embodiments.

[0195] According to one aspect of the disclosed invention, a closure assembly is described for compressing at least one flexible tube, e.g., a pair of flexible tubes. The closure assembly comprises a tube closure section comprising a mechanism configured to close off fluid flow in one or more flexible tubes, in some embodiments one or more pairs of flexible tubes. In some embodiments, the tube closure section of the closure assembly comprises at least one closure member, and in specific embodiments, a closure member for each section of tubing disposed in the assembly. In some such embodiments, each closure member is pressed or otherwise forced or biased to a closed position by an element that slides along the side of the closure member, causing the closure member to pivot at its proximal end and translate at its distal end toward the tubing. In one embodiment, the element is positioned between the two closure members and acts to spread the distal ends of the closure members away from each other as the closure members press against their respective tubes. In a preferred option, a main spring urges the spreading element toward the distal end of the closure element to the closed position. The spreading element can be moved against the bias of the main spring to an unclosed position near the proximal end of the closure element, either manually through a button and linkage assembly coupled to the spreading element, or under the control of a controller that activates an actuator also coupled to the spreading element. A hinged door can be configured to cover the closure element and their respective portions of the tubing. Activation of the actuator can be prevented if the door does not properly close on the closure element. Optionally, a retainer element can be enabled to hold the spreading element in the unclosed position when the door is in the open position. Enabling the retainer element allows the spreading portion to be held in the unclosed position without a user applying continuous force to the button or continuous activation of the actuator. The retainer element can be disabled when the door is closed, allowing the spreading element to be freely moved in and out of the closed position, either manually or through the actuator.

[0196] Figures 50 and 51 show exploded perspective views of a closure assembly 700 according to an embodiment of the present disclosure. Figure 50 shows an exploded perspective view of the closure assembly 700 from a front angle, and Figure 51 shows an exploded perspective view of the closure assembly 700 from a rear angle.

[0197] The closure assembly 700 is configured to receive a pair of tubes 705 and close the tubes 705 using a pinching action at approximately the same level along the length of the assembly 700. The pinching action reduces the size of the internal fluid passageway of each tube 705 to restrict the flow of fluid therethrough. The closure assembly 700 can be used in infusion pumps and dialysis machines, hemodialysis, peritoneal dialysis, hemofiltration, hemodiafiltration, enteric dialysis, and the like.

[0198] The closure assembly 700 comprises a frame 701. In some embodiments, the frame 701 comprises tabs or snaps 709 that secure the frame to corresponding slots in a front panel of a blood filtration device, such as a hemodialysis machine.

[0199] The frame 701 includes anvils or blocks 702 and 703 against which a tube 705 is compressed by closed ends 713 of a pair of closure arms 710 and 711, and a tube guide 704 that positions each tube 705 relative to the blocks 702 and 703. The tube guide 704 and blocks 702 and 703 are each configured to position the tube 705 at a predetermined position adjacent each of the blocks 702 and 703. The closure assembly 700 also includes a door 706 that is pivotally mounted to the frame 701. The door 706 is closeable relative to the frame 701 to secure the tube 705 between each of the blocks 702 and 703 and the tube guide 704. The door 706 is integrally molded with a latch 707 through a resiliently flexible base (e.g., via a living hinge) 708 that secures the door 706 to the frame 701 in a closed position. However, the latch 707 may be arranged in other suitable manners, such as including a latch element that is glued, welded, bolted or otherwise attached to the door 706. As shown in Figures 50, 52 and 53, the latch 707 may be pressed laterally to release the catch 740 from engagement with a corresponding slot 741 in the frame 701 to open the door 706.

[0200] The closure assembly 700 comprises two arms 710 and 711. The first arm 710 has a pivot end 712 and a closed end 713, and similarly the second arm 711 has a pivot end 714 and a closed end 715. The two arms 710 and 711 act together to close the tube 705 when a button 716 is released and the door 706 closes or when an actuator 717 is deactivated.

