Blood treatment systems and methods

Abstract

To provide a blood treatment system and method that makes hemodialysis more efficient, easier, and / or less expensive. [Solution] The present invention relates to hemodialysis and similar dialysis systems, including various systems and methods for making hemodialysis more efficient, easier and / or less expensive. One aspect of the present invention relates to a novel fluid circuit for fluid flow. According to one aspect, the blood pump comprises a reciprocating diaphragm pump that is pneumatically driven or controlled and configured to deliver blood to the dialysis machine of a hemodialysis machine.

Description

[Technical Field]

[0001] The present invention relates to hemodialysis and similar dialysis systems, such as systems that can treat blood or other body fluids outside the body. In some embodiments, the system includes various systems and methods that make hemodialysis more efficient, easier, and / or less expensive. [Background technology]

[0002] Numerous factors have made hemodialysis inefficient, difficult, and costly. These factors include the complexity of hemodialysis, safety concerns, and the large volume of dialysate required. Furthermore, hemodialysis is typically performed in a dialysis center and requires skilled technicians. Therefore, improvements in the ease and efficiency of the dialysis process can impact treatment costs or patient outcomes.

[0003] Figure 1 is a schematic diagram of a hemodialysis system. System 5 includes two flow paths, namely a blood flow path 10 and a dialysate flow path 20. Blood is drawn from the patient. A blood flow pump 13 ensures that blood flows through the blood flow path 10, drawing blood from the patient's body, passing through the dialysis machine 14, and returning the blood to the patient. Optionally, the blood may pass through other components such as a filter and an air trap 19 before returning to the patient. Furthermore, in some cases, an anticoagulant can be supplied from an anticoagulant supply unit 11 via an anticoagulant valve 12.

[0004] The dialysate pump 15 draws dialysate from the dialysate supply unit 16, allowing it to pass through the dialysate machine 14, after which it can pass through the waste valve 18 and / or return to the dialysate supply unit via the dialysate pump 15. The dialysate valve 17 controls the flow of dialysate from the dialysate supply unit 16. The dialysate machine is a type of filter with a semipermeable membrane, configured such that blood from the vascular circuit flows through very small tubes and dialysate circulates around the outside of the tubes. Treatment is achieved by passing waste molecules (e.g., urea, creatinine, etc.) and water from the blood through the tube walls into the dialysate. At the end of the procedure, the dialysate is discarded. [Overview of the Initiative] [Problems that the invention aims to solve]

[0005] The object of the present invention is to provide various hemodialysis systems and methods as described in the specification. [Means for solving the problem]

[0006] The subject matter of the present invention may, in some cases, include related products, alternative solutions to specific problems, and / or multiple different uses of one or more systems and / or articles. Although the various systems and methods described herein are described in relation to hemodialysis, it should be understood that the various systems and methods described herein are applicable to other dialysis systems and / or any extracorporeal systems capable of treating blood or other body fluids, such as hemofiltration, hemodiafiltration, etc.

[0007] In some embodiments, the present invention relates to a flexible partition wall used in a reciprocating diaphragm pump. The diaphragm pump may comprise a first rigid body having a curved pumping chamber wall and a second rigid body having an opposing curved control chamber wall. The partition wall may be configured to be inserted between the pumping chamber wall and the control chamber wall. In some such embodiments, the partition wall comprises a peripheral bead configured to position the partition wall between the first and second rigid bodies, and a partition wall body having a curved, semi-revolute elliptical, or dome shape, wherein the partition wall body may have a pumping side configured to substantially conform to the curved inner surface of the pumping chamber wall or the curved inner surface of the control chamber wall and positioned to face the inner surface of the pumping chamber wall, and an opposing control side positioned to face the inner surface of the control chamber wall. The partition wall may further comprise a transition region between the bead and the partition wall body, the transition region being positioned to be sandwiched or clamped between a clamping region of the first rigid body and an opposing clamping region of the second rigid body. Such partitions can be pre-formed or molded so that their control side has a convex shape, thereby reducing any elastic tension of the partition when the control side of the partition body exhibits a convex shape when positioned within the diaphragm pump.

[0008] In some embodiments, the present invention relates to a reciprocating diaphragm pump comprising a first rigid body having a pumping chamber wall, a second rigid body having an opposing control chamber wall, and a partition wall configured to be inserted between the pumping chamber wall and the control chamber wall to define the pumping chamber and the control chamber. In some such embodiments, the partition wall comprises a peripheral bead configured to position the partition wall between the first and second rigid bodies, and a partition wall body having a curved, semi-revolute elliptical, or dome shape, wherein the partition wall body is configured to substantially conform to the curved inner surface of the pumping chamber wall or the curved inner surface of the control chamber wall and may have a pumping side positioned to face the inner surface of the pumping chamber wall and a control side positioned to face the inner surface of the control chamber wall. The partition wall may further comprise a transition region between the bead and the partition wall body, the transition region being positioned to be sandwiched or clamped between a clamping region of the first rigid body and an opposing clamping region of the second rigid body. Such partitions can be pre-formed or molded so that their control side has a convex shape, thereby reducing any elastic tension of the partition when the control side of the partition body exhibits a convex shape when positioned within the diaphragm pump.

[0009] In some embodiments, the present invention relates to a pump cassette for pumping fluid. The pump cassette may comprise a first rigid body having a pumping chamber wall, a second rigid body having an opposing control chamber wall, and a partition wall inserted between the pumping chamber wall and the control chamber wall and configured to define the pumping chamber and the control chamber. The pumping chamber can be in fluid communication with a fluid inlet and a fluid outlet of the cassette. The control chamber can be in fluid communication with a pneumatic control port that transmits pneumatic pressure to the control chamber. In some embodiments, the partition wall of such a pump cassette comprises a peripheral bead configured to position the partition wall between the first and second rigid bodies, and a partition wall body having a curved shape, a semi-revolute elliptical shape, or a dome shape, wherein the partition wall body is configured to substantially conform to the curved inner surface of the pumping chamber wall or the curved inner surface of the control chamber wall. The partition wall body may also have a pumping side positioned to face the inner surface of the pumping chamber wall and an opposing control side positioned to face the inner surface of the control chamber wall. The partition may also include a transition region between the bead and the partition body, which is positioned to be sandwiched or clamped between the clamping region of the first rigid body and the opposing clamping region of the second rigid body. Such partitions may be pre-formed or molded so that their control side is convex, thereby reducing any elastic tension of the partition when the control side of the partition body is convex when positioned within the diaphragm pump.

[0010] In one aspect and a set of embodiments, a system for controlling fluid flow in a hemodialysis machine is disclosed. The system comprises a dialysate pump configured to receive fluid from the dialysate outlet of the dialyzer; a reciprocating diaphragm-based blood pump configured to deliver blood from an extracorporeal blood circuit to the blood inlet of the dialyzer, wherein the pumping chamber of the blood pump is separated from the control chamber of the blood pump by a flexible partition, and the control chamber is configured to transmit positive or negative pressure to operate the partition; a pressure sensor configured to measure the pressure in the control chamber of the blood pump; and a controller configured to receive information from the pressure sensor and to control the delivery of pressure to the control chamber of the blood pump, wherein the controller is configured to apply a time-varying pressure waveform to the blood pump partition during the filling stroke of the blood pump and to monitor pressure fluctuations in the control chamber measured by the pressure sensor, and if the magnitude of the measured pressure fluctuations deviates from a predetermined value, the controller initiates a procedure to pause or stop the dialysate pump.