[0201] FIG. 52 shows a front perspective view of the closure assembly 700 with the door 706 open and the button 716 pressed, showing the release of the closure arms 710 and 711 to allow loading and unloading of the tubes 705, according to one embodiment of the present disclosure. FIG. 54 shows the front of the closure assembly 700 of FIG. 50 without the door 706 and frame 701, showing the arms 710 and 711 fully closing the tubes 705a, b, according to one embodiment of the present disclosure. As shown in FIG. 54, the wedge element or flare 722 contacts the facing side of the closure arms 710 and 711, and the closure arms 710 and 711, under spring force, can apply pressure to the closure arms 710 and 711, such that the closed ends 713 and 715 of the closure arms 710 and 711 are pressed against a portion of the tubes 705a, 705b. A user can release the closure arms 710 and 711 by pressing button 716, which causes the spreader 722 to retract away from the closure arms 710 and 711, relieving the spreader 722 pressure applied to the distal ends of the closure arms 710 and 711. In some embodiments, the manual actuator (e.g., button 716) acts as an override mechanism for an automatic actuator (e.g., a pneumatically operated piston / cylinder device, etc.) connected to the line closure element (e.g., spreader 722). The manual actuator is operatively coupled to the line closure to provide a generally linear movement of at least a portion of the line closure to move the closure member from a closed position to an unclosed position upon manual operation of the override mechanism by a user.

[0202] Similarly, actuation of the actuator can release the closure arms 710 and 711 by retracting the flared portion 722 away from the closed ends 713, 715 of the closure arms 710 and 711. In one embodiment, as shown in FIG. 50, the flared portion 722 can be formed from, molded integrally with, attached to, or otherwise connected to a carriage assembly 723, which is further connected to an actuation arm of the actuator (see, for example, FIGS. 56 and 57). The actuator can comprise, for example, a motor and gear assembly (e.g., a rack and pinion assembly or a worm-type gear assembly), a solenoid, a hydraulic cylinder, or a pneumatic cylinder, among others. In a preferred embodiment, the actuator comprises a pneumatic cylinder 717 that linearly extends an actuation arm comprising a piston arm 742 against a spring force (which in one embodiment can be a coil spring 745 in a cylinder 717 as shown in FIG. 60). As shown in FIG. 60, in a side perspective view of the pneumatically actuated linear actuator 717, a piston arm 742 is connected to a carriage 723. When pneumatically actuated, the actuator 717 extends the piston arm 742, moving the carriage 723 and attached spreader 722 in a direction that retracts the spreader 722 from engagement with the distal ends 713, 715 of the closure arms 710 and 711 (notably, the closure arm 711, frame 701, door 706, block 703 and tube guide 704 have been removed from FIGS. 58-60 for clarity). Preferably, a main spring, external or internal to the cylinder / actuator 717, can apply a biasing force to the piston arm 742 or carriage 723 to move the closure arms 710 and 711 relative to the spreader 722 to a closed position. Upon loss of power or air pressure, the closure arms 710 and 711 default to a closed mode, preventing fluid flow through the tube 705. As shown in the cross-sectional view of the closure assembly 700 in FIG. 60, in one embodiment, a coil spring 745 can be disposed within a cylinder 743 to provide a biasing force against which a piston 744 can move a piston arm 742 under air pressure.Air pressure may be supplied to the linear actuator 717 from a pressure source (eg, a tank pressurized by a pump) that is regulated by an intervening electromechanical valve under the control of an electronic controller.

[0203] As shown in Figures 54 and 59, when the linear actuator 717 is fully retracted, the carriage 723 carries a flare 722 along the facing sides of the closing arms 710 and 711 to rotate them to a closed position. The first arm 710 pivots about its pivot end 712 to press the closing end 713 against the first tube 705a that is restrained by the block 702 (see Figure 54). The second arm 711 pivots about its pivot end 714 to allow the closing end 715 to press against the second tube 705 that is restrained by the block 703.