[0011] Some embodiments relate to a system for monitoring fluid flow in an extracorporeal blood circuit, comprising: a pumping chamber of a blood pump separated from a control chamber of the blood pump by a flexible partition, the pumping chamber being configured to transmit positive or negative pressure to cause the control chamber to operate the partition; a pressure sensor configured to measure the pressure in the control chamber of the blood pump; and a controller configured to receive information from the pressure sensor and to control the delivery of pressure to the control chamber of the blood pump, wherein the controller is configured to apply a time-varying pressure waveform to the blood pump partition during the filling stroke of the blood pump and to monitor pressure fluctuations in the control chamber measured by the pressure sensor, and the controller transmits a value representing the magnitude of the measured pressure fluctuations to a display associated with the extracorporeal blood circuit.

[0012] Some embodiments relate to methods for controlling fluid flow in a hemodialysis machine. Such methods may include: a controller receiving information from a pressure sensor in the control chamber of a reciprocating diaphragm-based blood pump; the controller applying a time-varying pressure waveform to the partition wall of the blood pump during the filling stroke of the blood pump; the controller monitoring pressure fluctuations in the control chamber as measured by the pressure sensor; the controller comparing the measured pressure fluctuations to a predetermined value; and the controller initiating a procedure to pause or stop the dialysate pump of the hemodialysis machine if the magnitude of the measured pressure fluctuations deviates from the predetermined value.

[0013] Some embodiments describe a method for monitoring fluid flow in an extracorporeal blood circuit, comprising the steps of: a controller receiving information from a pressure sensor in the control chamber of a reciprocating diaphragm-based blood pump; the controller applying a time-varying pressure waveform to the septum of the blood pump during the filling stroke of the blood pump; the controller monitoring pressure fluctuations in the control chamber as measured by the pressure sensor; and the controller transmitting a value representing the magnitude of the measured pressure fluctuations to a display associated with the extracorporeal blood circuit.

[0014] In one embodiment, a hemodialysis and similar extracorporeal blood treatment system is provided. In some embodiments, such a system includes four fluid channels: one for blood, one for dialysate to the interior, one for dialysate to the exterior, and one for mixing the dialysate. In some embodiments, these four channels are combined in a single cassette. In other embodiments, each of these four channels is located in its own cassette. In yet another embodiment, two or more fluid channels are included in a single cassette.

[0015] In one embodiment, a hemodialysis system is provided having at least two fluid channels, these two fluid channels being incorporated into 1) a blood flow pump cassette, 2) an internal dialysate cassette, 3) an external dialysate cassette, and 4) a mixing cassette. The cassettes can be fluidly connected to one another. In some embodiments, one or more of these cassettes can be combined into a single cassette.

[0016] In another embodiment, a hemodialysis system is also provided, which includes a blood flow channel through which untreated blood is drawn from the patient and passed through a dialysis machine, and treated blood is returned to the patient. The blood flow channel may include at least one blood flow pump located in a removable cassette. The hemodialysis system may also include a first receiving structure for receiving a cassette of blood flow channels, a dialysate flow channel through which dialysate flows from a dialysate supply unit through a dialysis machine, a second receiving structure for receiving a cassette of dialysate flow channels, and a control fluid path for providing control fluid from an actuator mechanism to the cassette to operate the blood flow pump and the dialysate pump, respectively. In some cases, the dialysate flow channel may include at least one dialysate pump located in a removable cassette.

[0017] In yet another embodiment, a hemodialysis system is disclosed. The hemodialysis system in this embodiment includes a blood flow path through which untreated blood is drawn from the patient and passed through a dialysis machine, and treated blood is returned to the patient. The blood flow path may include at least one blood valve. The hemodialysis system may also include a blood valve, a dialysate mixing system fluidly connected to the dialysis machine (which may include at least one dialysis machine valve), and a control fluid path that provides control fluid from an actuator mechanism to the blood valve to actuate a heating means or heater for heating the dialysate.

[0018] In yet another embodiment, a hemodialysis system is disclosed that includes a blood flow path through which untreated blood is withdrawn from a patient and passed through a dialysis device and through which treated blood is returned to the patient. The blood flow path can include at least one blood pump. The hemodialysis system can also include a dialysate flow path through which dialysate flows from a dialysate supply through the dialysis device. The dialysate flow path can include at least one pneumatic pump.

[0019] In one aspect, the present invention relates to a hemodialysis system. In a set of embodiments, the hemodialysis system includes a blood flow path, a first cassette defining an internal dialysate flow path, a dialysis device in fluid communication with the blood flow path and the internal dialysate fluid path, a second cassette defining an external dialysate fluid path, and a filter fluidly connecting the first cassette to the second cassette.

[0020] In another set of embodiments, the hemodialysis system includes a blood flow path, an internal dialysate fluid path, a dialysis device in fluid communication with the blood flow path and the internal dialysate fluid path, an external dialysate fluid path, a filter fluidly connecting the internal dialysate fluid path and the external dialysate fluid path, a first dialysate pump for pumping dialysate through the internal dialysate fluid path, and a second dialysate pump for pumping dialysate through the external dialysate fluid path, the second dialysate pump and the first dialysate pump being operably connected such that the flow through the internal dialysate fluid path is substantially equal to the flow through the external dialysate fluid path.

[0021] In yet another set of embodiments, the dialysate system includes a blood flow path through which blood is withdrawn from a patient and passed through a dialysis device, and a dialysate flow path through which dialysate flows from a dialysate supply through the dialysis device. In some cases, the dialysate flow path includes an equilibrium cassette for controlling the amount of dialysate passing through the dialysis device, a mixing cassette for forming dialysate from water, and a directing cassette for sending water from a water supply to the mixing cassette and sending dialysate from the mixing cassette to the equilibrium cassette.

[0022] In another set of embodiments, the hemodialysis system includes a cassette system comprising a directing cassette, a mixing cassette, and an equilibration cassette. In some cases, the directing cassette can direct water from a water supply to the mixing cassette and dialysis fluid from the mixing cassette to the equilibration cassette. The mixing cassette can mix the water from the directing cassette with dialysis fluid from a dialysis fluid precursor to produce a precursor. The equilibration cassette can control the amount of dialysis fluid passing through the dialysis device.

[0023] In one set of embodiments, the hemodialysis system includes a blood flow path including a blood pump through which blood is withdrawn from a patient and passed through a dialysis device, a dialysis fluid flow path including a dialysis fluid pump through which dialysis fluid flows from a dialysis fluid supply through the dialysis device, and a control flow path including a control fluid path through which a control fluid actuates the blood pump and the dialysis fluid pump.

[0024] In another set of embodiments, the hemodialysis system includes a blood flow path through which blood is withdrawn internally from a patient and passed through a dialysis device, and a dialysis fluid flow path through which dialysis fluid flows from a dialysis fluid supply through the dialysis device. In some cases, the dialysis fluid flow path includes at least one pneumatic pump.

[0025] In yet another set of embodiments, the hemodialysis system includes a first pump having a pumping chamber and an actuating chamber, a second pump having a pumping chamber and an actuating chamber, a control fluid in fluid communication with each of the actuating chambers of the first and second pumps, and a controller capable of pressurizing the control fluid to control the operation of the first and second pumps.

[0026] In yet another set of embodiments, the hemodialysis system includes a first valve comprising a valve chamber and an actuation chamber, a second valve comprising a valve chamber and an actuation chamber, a control fluid in fluid communication with each of the actuation chambers of the first and second valves, and a controller capable of pressurizing the control fluid to control the operation of the first and second valves.

[0027] In one embodiment, the hemodialysis system includes a blood flow path through which blood is drawn from a patient and passed through a dialysis machine; a cassette including at least a portion of the blood flow path; and a spike integrally formed with the cassette, the spike being capable of receiving a fluid vial, and the integrally formed spike being in fluid communication with the blood flow path within the cassette.

[0028] In another embodiment, the hemodialysis system includes a blood channel through which untreated blood is drawn from the patient and passed through a dialysis machine; a dialysis channel through which dialysate flows from a dialysate supply unit through the dialysis machine, the dialysis machine enabling the dialysate to move from the dialysate channel into the blood channel; and a gas supply unit that is in fluid communication with the dialysis channel, thereby, when activated, allowing gas from a gas supply unit to pass the dialysate through the dialysis machine and return the blood in the blood channel to the patient.

[0029] In yet another set of embodiments, the hemodialysis system includes a blood channel through which untreated blood is drawn in from the patient and passed through a dialysis machine; a dialysate channel through which dialysate flows from a dialysate supply unit to a dialysis machine, and through which the dialysis machine enables the dialysate to move from the dialysate channel to the blood channel; a fluid supply unit; a chamber in fluid communication with the fluid supply unit and the dialysate channel, having a partition wall that separates the fluid from the fluid supply unit from the dialysate in the dialysate channel; and a pressurizing device that pressurizes the fluid supply unit to press the partition wall against the dialysate in the chamber, thereby pushing the dialysate through the dialysis machine and the blood in the blood channel back to the patient.

[0030] In yet another set of embodiments, the hemodialysis system includes a blood channel through which untreated blood is drawn from a patient and passed through a dialysis machine; a dialysate channel through which dialysate flows from a dialysate supply unit through the dialysis machine, and through which the dialysate channel and the blood channel are in fluid communication; and a pressure device that can push the dialysate in the dialysate channel into the blood channel.

[0031] In one embodiment, the hemodialysis system includes a first housing containing a positive displacement pump driven by a control fluid, a fluid conduit for fluidly connecting the positive displacement pump to the control fluid pump, and a second housing containing the control fluid pump and being detachable from the first housing.

[0032] In another set of embodiments, the hemodialysis system includes a housing comprising a first compartment and a second compartment separated by an insulating wall, the first compartment being sterilizable at a temperature of at least about 80°C, and the second compartment containing electronic components that are not heated to a temperature above 60°C when the first compartment is heated to at least about 80°C.

[0033] In yet another set of embodiments, the hemodialysis system includes a blood flow path through which untreated blood is drawn from a patient and passed through a dialysis machine, the blood flow path including at least one blood valve, a control fluid path that provides control fluid to the blood valve from an actuator mechanism to actuate the blood valve, a dialysate mixing system fluidly connected to the dialysis machine including at least one dialysis machine valve, and a heater for heating the dialysate.

[0034] Another aspect of the present invention relates to a valve system. In one embodiment, the valve system includes a valve housing housing a plurality of valves, each comprising at least two of the valves having a valve chamber and an operating chamber, and each of the at least two valves being driveable by a control fluid in the operating chamber; a control housing having a plurality of fluid interface ports enabling fluid communication with a control fluid from a base unit; and a plurality of tubes extending between the valve housing and the control housing, each tube enabling fluid communication between one of the fluid interface ports and at least one of the operating chambers, thereby allowing the base unit to actuate the valve by pressurizing the control fluid in the fluid interface port.

[0035] In one embodiment, the present invention relates to a valve comprising: a first plate; a second plate having a recess on the side facing the first plate, with a groove defined inside the recess, the groove opening in the direction facing the first plate; a third plate, the second plate positioned between the first and third plates; and a partition wall positioned in the recess between the first and second plates, having a rim, the rim being held in the groove. The second plate may include a valve seat, the valve seat being positioned such that the partition wall can be pressed against it to close and seal the valve seat by pneumatic pressure, the groove surrounding the valve seat. In some cases, a valve inlet and a valve outlet are defined between the second and third plates. In one embodiment, a passage for supplying pneumatic pressure is defined between the first and second plates.

[0036] A further aspect of the present invention relates to a pumping system. In one embodiment, the pumping system includes a pump housing housing a plurality of pumps, wherein at least two of the pumps each include a pumping chamber and an operating chamber, and each of the at least two pumps is actuated by a control fluid in the operating chamber; a control housing having a plurality of fluid interface ports that enable fluid communication with a control fluid from a base unit; and a plurality of tubes extending between the pump housing and the control housing, each tube enabling fluid communication between one of the fluid interface ports and at least one of the operating chambers, thereby allowing the base unit to actuate the pumps by pressurizing the control fluid in the fluid interface port.

[0037] The present invention relates to a pump cassette in another embodiment. In one embodiment, the pump cassette includes at least one fluid inlet, at least one fluid outlet, a flow path connecting at least one fluid inlet and at least one fluid outlet, and a spike for attaching a vial to the cassette. The spike may optionally be in fluid communication with the flow path.

[0038] In one embodiment, the present invention relates to a pump cassette for balancing flows to and from a target. In one embodiment, the pump cassette includes a cassette inlet, a supply line to a target, a return line from a target, a cassette outlet, a pumping mechanism for causing fluid to flow from the cassette inlet to the supply line and from the return line to the cassette outlet, and a balancing chamber. In some cases, the pumping mechanism includes a pod pump having a rigid curved wall defining a pumping space and having an inlet and an outlet, a pump partition mounted within the pumping space, and an operating port connecting the pod pump to a pneumatic actuation system, thereby driving the partition to allow fluid to enter and exit the pumping space, the pump partition separating the fluid from a gas that is in fluid communication with the pneumatic actuation system. In some cases, the balancing chamber includes a rigid curved wall defining a balancing space and a balancing partition mounted within the balancing space, the balancing partition separating the balancing space into a supply side and a return side, each of which has an inlet and an outlet. In some cases, fluid from the cassette inlet flows to the supply inlet, fluid from the supply outlet flows to the supply line, fluid from the return line flows to the return inlet, and fluid from the return outlet flows to the cassette outlet.

[0039] In another embodiment, the pumping system includes a system inlet, a supply line to a target, a return line from the target, a system outlet, a pumping mechanism that causes fluid to flow from the cassette inlet to the supply line and from the return line to the cassette outlet, and a balancing chamber.

[0040] In one embodiment, the pumping mechanism includes a pod pump having a rigid rotating elliptical wall defining a pumping space and having an inlet and an outlet; a pump partition wall located within and attached to the rotating elliptical wall; and ports connecting the pod pump to a pneumatic actuation system, thereby driving the partition wall to allow fluid to enter and exit the pumping space. In some cases, the pump partition wall separates the fluid from a gas that is in fluid communication with the pneumatic actuation system.

[0041] In some cases, the equilibrium chamber includes a rigid spheroidal wall defining the equilibrium space and an equilibrium partition wall located within and attached to the spheroidal wall. In one embodiment, the equilibrium partition wall separates the equilibrium space into a supply side and a return side, each of which has an inlet and an outlet. In some cases, fluid from the system inlet flows to the supply side inlet, fluid from the supply side outlet flows to the supply line, fluid from the return line flows to the return side inlet, and fluid from the return side outlet flows to the system outlet. The pumping mechanism may also include valve mechanisms located at the inlets and outlets of each of the supply and return sides. The valve mechanisms may be pneumatically actuated.

[0042] A further aspect of the present invention relates to a cassette. In one embodiment, the cassette includes a first channel connecting a first inlet to a first outlet, a second channel connecting a second inlet to a second outlet, a pump capable of dispensing fluid through at least a portion of the second channel, and at least two balancing chambers, each balancing chamber comprising a rigid vessel, the rigid vessel dividing the rigid vessel into a first section and a second section, the first section of each balancing chamber being in fluid communication with the first channel, and the second section being in fluid communication with the second channel.