[0204] 55 and 58 show the closure assembly 700 in an unclosed state (frame 701, door 706, blocks 702, 703 and other elements have been removed for clarity). When button 716 is pressed or linear actuator 717 is actuated, carriage 723 and attached extension 722 move distally away from actuator 717, allowing closure arms 710 and 711 to rotate about pivot points 712 and 714 to an unclosed position. The resilience of tubes 705a,b allows arms 710 and 711 to pivot towards one another. In some embodiments of the present disclosure, small magnets (not explicitly shown) embedded in arms 710 and 711 pull arms 710 and 711 towards one another, facilitating retraction of closed ends 713 and 715 away from tube 705. In other embodiments, a small spring (not shown) can bias the closing arms 710 and 711 to pivot toward each other, the spring constant being weak enough to be overcome by a main spring (e.g., spring 745) biasing the carriage 723 or the splay portion 722 to the retracted (closed) position.

[0205] Figure 53 illustrates a side perspective view of the closure assembly 700 of Figure 50 (with frame 701 removed for clarity) showing how the door 706 engages the switch 720 when closed, according to one embodiment of the disclosure. As shown in Figure 53, the hinged portion 708 of the latch 707 is coupled to an engagement member or catch 740 that can fit within an interlocking slot 741 in the frame 701 (see, e.g., Figures 50 and 53). When the door 706 is closed, a portion of the catch 740 of the latch 707 of the door 706 engages the spring loaded switch 720, which in one embodiment includes a spring arm 737 of the switch 720.

[0206] Engagement of switch 720 by closing door 706 notifies an electronic controller (not shown) that door 706 is properly closed and that it may activate linear actuator 717 to release closures 710 and 711 to allow fluid to flow through tubing 705. The door 706 closed signal may also cause the controller to perform other functions, such as commanding a pump coupled to tubing 705 to begin pumping the fluid in tubing 705.

[0207] FIG. 56 shows the rear of the closure assembly 700 of FIG. 50 with the linear actuator 717 in a fully retracted position (i.e., closed position) according to one embodiment of the disclosure. FIG. 56 shows the rear of the closure assembly 700 in the same configuration as shown for the front view of the closure assembly 700 in FIG. 54. FIG. 56 shows some of the actuating parts of the closure assembly 700 of FIG. 50 to illustrate the operation of the actuator 717 and the carriage 723 according to one embodiment of the disclosure. The carriage 723 moves by extension or retraction of the piston arm 742 or by actuation of the button 716. The carriage 723 includes a guide 724 integrally molded or otherwise attached to the carriage 723. The guide 724 guides the carriage 723 as it moves via actuation of the piston arm 742 or by actuation of the button 716. The guide 724 interfaces with a track 725 of the frame 701 (see, for example, FIG. 51).

[0208] In any embodiment, once the door 706 is open, actuation of the button 716 by the user or the actuator 717 by the controller can move the carriage 723 and the extension 722 to an unclosed position, where a retainer element or assembly can hold the unclosed position without further force being applied by the user or by the actuator 717. In the exemplary embodiment shown in FIG. 56, the carriage 723 can incorporate a latch pin 726 that interfaces with a slot or hole in the retaining member 718. The retaining member 718 has a surface 727 positioned for contact by a pin 738 located on the inside of the closed door 706 (see, e.g., FIGS. 51 and 52). A through hole 739 allows the pin 738 to contact a portion of the retaining member 718 to displace it in a rearward direction. In the illustrated embodiment, the pin 738 contacts the front plate 727 of the retaining member 718. The retaining member 718 also has a surface with a slot or hole 729 positioned to receive the head of the latch pin 726, which in the illustrated embodiment comprises a horizontal plate 728 forming a receiver 729. The retaining member 718 is configured to slide within a groove or guide (not shown) in the frame 701 in response to contact by a pin 738 when the door 706 is closed or opened (see, for example, FIG. 51 ). A spring 730 mounted to the frame 701 can bias the retaining member 718 to move forward against a stop feature (not shown) in the frame 701, such that opening the door 706 allows the retaining member 718 to slide forward, realigning the receiver 729 with respect to the latch pin 726. When the door 706 is closed (see Figures 50 and 51), the pin 738 of the door 706 presses against the front plate 727, which compresses the spring 730, thereby positioning the receiver 729 of the horizontal plate 728 directly over the latch pin 726. When the receiver 729 is aligned with the latch pin 726, the area of ​​the receiver 729 is large enough to allow the latch pin 726 to be released by the retaining member 718, thereby allowing the carriage 723 to receive the spring force of the main spring 745 in the actuator 717.Thereafter, when air pressure is not applied to the actuator 717, the carriage 723 is free to move to the closed position. With the retaining member 718 in a disabled (i.e., non-operated) state, the latch pin 726 is free to move through the receiver 729 as the carriage 723 moves between the fully extended and fully retracted positions.

[0209] 57 is a rear view of the closure assembly 700 with the actuator 717 actuated and the piston arm 742 in an extended position to unclose the closure arms 710, 711. In this view, the head of the latch pin 726 is shown above the plane of the horizontal plate 728 of the retaining member 718 and the recessed area 731 of the latch pin 726 is shown aligned with the receiver 729 of the retaining member 718. In this view, the door 706 is in the closed position, which means that the receiver 729 is far enough back that the latch pin 726 does not hang in the retaining member 718.

[0210] When the door 706 is fully open, the pin 738 of the door 706 does not press against the front plate 727 and the spring 730 applies a force to the front plate 727 such that the receiver 729 of the retention member 718 is positioned so that the latch pin 726 can engage an edge of the receiver 729 and hang on the retention member 718. When the receiver 729 is positioned to hang on the latch pin 726, the latch pin 726 moves into the receiver 729 and pulls the front plate 727 rearward against the force of the spring 730. When the head of the latch pin 726 moves fully through the receiver 729, a recessed area 731 below the head of the latch pin 726 is mutually aligned with the horizontal plate 728 which moves as the edge of the receiver 729 moves into the recessed area 731 under the force of the spring 730 applied to the front plate 727. When the pin 738 of the door 706 is fully engaged with the front plate 727, the receiver 729 is positioned to release the latch pin 726 from the latch 718. Thus, when the door 706 is open, the carriage 723 and the spread 722 can be held in the unclosed position without the continued application of force by the actuator 717 or by a user pressing the button 716. This allows a user to load and unload tubing from the closure assembly 700 without simultaneously applying force to the button 716. However, when the door 706 is closed, the retaining member 718 is no longer operable and, without the continued application of force by the actuator 717 or through the button 716, the carriage 723 and the spread 722 move into place to rotate the closure arms 710 and 711 to the closed position.

[0211] 58 and 59 show side perspective views of some of the working parts of the closure assembly 700 of FIG. 50, with the frame 701, blocks 702, 703, tube guide 704, door 706, closure arm 711 and other parts removed for clarity. In FIG. 58, the piston arm 742 is fully extended according to an embodiment of the present disclosure. FIG. 58 shows the latch pin 726 hanging on the retaining member 718. That is, assuming the door 706 is in the open position, the horizontal plate 728 is positioned by the force of the spring 730 to engage the recessed area 731 of the latch pin 726.

[0212] FIG. 59 shows a side perspective view of the closure assembly 700 of FIG. 50 with the piston arm 742 in a fully retracted position, with some elements removed as in FIG. 58 for clarity. In this example, the latch pin 726 is shown fully removed from the retaining member 718, and since there is no actuating force on the actuator 717 or pressing force on the button 716, the piston arm 742, carriage 723 and spreader 722 are free to retract under the force of the main spring 745 (see FIG. 60) biased against the extension of the piston arm 742. The spreader 722 then moves towards the closed ends 713, 715 of the closure arms 710, 711. In one embodiment, as shown in FIGS. 58 and 59, when the button 716 is pressed, it pivots about a pivot axis 732 to raise the lever arm 733. The lever arm 733 is pivotally connected to a connecting member 734 through a proximal pivot axis 735. The connecting member 734 is then pivotally connected to the carriage 723 through a distal pivot axis 736. When the button 716 is pressed or the piston arm 742 moves the carriage 723 towards the retaining member 718, the connecting member 734 moves with the carriage 723 and rotates the button 716 about the pivot axis 732, as shown in FIG.

[0213] Figure 61 illustrates the closure assembly 700 of Figure 50 used in a front panel assembly 911 of a dialysis system according to one embodiment of the disclosure. The closure assembly 700 closes the flexible tubes 901, 902 through which blood flows to and from the patient. The right tube 902 carries blood from the patient to the blood pump assembly 1000 (arterial blood line) and the left tube 901 carries blood from the dialysis machine 14 back to the patient after passing through the air trap 19 (venous blood line). The closure assembly 700 can close the flow of blood through both of these patient tubes 901, 902 simultaneously.