[0043] In another embodiment, the cassette includes a first flow path connecting a first inlet to a first outlet, a second flow path connecting a second inlet to a second outlet, a control fluid path, and at least two pumps, each pump comprising a rigid vessel, the rigid vessel comprising a partition dividing the rigid vessel into a first compartment and a second compartment, the first compartment of each pump being in fluid communication with the control fluid path, the second compartment being in fluid communication with the second flow path, and a balancing chamber being able to balance the flow between the first and second flow paths.

[0044] In yet another embodiment, the cassette includes a first channel connecting a first inlet to a first outlet, a second channel connecting a second inlet to a second outlet, and a rigid vessel, the rigid vessel including a partition dividing the rigid vessel into a first section and a second section. In some cases, the first section is in fluid communication with the first channel, and the second section is in fluid communication with the second channel.

[0045] A further aspect of the present invention relates to a pump. In one embodiment, the pump includes a first rigid component, a second rigid component having a groove defined on the side facing a first plate, the groove opening in the direction facing the first rigid component, and a partition having a rim, the rim being held in the groove by friction fitting within the groove, but without the first rigid component being in contact with the rim. In some cases, the first and second rigid components define, at least partially, a pod pump chamber divided into separate chambers by the partition, further defining a flow path to the pod pump chamber, and the groove encircles the pod pump chamber.

[0046] In another embodiment, the pump comprises a substantially spherical vessel, the vessel comprising a flexible partition dividing a rigid vessel into a first and a second compartment, the first and second compartments being not in fluid communication with each other, thereby causing the pumping of fluid in the second compartment due to the movement of the partition as fluid enters the first compartment.

[0047] In another set of embodiments, the pump is a reciprocating positive displacement pump. In one embodiment, the pump includes a rigid chamber wall, a flexible partition wall attached to the rigid chamber wall such that the flexible partition wall and the rigid chamber wall define a pumping chamber, an inlet directing flow into the pumping chamber through the rigid chamber wall, an outlet directing flow out of the pumping chamber through the rigid chamber wall, a rigid limiting wall that restricts the movement of the partition wall and limits the maximum volume of the pumping chamber such that the flexible partition wall and the rigid limiting wall form an operating chamber, and a pneumatic actuation system that intermittently provides a control pressure to the operating chamber. In some cases, the pneumatic actuation system includes an operating chamber pressure transducer that measures the pressure in the operating chamber, a gas reservoir having a first pressure, a variable valve mechanism that variably restricts the flow of gas between the operating chamber and the gas reservoir, and a controller that receives pressure information from the operating chamber pressure transducer and controls the variable valve to bring a control pressure into the operating chamber, wherein the control pressure is less than the first pressure.

[0048] A further aspect of the present invention relates to a method. In one set of embodiments, the method includes providing a first pump comprising a pumping chamber and an operating chamber, and a second pump comprising a pumping chamber and an operating chamber, feeding a common fluid into the respective operating chambers of the first and second pumps, and pressurizing the common fluid and feeding it through each of the first and second pumps.

[0049] In another embodiment, the method includes providing a first valve comprising a valve chamber and an actuation chamber, and a second valve comprising a valve chamber and an actuation chamber; introducing a common fluid into the respective actuation chambers of the first and second valves; and pressurizing the common fluid to at least partially prevent the fluid flow from passing through each of the first and second valves.

[0050] In yet another set of embodiments, the method is a method for measuring the clearance of a dialysis machine, the dialysis machine comprising a blood channel through which untreated blood is drawn from the patient and passed through the dialysis machine, and a dialysate channel through which dialysate can flow from a dialysate supply unit through the dialysis machine, wherein the blood channel is separated from the dialysate channel by a membrane of the dialysis machine. In one embodiment, the method includes the act of supplying liquid to the dialysis machine through the dialysate channel to keep the membrane moist and prevent the flow of gas through the membrane, the act of supplying gas to the dialysis machine through the blood channel to fill the blood channel in the dialysis machine with gas, the act of measuring the volume of gas in the dialysis machine, and the act of calculating the clearance of the dialysis machine based on the volume of gas measured in the dialysis machine.

[0051] In yet another set of embodiments, the method is a method for measuring the clearance of a dialysis machine. In one embodiment, the method includes the act of applying a pressure difference across the dialysis machine, the act of measuring the flow rate of the dialysis machine, and the act of determining the clearance of the dialysis machine based on the pressure difference and the flow rate.

[0052] In yet another set of embodiments, the method is a method for measuring the clearance of a dialysis machine. In one embodiment, the method includes passing water through a dialysis machine, measuring the amount of ions collected by the water after it has passed through the dialysis machine, and determining the clearance of the dialysis machine based on the amount of ions collected by the water after it has passed through the dialysis machine. In yet another set of embodiments, the method includes passing water through a dialysis machine, measuring the conductivity of the water, and determining the clearance of the dialysis machine based on the change in the conductivity of the water.

[0053] In one embodiment, the method is a method for introducing a fluid into blood. In one embodiment, the method includes providing a cassette including an integrally formed spike for receiving a fluid vial, and a valve mechanism for controlling the flow of fluid from the vial into the cassette; attaching a fluid vial to the spike; pumping blood through the cassette; and introducing the fluid from the vial into the blood.

[0054] In one embodiment, the method includes providing a hemodialysis system comprising a blood channel through which untreated blood is drawn from a patient and passed through a dialysis machine, and a dialysate channel through which dialysate flows from a dialysate supply unit through a dialysis machine; the act of creating fluid communication between the blood channel and the dialysate channel; and the act of passing dialysate through the dialysate channel and sending the blood in the blood channel into the patient's body.

[0055] In another embodiment, the method includes providing a hemodialysis system comprising a blood channel through which untreated blood is drawn from a patient's body and passed through a dialysis machine, and a dialysate channel through which dialysate flows from a dialysate supply unit through a dialysis machine; the act of fluidizing the blood channel and the dialysate channel; and the act of pushing gas into the dialysate channel to bring blood flow into the blood channel.

[0056] In yet another set of embodiments, this method is a method for performing hemodialysis. In one embodiment, the method includes providing a blood channel through which untreated blood can be drawn from a patient and passed through a dialysis machine; providing a dialysate channel through which dialysate can flow from a dialysate supply unit through a dialysis machine; providing raw materials to prepare a total volume of dialysate; providing water to be mixed with the dialysate raw materials; mixing a certain volume of water with a portion of the raw materials to prepare a first partial volume of dialysate, wherein the first partial volume is less than the total volume; pumping the partial volume of dialysate through the dialysate channel and through the dialysis machine; pumping blood through the blood channel and through the dialysis machine while the first partial volume of dialysate is being pumped to the dialysis machine; mixing a certain volume of water with a portion of the raw materials to prepare a second partial volume of dialysate; and storing the second partial volume of dialysate in a container while the blood and the first partial volume of dialysate are being pumped through the dialysis machine.

[0057] In another embodiment, the method includes passing blood and dialysate from a patient through a dialyzer contained within a hemodialysis system at a first velocity, and forming dialysate within the hemodialysis system at a second velocity substantially different from the first velocity, wherein excess dialysate is stored in a container contained within the hemodialysis system.

[0058] Another aspect of the present invention relates to a hemodialysis system comprising a dialysis unit and a user interface unit. The dialysis unit comprises an automated computer and dialysis equipment. The user interface unit comprises a user interface computer and a user interface, the user interface being adapted to display information and receive input. The automated computer is configured to receive requests for safety-sensitive information from the user interface computer and to access the safety-sensitive information on behalf of the user interface computer. The user interface computer is configured to display information related to the dialysis process via the user interface using the safety-sensitive information.