[0214] As described in detail above, the tubes 901, 902 are connected to a blood pump cassette or assembly 1000, which is a modular unit that can be mounted to and removed from the front panel 911. Both patient tubes 901, 902 can be provided as an assembly including the blood pump cassette 1000 and the air trap 19, which can be loaded into the closure assembly 700 when the blood pump cassette 1000 is mounted to the front panel 911. In this embodiment, the closure assembly 700 forms a permanent part of the front panel 911.

[0215] When the closure assembly 700 is in the unclosed state, a pump located in the blood pump cassette 1000 can be activated to pump blood from the patient through the right tubing 902, through the blood pump and through the dialyzer 14. The blood that is processed by the dialyzer 14 then returns to the patient through tubing 901 after first passing through the air trap 19 and the air-in-line detector 823.

[0216] The following are each incorporated herein by reference in their entirety: U.S. Provisional Patent Application No. 60 / 903,582, filed Feb. 27, 2007, entitled "Hemodialysis Systems and Methods," U.S. Provisional Patent Application No. 60 / 904,024, filed Feb. 27, 2007, entitled "Hemodialysis Systems and Methods," U.S. Provisional Patent Application No. 11 / 787,213, filed Apr. 13, 2007, entitled "Heat Exchange Systems, Devices and Methods," U.S. Provisional Patent Application No. 11 / 787,213, filed Apr. 13, 2007, entitled "Fluid Pumping Systems, Devices ... No. 11 / 787,212, filed April 13, 2007, entitled "Thermal and Conductivity Sensing Systems, Devices and Methods," U.S. patent application Ser. No. 11 / 787,112, filed April 13, 2007, entitled "Thermal and Conductivity Sensing Systems, Devices and Methods," U.S. patent application Ser. No. 11 / 871,680, filed October 12, 2007, entitled "Pumping Cassette," U.S. patent application Ser. No. 11 / 871,712, filed October 12, 2007, entitled "Pumping Cassette," U.S. patent application Ser. No. 11 / 871,787, filed October 12, 2007, entitled "Pumping Cassette," No. 11 / 871,793, filed Oct. 12, 2007, entitled "Cassette System Integrated Apparatus," and U.S. patent application Ser. No. 11 / 871,803, filed Oct. 12, 2007, entitled "Cassette System Integrated Apparatus." Additionally, the following are incorporated herein by reference in their entireties:No. 4,808,161 issued on February 28, 1989, entitled "Pressure-Measurement Flow Control System," U.S. Pat. No. 4,826,482 issued on May 2, 1989, entitled "Enhanced Pressure Measurement Flow Control System," U.S. Pat. No. 4,976,162 issued on December 11, 1990, entitled "Enhanced Pressure Measurement Flow Control System," U.S. Pat. No. 5,088,515 issued on February 18, 1992, entitled "Valve System with Removable Fluid Interface," and U.S. Pat. No. 5,088,515 issued on February 18, 1992, entitled "Peritoneal Dialysis Systems Employing a Liquid Distribution and Pumping Cassette that Emulates Glavity Flow." No. 5,350,357, issued Sep. 27, 1994, entitled "Sensor Apparatus Systems, Devices and Methods," now U.S. Patent Application Serial No. F63, filed on the same day herewith, and U.S. Patent Application Serial No. 12 / 038,474, entitled "Cassette System Integrated Apparatus," now U.S. Patent Application Serial No. F62, filed on the same day herewith.

[0217] Although various embodiments of the present invention have been described and illustrated herein, those skilled in the art may readily envision various other means and / or structures for performing the functions described herein and / or obtaining the results and / or one or more advantages described herein. Such envisioning and / or variations are deemed to be within the scope of the present invention. That is, those skilled in the art may readily recognize that all parameters, dimensions, materials, and configurations described herein are exemplary, and that the actual parameters, dimensions, materials, and / or configurations will depend on the specific application in which the present invention is utilized. Those skilled in the art may recognize, with the aid of experimentation, many equivalents to the specific embodiments of the present invention described herein. It should therefore be understood that the above-described embodiments are merely exemplary, and that the present invention may be practiced within the scope of the appended claims and their equivalents.