[0059] A further aspect of the present invention relates to a method for managing a user interface in a hemodialysis system. The method includes the steps of receiving inputs relating to the dialysis process in a user interface associated with a user interface computer, and, in response to the inputs, transmitting a request for safety-sensitive information from the user interface computer to an automated computer associated with the dialysis equipment. The method further includes the steps of accessing safety-sensitive information instead of the user interface, and using the safety-sensitive information to display information about the dialysis process via the user interface.

[0060] A further aspect of the present invention relates to a computer storage medium on which instructions for performing a method are encoded. The method includes receiving input relating to a dialysis process from a user interface associated with a user interface computer, and, in response to the input, transmitting a request for safety-sensitive information from the user interface computer to an automated computer associated with a dialysis machine. The method further includes accessing safety-sensitive information on behalf of the user interface computer, transmitting safety-sensitive information to the user interface computer, accessing screen design information stored in the user interface computer, and using the safety-sensitive information and screen design information to display information relating to the dialysis process on the user interface.

[0061] In another aspect, the present invention relates to one or more embodiments described herein, for example, a method for manufacturing a hemodialysis system. In yet another aspect, the present invention relates to one or more embodiments described herein, for example, a method for using a hemodialysis system.

[0062] In yet another aspect, the present invention relates to a control architecture for such a hemodialysis system, the control architecture comprising a user interface model layer, a treatment layer below the user interface model layer, and a machine layer below the treatment layer. The user interface model layer is configured to manage the state of a graphical user interface and to receive input from the graphical user interface. The treatment layer is configured to run a state machine that generates treatment commands based at least partially on input from the graphical user interface. The machine layer is configured to provide commands to actuators based on the treatment commands.

[0063] A further aspect of the present invention relates to a method for disinfecting a fluid path in a dialysis system. The method includes storing disinfection parameters, including a disinfection temperature and a disinfection time, in at least one storage medium. The method further includes circulating a fluid in a fluid path, monitoring the temperature of the fluid at each of a plurality of temperature sensors, and determining that disinfection of the fluid path is complete if the temperature of the fluid at each of the plurality of temperature sensors remains at or above the disinfection temperature for at least the disinfection time.

[0064] Another aspect of the present invention relates to at least one computer-readable medium on which instructions are encoded for a method of disinfecting a fluid path in a dialysis system when executed by at least one processing unit. The method includes the step of electronically receiving disinfection parameters, including a disinfection temperature and a disinfection time. The method further includes the steps of controlling a plurality of actuators to circulate a fluid in a fluid path, monitoring the temperature of the fluid at each of a plurality of temperature sensors, and determining whether the temperature of the fluid at each of the plurality of temperature sensors remains above the disinfection temperature for at least a disinfection time.

[0065] A further aspect of the present invention relates to a method for controlling the administration of an anticoagulant in a dialysis system. The method includes the steps of: storing an anticoagulant protocol containing a maximum dose of an anticoagulant in at least one storage medium; automatically administering an anticoagulant according to the anticoagulant protocol; and, after determining that the maximum dose of an anticoagulant has been administered, prohibiting the administration of any additional anticoagulant.

[0066] Another aspect of the present invention relates to at least one computer-readable medium encoded with instructions for a method of controlling the administration of an anticoagulant in a dialysis system when executed by at least one processing unit. The method includes the steps of: electronically receiving an anticoagulant protocol including a maximum dose of the anticoagulant; controlling a plurality of actuators to administer the anticoagulant according to the anticoagulant protocol; and, after determining that the maximum dose of the anticoagulant has been administered, prohibiting the administration of additional anticoagulants.

[0067] A further aspect of the present invention relates to a method for determining the fluid level in a dialysate tank of a dialysis system. The method includes the steps of tracking a first number of strokes that discharge fluid into the dialysate tank, tracking a second number of strokes that draw fluid out of the dialysate tank, and determining the fluid level in the dialysate tank, at least in part, based on the first number of strokes, the second number of strokes, and the volume per stroke.

[0068] A further aspect of the present invention relates to a method for determining the fluid level in a dialysate tank of a dialysis system. The method includes the steps of filling a reference chamber of known capacity to a predetermined pressure and evacuating the reference chamber into a dialysate tank. The method further includes the step of determining the pressure in the dialysate tank after evacuating the reference chamber into the dialysate tank. Furthermore, the method includes, at least in part, the step of determining the fluid level in the dialysate tank based on the determined pressure in the dialysate tank.

[0069] Another aspect of the present invention relates to a method for returning blood to a patient in the event of a power outage in a dialysis system that uses compressed air to operate a pump and / or valve during the dialysis process, wherein the dialysis system comprises a dialysis apparatus having a membrane that separates the blood flow path from the dialysate flow path. The method includes the step of identifying a power outage in the dialysis system. The method further includes the step of releasing compressed air from a reservoir associated with the dialysis system in response to the identification of the power outage. Furthermore, the method includes the step of using the released compressed air to increase the pressure in the dialysate flow path so that the blood in the blood flow path is returned to the patient.

[0070] A further aspect of the present invention relates to a method for returning extracorporeal blood to a patient using a compressed gas source in an extracorporeal treatment system during a power outage. The extracorporeal treatment system includes a filter having a semipermeable membrane that separates a blood flow path from an electrolyte flow path. The compressed gas is in communication with an electrolyte container via a valve, and the electrolyte container is in communication with an electrolyte flow path via a valve. The method includes the steps of: opening a first fluid flow path between the compressed gas and the electrolyte container to one or more electrically operated valves that control the dispersion of compressed gas or the dispersion of the electrolyte flow in the extracorporeal treatment system in response to a power cutoff to one or more electrically operated valves; opening a second fluid path between the electrolyte container and the filter to one or more electrically operated valves; closing an alternative fluid flow path to one or more third electrically operated valves when the alternative fluid path in the electrolyte flow path diverts the electrolyte from the filter; and using compressed gas to increase the pressure in the electrolyte flow path and return the blood in the blood flow path to the patient.

[0071] Another aspect of the present invention relates to a method for returning extracorporeal blood to a patient using a compressed gas source in an extracorporeal treatment system during a power outage. The extracorporeal treatment system includes a filter having a semipermeable membrane that separates a blood flow path from an electrolyte flow path. The compressed gas is in communication with an electrolyte container via a valve, and the electrolyte container is in communication with an electrolyte flow path via a valve. The method includes the steps of opening a fluid path between the compressed gas and the electrolyte container to one or more electrically operated valves that control the dispersion of compressed gas or the dispersion of the electrolyte flow in the extracorporeal treatment system in response to a power cut-off to one or more electrically operated valves, and using the compressed gas to induce an electrolyte flow from the electrolyte container through the filter, thereby returning blood in the blood flow path to the patient.

[0072] Other advantages and novel features of the present invention will become apparent from the following detailed description of various non-limiting embodiments of the invention, when considered together with the accompanying drawings. In the event that this specification and the references incorporated herein contain conflicting and / or inconsistent disclosures, this specification shall prevail. If two or more references incorporated herein contain conflicting and / or inconsistent disclosures with respect to each other, the later-published reference shall prevail.