[0218] The indefinite articles "a" and "an," as used in the specification and claims, should be understood to mean "at least one," unless clearly indicated to the contrary. 1. A drainage cassette connectable to and disconnectable from a front panel of a dialysis unit by a user of the dialysis unit, a venous connection port adapted to be connected to and in fluid communication with a venous blood line connector that is the end point of a venous line of the blood circuit assembly; an arterial connection port connected to an arterial blood line connector that is an end point of an arterial line of the blood circuit assembly and in fluid communication with the arterial blood line connector; a fluid channel fluidly connecting the venous access port and the arterial access port; a drainage outlet port in fluid communication with the fluid channel and configured to removably couple to a drainage connector on the front panel of the dialysis unit; a valve configured to control flow in the fluid channel; The drainage cassette is removable from the front panel, and the valve is configured to be controlled in the fluid channel to controllably open and close fluid communication of the fluid channel between the drainage outlet port and the venous connection port, or to controllably open and close fluid communication of the fluid channel between the drainage outlet port and the arterial connection port. 2. The drainage cassette described in 1., further comprising a body forming the arterial and venous connection ports and the fluid channel. 3. The drainage cassette of 1., further comprising a check valve configured to allow flow out of the fluid channel and out of the drainage outlet port and to prevent flow from the drainage outlet port to the fluid channel. 4. The valve is a pneumatically controlled valve; The drainage cassette described in 1. further comprising an air pressure control port configured to detachably mate with a port on the front panel, the air pressure control port being fluidly connected to the valve to enable control of the valve by the dialysis unit. 5. The drainage cassette described in 1., further comprising a latch configured to releasably lock the drainage cassette to the front panel. 6. The drainage cassette described in 1., wherein the drainage outlet port is in fluid communication with the fluid channel at a point above where the arterial connection port and the venous connection port communicate with the fluid channel. 7. The drainage cassette described in 1., wherein the fluid channel is U-shaped. 8. A drainage cassette as described in 7., wherein the arterial connection port and the venous connection port are fluidly connected to the fluid channel at the ends of the U-shape, and the drainage outlet port is fluidly connected to the fluid channel at the central bend of the U-shape. 9. The drainage cassette described in 1., further comprising a conductivity sensor configured to detect the conductivity of fluid in the fluid channel. 10. The drainage cassette of claim 1, further comprising a temperature sensor configured to detect the temperature of the fluid in the fluid channel. 11. The drainage cassette described in 1., further comprising one or more sensors configured to detect characteristics of the fluid in the fluid channel, the one or more sensors being connected to the electrical connector. 12. The electrical connector is configured to electrically connect the one or more sensors to a corresponding electrical connector on the front panel; Optionally, the electrical connector and the drain outlet port are configured to simultaneously couple with corresponding electrical connectors and drain connectors on the front panel of the dialysis unit in a single connection operation; the valve is a pneumatically controlled valve; The cassette comprises: 11. The drainage cassette described in claim 11, further comprising an air pressure control port configured to detachably mate with a control port on the front panel, the air pressure control port configured to simultaneously couple with a corresponding control port in a single connection operation. 13. The drainage cassette described in 1., wherein the drainage outlet port is permanently open and in fluid communication with the arterial connection port, and the valve is configured to controllably open and close fluid communication in the fluid channel between the drainage outlet port and the venous connection port. 14. The drainage cassette described in 1., wherein the drainage outlet port is permanently open and in fluid communication with the venous connection port, and the valve is configured to controllably open and close fluid communication in the fluid channel between the drainage outlet port and the arterial connection port. 15. A blood circuit assembly and drainage cassette for a dialysis unit, the blood circuit assembly comprising: a pair of pneumatic pumps for circulating blood received from a patient through a circuit including a dialyzer unit and returned to the patient, the pair of pneumatic pumps having pneumatic control ports configured to align and mate with corresponding ports located on a front panel of the dialysis unit by mounting the blood circuit assembly to the front panel and pressing the