[0073] Non-limiting embodiments of the present invention will be described by reference to the accompanying drawings, which are schematic and not intended to be drawn to an exact scale. In the drawings, each of the identical or substantially identical components shown is usually represented by a single reference numeral. For clarity, not all components are labeled in all drawings, and not all components of each embodiment of the present invention are shown where not an illustration is necessary for those skilled in the art to understand the invention. [Brief explanation of the drawing]

[0074] [Figure 1] This is a schematic diagram of a hemodialysis system. [Figure 2A] These are high-level schematic diagrams of various embodiments of a dialysis system. [Figure 2B] These are high-level schematic diagrams of various embodiments of a dialysis system. [Figure 3A] This is a schematic diagram showing an example of a fluid circuit diagram for a dialysis system. [Figure 3B] This is a schematic diagram showing an example of a fluid circuit diagram for a dialysis system. [Figure 4A] These are schematic diagrams of various embodiments of blood flow circuits that can be used in hemodialysis systems. [Figure 4B] These are schematic diagrams of various embodiments of blood flow circuits that can be used in hemodialysis systems. [Figure 4C] Figure 4A is a perspective view of the air trap shown. [Figure 4D]Figure 4A is a side view of the air trap shown. [Figure 5] This is a schematic diagram of one embodiment of a balance circuit that can be used in a hemodialysis system. [Figure 6] This is a schematic diagram of a directional circuit that can be used in a hemodialysis system. [Figure 7A] This is a schematic diagram of a mixing circuit that can be used in a hemodialysis system. [Figure 7B] This is a schematic diagram of a mixing circuit that can be used in a hemodialysis system. [Figure 8A] This is a graph showing the phase relationship. [Figure 8B] This is a graph showing the phase relationship. [Figure 8C] This is a graph showing the phase relationship. [Figure 9] This is a cross-sectional view of a valve that can be incorporated into an embodiment of a fluid control cassette. [Figure 10] This is a cross-sectional view of a pod pump that can be incorporated into an embodiment of a fluid control cassette. [Figure 11A] This is a schematic diagram of various pneumatic control systems for pod pumps. [Figure 11B] This is a schematic diagram of various pneumatic control systems for pod pumps. [Figure 12] This graph shows how the pressure applied to a pod pump can be controlled. [Figure 13A] This is a graph illustrating the detection of blockages. [Figure 13B] This is a graph illustrating the detection of blockages. [Figure 14] This is a diagram illustrating one embodiment of the control algorithm. [Figure 15] This is a diagram of one embodiment of a standard discrete PI regulator for a controller. [Figure 16] This is a schematic diagram of a dual-housing cassette configuration according to one embodiment. [Figure 17A] This is a schematic diagram of a part of the system priming in one embodiment of the present invention. [Figure 17B] This is a schematic diagram of a part of the system priming in one embodiment of the present invention. [Figure 17C] This is a schematic diagram of a part of the system priming in one embodiment of the present invention. [Figure 18A] In one embodiment of the present invention, the fluid flow of dialysate from the dialysate tank through the dialyzer and out of the drain is shown. [Figure 18B] In one embodiment of the present invention, the fluid flow of dialysate from the dialysate tank through the dialyzer and out of the drain is shown. [Figure 19] This demonstrates emptying the dialysate tank in another embodiment of the present invention. [Figure 20] This shows the final stage of a procedure using one embodiment of the present invention: purging the system with air. [Figure 21A] This shows the extraction of air from an anticoagulant pump in another embodiment of the present invention. [Figure 21B] This shows the extraction of air from an anticoagulant pump in another embodiment of the present invention. [Figure 21C] This shows the extraction of air from an anticoagulant pump in another embodiment of the present invention. [Figure 22A] This document demonstrates a integrity test according to several embodiments of the present invention. [Figure 22B] This document demonstrates a integrity test according to several embodiments of the present invention. [Figure 22C] This document demonstrates a integrity test according to several embodiments of the present invention. [Figure 22D] This document demonstrates a integrity test according to several embodiments of the present invention. [Figure 23] This shows a recirculation channel in another embodiment of the present invention. [Figure 24A] This describes priming of the system with dialysate in yet another embodiment of the present invention. [Figure 24B] This describes priming of the system with dialysate in yet another embodiment of the present invention. [Figure 24C]This describes priming of the system with dialysate in yet another embodiment of the present invention. [Figure 24D] This describes priming of the system with dialysate in yet another embodiment of the present invention. [Figure 25] This shows priming of an anticoagulant pump in yet another embodiment of the present invention. [Figure 26A] This shows the removal of dialysate from a blood flow circuit in one embodiment of the present invention. [Figure 26B] This shows the removal of dialysate from a blood flow circuit in one embodiment of the present invention. [Figure 26C] This shows the removal of dialysate from a blood flow circuit in one embodiment of the present invention. [Figure 26D] This shows the removal of dialysate from a blood flow circuit in one embodiment of the present invention. [Figure 26E] This shows the removal of dialysate from a blood flow circuit in one embodiment of the present invention. [Figure 26F] This shows the removal of dialysate from a blood flow circuit in one embodiment of the present invention. [Figure 27A] Another embodiment of the present invention shows the delivery of a bolus of an anticoagulant to a patient. [Figure 27B] Another embodiment of the present invention shows the delivery of a bolus of an anticoagulant to a patient. [Figure 27C] Another embodiment of the present invention shows the delivery of a bolus of an anticoagulant to a patient. [Figure 28] This shows solution injection in one embodiment of the present invention. [Figure 29A] This is a schematic diagram illustrating how emergency blood return procedures can be performed. [Figure 29B] This is a schematic diagram illustrating how emergency blood return procedures can be performed. [Figure 30A] This is an isometric view of the outer top plate of an exemplary embodiment of a cassette. [Figure 30B] This is a top view of the outer top plate of an exemplary embodiment of a cassette. [Figure 30C]This is an isometric view of the inner top plate of an exemplary embodiment of a cassette. [Figure 30D] This is a top view of the inner top plate of an exemplary embodiment of a cassette. [Figure 30E] This is a side view of the top plate of an exemplary embodiment of a cassette. [Figure 31A] This is an isometric view of the liquid side of the intermediate plate according to an exemplary embodiment of the cassette. [Figure 31B] This is a top view of the liquid side of the intermediate plate according to an exemplary embodiment of the cassette. [Figure 31C] This is an isometric view of the air side of the intermediate plate according to an exemplary embodiment of the cassette. [Figure 31D] This is a top view of the air-side intermediate plate according to an exemplary embodiment of the cassette. [Figure 32A] This is an isometric view of the inside of the bottom plate according to an exemplary embodiment of the cassette. [Figure 32B] This is an inside top view of the bottom plate according to an exemplary embodiment of the cassette. [Figure 32C] This is an isometric view of the outside of the bottom plate according to an exemplary embodiment of the cassette. [Figure 32D] This is an external top view of the bottom plate according to an exemplary embodiment of the cassette. [Figure 32E] This is a side view of the bottom plate according to an exemplary embodiment of a cassette. [Figure 33A] This is a top view of an exemplary assembled embodiment of a cassette with vials attached. [Figure 33B] This is a bottom view of an assembled exemplary embodiment of a cassette with vials attached. [Figure 33C] This is an exploded view of an assembled exemplary embodiment of a cassette containing vials. [Figure 33D] This is an exploded view of an assembled exemplary embodiment of a cassette containing vials. [Figure 34A] This is an isometric view of an exemplary embodiment of an intermediate plate of a cassette. [Figure 34B] This is an isometric top view of an intermediate plate in an exemplary embodiment of a cassette. [Figure 34C] This is an isometric view of an exemplary embodiment of a cassette intermediate plate. [Figure 34D] This is a side view of an exemplary embodiment of the intermediate plate