control ports into engagement with the corresponding ports; an air trap configured to remove air from blood circulating within the circuit; a pair of dialyzer connections configured to connect to an inlet and an outlet of a dialyzer unit; a pair of blood line connectors including an arterial blood line connector that receives blood from the patient and provides blood to the pneumatic pump, and a venous blood line connector that returns blood to the patient; The drainage cassette comprises: a venous connection port connected to the venous blood line connector and in fluid communication with the venous blood line connector; an arterial connection port connected to the arterial blood line connector and in fluid communication with the arterial blood line connector; a fluid channel fluidly connecting the venous access port and the arterial access port; a drain outlet port in fluid communication with the fluid channel and configured to removably couple to a drain connector on a front panel of the dialysis unit; a valve configured to control flow in the fluid channel; The blood circuit assembly and the drainage cassette are both engageable with the front panel for operation in dialysis therapy and removable from the front panel for replacement. 16. The blood circuit assembly and cassette described in 15., wherein the valve is configured to be controlled in the fluid channel to controllably open and close fluid communication of the fluid channel between the drain outlet port and the venous connection port, or to controllably open and close fluid communication of the fluid channel between the drain outlet port and the arterial connection port. 17. The blood circuit assembly and cassette described in 15., further comprising a body forming the arterial and venous connection ports and the fluid channels. 18. The blood circuit assembly and cassette described in 15., further comprising a check valve configured to allow flow out of the fluid channel and out of the drain outlet port and to prevent flow from the drain outlet port to the fluid channel. 19. The valve is a pneumatically controlled valve; 16. The blood circuit assembly and cassette described in claim 16, further comprising an air pressure control port configured to detachably mate with a port on the front panel and fluidly connected to the valve to enable control of the valve by the dialysis unit. 20. The blood circuit assembly and cassette of claim 15, further comprising a latch configured to releasably lock the drainage cassette to the front panel. 21. The blood circuit assembly and cassette described in 15., wherein the drain outlet port is in fluid communication with the fluid channel at a point above where the arterial connection port and the venous connection port are in communication with the fluid channel. 22. The blood circuit assembly and cassette described in 15., wherein the fluid channel is U-shaped. 23. The blood circuit assembly and cassette described in 22., wherein the arterial connection port and the venous connection port are fluidly connected to the fluid channel at the ends of the U-shape, and the drain outlet port is fluidly connected to the fluid channel at the central bend of the U-shape. 24. The blood circuit assembly and cassette described in 15., further comprising a conductivity sensor configured to detect the conductivity of fluid in the fluid channel. 25. The blood circuit assembly and cassette described in claim 15, further comprising a temperature sensor configured to detect the temperature of the fluid in the fluid channel. 26. The blood circuit assembly and cassette described in 15., further comprising one or more sensors configured to detect a characteristic of the fluid in the fluid channel. 27. The blood circuit assembly and cassette described in 26., wherein the one or more sensors are connected to an electrical connector, and the electrical connector is configured to mate with a corresponding electrical connector on the front panel when the drain outlet port is coupled to the drain connector. 28. The blood circuit assembly and cassette described in 27., wherein the electrical connector and the drain outlet port are configured to simultaneously connect with corresponding electrical connectors and drain connectors on the front panel of the dialysis unit in a single connection operation. 29. The valve is a pneumatically controlled valve; 29. The blood circuit assembly and cassette described in 28., wherein the cassette further comprises a pneumatic control port configured to detachably mate with a control port on the front panel. 30. The blood circuit assembly and cassette described in 15., wherein the drain outlet port is permanently open and in fluid communication with the arterial connection port, and the valve is configured to controllably open and close fluid communication in the fluid channel between the drain outlet port and the venous connection port. 31. The blood circuit assembly and cassette described in 15., wherein the drain outlet port is permanently open and in fluid communication with the venous connection port, and the valve is configured to controllably open and close fluid communication in the fluid channel between the drain outlet port and the arterial connection port.