of a cassette. [Figure 35A] This is an isometric view of an exemplary embodiment of the top plate of a cassette. [Figure 35B] This is a top view of an exemplary embodiment of the top plate of an exemplary embodiment of a cassette. [Figure 35C] This is an isometric view of an exemplary embodiment of the top plate of a cassette. [Figure 35D] This is an isometric view of an exemplary embodiment of the top plate of a cassette. [Figure 35E] This is a side view of an exemplary embodiment of the top plate of a cassette. [Figure 36A] This is an isometric bottom view of an exemplary embodiment of the bottom plate of a cassette. [Figure 36B] This is an isometric bottom view of an exemplary embodiment of the bottom plate of a cassette. [Figure 36C] This is an isometric top view of an exemplary embodiment of the bottom plate of a cassette. [Figure 36D] This is an isometric top view of an exemplary embodiment of the bottom plate of a cassette. [Figure 36E] This is a side view of an exemplary embodiment of the bottom plate of an exemplary embodiment of a cassette. [Figure 37] This is an isometric front view of an exemplary embodiment of the operating side of the intermediate plate of a cassette equipped with a valve, corresponding to Figure 36. [Figure 38A] This is a diagram illustrating an exemplary embodiment of the outer top plate of a cassette. [Figure 38B] This is a diagram illustrating an exemplary embodiment of the inner top plate of a cassette. [Figure 38C] This is a side view of an exemplary embodiment of the top plate of a cassette. [Figure 39A] This is a diagram illustrating an exemplary embodiment of the fluid side of the intermediate plate of a cassette. [Figure 39B] This is a front view of an exemplary embodiment of the air side of the intermediate plate of a cassette. [Figure 39C] This is a side view of an exemplary embodiment of the intermediate plate of a cassette. [Figure 40A] This is a diagram of an exemplary embodiment of the inside of the bottom plate of the cassette. [Figure 40B] This is a diagram of an exemplary embodiment of the outer surface of the bottom plate of the cassette. [Figure 40C] This is a side view of an exemplary embodiment of the intermediate plate of a cassette. [Figure 41A] This is an isometric view of an exemplary embodiment of the outer top plate of a cassette. [Figure 41B] This is a front view of an exemplary embodiment of the outer top plate of an exemplary embodiment of a cassette. [Figure 41C] This is an isometric view of an exemplary embodiment of the inner top plate of a cassette. [Figure 41D] This is a front view of an exemplary embodiment of the inner top plate of a cassette. [Figure 41E] This is a side view of the top plate of an exemplary embodiment of a cassette. [Figure 42A] This is an isometric view of an exemplary embodiment of the liquid side of the intermediate plate of a cassette. [Figure 42B] This is a front view of an exemplary embodiment of the liquid side of the intermediate plate of a cassette. [Figure 42C] This is an isometric view of an exemplary embodiment of the air side of the intermediate plate of a cassette. [Figure 42D] This is a front view of an exemplary embodiment of the air side of the intermediate plate of a cassette. [Figure 42E] This is a side view of an intermediate plate according to an exemplary embodiment of a cassette. [Figure 43A]This is an isometric view of the inside of the bottom plate according to an exemplary embodiment of the cassette. [Figure 43B] This is an inside front view of the bottom plate according to an exemplary embodiment of the cassette. [Figure 43C] This is an isometric view of an exemplary embodiment of the outside of the bottom plate of the cassette. [Figure 43D] This is a front view of an exemplary embodiment of the outside of the bottom plate of the cassette. [Figure 43E] This is a side view of the bottom plate according to an exemplary embodiment of a cassette. [Figure 44A] This is a top view of an exemplary assembled embodiment of a cassette. [Figure 44B] This is a bottom view of an exemplary embodiment of the cut and assembled parts. [Figure 44C] This is an exploded view of an exemplary assembled embodiment of a cassette. [Figure 44D] This is an exploded view of an exemplary assembled embodiment of a cassette. [Figure 45] This is a cross-sectional view of an exemplary embodiment of an assembled cassette. [Figure 46A] This is a front view of an exemplary assembled embodiment of a cassette system. [Figure 46B] This is an isometric view of an exemplary assembled embodiment of a cassette system. [Figure 46C] This is an isometric view of an exemplary assembled embodiment of a cassette system. [Figure 46D] This is an exploded view of an exemplary assembled embodiment of a cassette system. [Figure 46E] This is an exploded view of an exemplary assembled embodiment of a cassette system. [Figure 47A] This is an isometric view of an exemplary embodiment of a cassette system pod. [Figure 47B] This is an isometric view of an exemplary embodiment of a cassette system pod. [Figure 47C] This is a side view of an exemplary embodiment of a cassette system pod. [Figure 47D] This is an isometric view of an exemplary embodiment of one half of a cassette system pod. [Figure 47E] This is an isometric view of an exemplary embodiment of half of a cassette system pod. [Figure 48A] This is a diagram illustrating an exemplary embodiment of a cassette system pod membrane. [Figure 48B] This is a diagram illustrating an exemplary embodiment of a cassette system pod membrane. [Figure 49] This is an exploded view of an exemplary embodiment of a cassette system pod. [Figure 50A] This is an exploded view of one embodiment of a check valve fluid line in a cassette system. [Figure 50B] This is an exploded view of one embodiment of a check valve fluid line in a cassette system. [Figure 50C] This is an isometric view of one embodiment of a fluid line in a cassette system. [Figure 51A] This is one embodiment of a fluid flow circuit diagram for an integrated cassette system. [Figure 51B] This is one embodiment of a fluid flow circuit diagram for an integrated cassette system. [Figure 52A] These are various diagrams of one embodiment of a block that connects a pneumatic tube to a manifold, according to one embodiment of this system. [Figure 52B] These are various diagrams of one embodiment of a block that connects a pneumatic tube to a manifold, according to one embodiment of this system. [Figure 52C] These are various diagrams of one embodiment of a block that connects a pneumatic tube to a manifold, according to one embodiment of this system. [Figure 52D] These are various diagrams of one embodiment of a block that connects a pneumatic tube to a manifold, according to one embodiment of this system. [Figure 52E] These are various diagrams of one embodiment of a block that connects a pneumatic tube to a manifold, according to one embodiment of this system. [Figure 52F] These are various diagrams of one embodiment of a block that connects a pneumatic tube to a manifold, according to one embodiment of this system. [Figure 53] This is a diagram of another exemplary sensor manifold. [Figure 54] Figure 53 shows an example of a fluid path within a sensor manifold. [Figure 55] Figure 53 is a side view of an exemplary sensor manifold. [Figure 56A] This is a cross-sectional view of the exemplary sensor manifold shown in Figure 53, in section AA of Figure 56B. [Figure 56B] Figure 53 is a front view of an exemplary sensor manifold. [Figure 57] Figure 53 is an exploded view of an example sensor manifold. [Figure 58] Figure 53 shows an example of a sensor manifold with a printed circuit board and media edge connector. [Figure 59] This is an illustrative fluid circuit diagram of a hemodialysis system. [Figure 60] This is a perspective view of an exemplary embodiment of a user interface / treatment device combination. [Figure 61] Figure 60 is a schematic diagram of the exemplary hardware configurations of the dialysis unit and the user interface unit, respectively. [Figure 62] Figure 61 is a schematic diagram illustrating exemplary software processes that can be executed on the automated computer and user interface computer shown. [Figure 62A] This is a schematic diagram illustrating the interaction of the software processes described in relation to Figure 62. [Figure 62B] Figure 61 is a schematic diagram showing an alternative hardware configuration dialysis unit, including a hardware interface board with a field-programmable gate array (FPGA) safety system. [Figure 63]This is a schematic diagram illustrating the exemplary flow of information between hardware and software components of user interface computers and automation computers. [Figure 64] Figure 63 is a schematic diagram of an exemplary hierarchical state machine (HSM) that can be used by the UI controller shown. [Figure 65] Figure 61 is a schematic diagram of the normal screen display and alarm screen display that can be shown by the user interface shown. [Figure 66] This is a schematic diagram illustrating how the treatment layer interfaces with other layers, such as the machine layer and the user interface model layer. [Figure 67] Figure 66 is a schematic diagram showing an example