Claims

1. a drainage cassette connectable to and disconnectable from a front panel of the dialysis unit by a user of the dialysis unit, a venous connection port for connecting to and in fluid communication with a venous blood line connector that is the end point of a venous line of the blood circuit assembly; an arterial connection port connected to an arterial blood line connector that is an end point of an arterial line of the blood circuit assembly and in fluid communication with the arterial blood line connector; a fluid channel fluidly connecting the venous access port and the arterial access port; a drainage outlet port in fluid communication with the fluid channel and configured to removably couple to a drainage connector on the front panel of the dialysis unit; a valve configured to control flow in the fluid channel; The drainage cassette is removable from the front panel, and the valve is configured to be controlled in the fluid channel to controllably open and close fluid communication of the fluid channel between the drainage outlet port and the venous connection port, or to controllably open and close fluid communication of the fluid channel between the drainage outlet port and the arterial connection port.

2. The drainage cassette of claim 1 , further comprising a body defining said arterial and venous connection ports and said fluid channels.

3. 10. The drainage cassette of claim 1, further comprising a check valve configured to allow flow out of the fluid channel and out of the drain outlet port and to prevent flow from the drain outlet port to the fluid channel.

4. the valve is a pneumatically controlled valve; 10. The drainage cassette of claim 1, further comprising an air pressure control port configured to detachably mate with a port in the front panel, the air pressure control port fluidly connected to the valve to enable control of the valve by the dialysis unit.

5. The drainage cassette of claim 1 , further comprising a latch configured to releasably lock the drainage cassette to the front panel.

6. The drainage cassette of claim 1 , wherein the drainage outlet port is in fluid communication with the fluid channel at a point above where the arterial and venous connection ports communicate with the fluid channel.

7. The drainage cassette of claim 1 , wherein the fluid channel is U-shaped.

8. 8. The drainage cassette of claim 7, wherein the arterial connection port and the venous connection port are fluidly connected to the fluid channel at the ends of the U-shape and the drainage outlet port is fluidly connected to the fluid channel at a central bend of the U-shape.

9. The drainage cassette of claim 1 , further comprising a conductivity sensor configured to detect a conductivity of a fluid in the fluid channel.

10. The drainage cassette of claim 1 , further comprising a temperature sensor configured to detect a temperature of fluid in the fluid channel.

11. The drainage cassette of claim 1 , further comprising one or more sensors configured to detect a property of a fluid in the fluid channel, the one or more sensors being connected to an electrical connector.

12. the electrical connector is configured to electrically connect the one or more sensors to a corresponding electrical connector on the front panel; Optionally, the electrical connector and the drain outlet port are configured to simultaneously couple with corresponding electrical connectors and drain connectors on the front panel of the dialysis unit in a single connection operation; the valve is a pneumatically controlled valve; The cassette comprises:

12. The drainage cassette of claim 11, further comprising pneumatic control ports configured to detachably mate with the control ports on the front panel, the pneumatic control ports configured to simultaneously couple with corresponding control ports in a single connection operation.

13. 2. The drainage cassette of claim 1, wherein the drainage outlet port is permanently open and in fluid communication with the arterial connection port, and the valve is configured to controllably open and close fluid communication in the fluid channel between the drainage outlet port and the venous connection port.

14. 2. The drainage cassette of claim 1, wherein the drainage outlet port is permanently open and in fluid communication with the venous connection port, and the valve is configured to controllably open and close fluid communication in the fluid channel between the drainage outlet port and the arterial connection port.

15. The blood circuit assembly, a pair of pneumatic pumps for circulating blood received from a patient through a circuit including a dialyzer unit and returned to the patient, the pair of pneumatic pumps having pneumatic control ports configured to align and mate with corresponding ports located on the front panel of the dialysis unit by mounting the blood circuit assembly to the front panel and pressing the control ports into engagement with the corresponding ports; an air trap configured to remove air from blood circulating within the circuit; a pair of dialyzer connections configured to connect to an inlet and an outlet of a dialyzer unit; the arterial blood line connector receiving blood from the patient and providing blood to the pneumatic pump; a venous blood line connector for returning blood to the patient; 10. The drainage cassette of claim 1 in combination with the blood circuit assembly, wherein both the blood circuit assembly and the drainage cassette are engageable with the front panel for operation in dialysis therapy and detachable from the front panel for replacement.

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