implementation of the machine layer. [Figure 67A-1] This is a schematic diagram illustrating an exemplary implementation of impedance clearance operation in a dialysis machine. [Figure 67A-2] This is a continuation of Figure 67A-1. [Figure 67B] This is a schematic diagram illustrating an exemplary implementation of the dialysis fluid circulation operation. [Figure 67C] This is a schematic diagram illustrating an exemplary implementation of the heparin vial connection test operation. [Figure 67D] This is a schematic diagram illustrating an exemplary implementation of heparin bolus administration. [Figure 67E] This is a schematic diagram illustrating an example implementation of the tank discharge operation. [Figure 68-1] This is a schematic diagram illustrating an example implementation of a recirculation preparation application. [Figure 68-2] This is a continuation of Figure 68-1. [Figure 69A] This is a schematic diagram illustrating an example implementation of a blood tract cleaning application. [Figure 69B] This is a schematic diagram illustrating an example implementation of a blood tract cleaning application. [Figure 70A] This is a schematic diagram illustrating an example implementation of a disinfection application. [Figure 70B]This is a schematic diagram illustrating an example implementation of a disinfection application. [Figure 71] This is a schematic diagram illustrating an exemplary implementation of an endotoxin rinsing application. [Figure 72] This is a schematic diagram illustrating an example implementation of a treatment preparation application. [Figure 73A] This is a schematic diagram illustrating an example implementation of a patient connection application. [Figure 73B] This is a schematic diagram illustrating an example implementation of a patient connection application. [Figure 73C] This is a schematic diagram illustrating an example implementation of a patient connection application. [Figure 73D] This is a schematic diagram illustrating an example implementation of a patient connection application. [Figure 74A] This is a schematic diagram illustrating an example implementation of a dialysis application. [Figure 74B] This is a schematic diagram illustrating an example implementation of a dialysis application. [Figure 75A-1] This is a schematic diagram illustrating an example implementation of a solution injection application. [Figure 75A-2] This is a continuation of Figure 75A-1. [Figure 75B] This is a schematic diagram illustrating an example implementation of a solution injection application. [Figure 75C] This is a schematic diagram illustrating an example implementation of a solution injection application. [Figure 75D] This is a schematic diagram illustrating an example implementation of a solution injection application. [Figure 75E] This is a schematic diagram illustrating an example implementation of a solution injection application. [Figure 76A] This is a schematic diagram illustrating an example implementation of a blood return application. [Figure 76B-1] This is a schematic diagram illustrating an example implementation of a blood return application. [Figure 76B-2] This is a continuation of Figure 76B-1. [Figure 76C]A schematic diagram of the ultrafiltration fluid flow in one exemplary implementation of a hemodialysis machine is shown. [Figure 76D] A schematic diagram shows an ultrafiltration fluid flow, including periodic backflushing of the fluid across the dialysis membrane, in another exemplary implementation of a hemodialysis machine. [Figure 76E] A schematic diagram of the ultrafiltration fluid flow, including other fluid infusions or withdrawals from a patient undergoing hemodialysis, is shown. [Figure 76F] This shows a screen view displayed in a graphical user interface to summarize the results of hemodialysis therapy. [Figure 77] This is a schematic diagram illustrating an example implementation of a sample collection application. [Figure 78A] This is a schematic diagram illustrating an example implementation of a parts replacement application. [Figure 78B] This is a schematic diagram illustrating an example implementation of a parts replacement application. [Figure 78C] This is a schematic diagram illustrating an example implementation of a parts replacement application. [Figure 79A] This is a schematic diagram illustrating an example implementation of a chemical substance installation application. [Figure 79B] This is a schematic diagram illustrating an example implementation of a chemical substance installation application. [Figure 80] This diagram shows the pathway between the pressurized air tank and the dialysate tank in a hemodialysis system. [Figure 81] This is a fluid circuit diagram of a hemodialysis system showing the blood-side flow path and the dialysate-side flow path used to measure the clearance of a dialysis machine according to an embodiment of the present invention. [Figure 82] This is a plot of measured model conductivity data versus pump stroke count used to determine dialysis machine clearance according to an embodiment of the present invention. [Figure 83] Figure 82 shows a plot correlating the dialysis machine parameter K, obtained from data such as those shown, with the measured urea clearance. [Figure 84]A schematic diagram of the equilibrium circuit, including the equilibrium chamber and associated blood leak sensors, is shown. [Figure 85] A front cross-sectional view of the equilibrium chamber and blood leak sensor in an exemplary embodiment is shown. [Figure 86] Figure 85 shows a bottom view of the embodiment. [Figure 87] Figure 85 shows a left-lower perspective view of the embodiment. [Figure 88] A perspective view of the blood leak sensor bracket in this exemplary embodiment is shown. [Figure 89] A schematic diagram of a dialysis system including an air trap and accumulator in a water supply conduit in an exemplary embodiment is shown. [Figure 90] A front view of an air trap in an exemplary embodiment is shown. [Figure 91] Figure 90 shows a bottom view of the air trap. [Figure 92] Figure 90 shows a front cross-sectional view of the air trap. [Figure 93] A front view of the accumulator in an exemplary embodiment is shown. [Figure 94] Figure 93 shows a bottom view of the accumulator. [Figure 95] Figure 93 shows a front cross-sectional view of the air trap. [Figure 96] Figure 93 shows a front perspective view of the air trap, specifically the upper left section. [Figure 97] A top view of a cassette system in an exemplary embodiment is shown. [Figure 98] Figure 97 shows a rear view of the cassette system. [Figure 99] Figure 97 shows the right side view of the cassette system. [Figure 100] Figure 97 shows a perspective view of the upper right rear of the cassette system. [Figure 101A] This is an isometric view showing the front of a pressure distribution module according to an embodiment of the present invention. [Figure 101B] This is an isometric view showing the rear view of a pressure distribution module according to an embodiment of the present invention. [Figure 102]Figure 101 is an isometric view of the pressure distribution module and the left and right interface blocks used with it. [Figure 103] Figure 101 is an exploded view showing how the interface block is fixed to the pressure distribution module. [Figure 104] This is a detailed isometric view of the rear of a pressure distribution module according to an embodiment of the present invention. [Figure 105] This is an exploded view of an assembly of a multi-component pneumatic manifold. [Figure 106] This is an isometric view showing the flow path of the end manifold block. [Figure 107] This is an exploded view of an alternative embodiment of a multi-component pneumatic manifold. [Figure 108] This is an exploded view of an alternative embodiment of a multi-component pneumatic manifold. [Figure 109] This is an isometric view of a pressure distribution module showing the variable valve and pressure sensor PCB. [Figure 110] This is an isometric view of a pressure distribution module showing cartridge valves and pressure supply fittings. [Figure 111A] This is an isometric view showing the details of the intermediate manifold block. [Figure 111B] This is an isometric view showing the details of the intermediate manifold block. [Figure 111C] This is an isometric view showing the details of the intermediate manifold block. [Figure 111D] This is an isometric view showing the details of the intermediate manifold block. [Figure 112] This is a schematic diagram of an exemplary pod pump equipped with an FMS system. [Figure 113] This is a schematic diagram of the air pressure path configuration for the blood cassette. [Figure 114] This is a schematic diagram of the air pressure path configuration for the internal dialysate cassette. [Figure 115] This is a schematic diagram of the air pressure path configuration for an external dialysis fluid cassette. [Figure 116] This is a schematic diagram of the air pressure path setting for a mixed cassette. [Figure 117] This is a schematic diagram of the pneumatic path configuration for the occluder. [Figure 118] This is a flow circuit diagram for a blood cassette. [Figure 119] This is a flow circuit diagram for an internal dialysate cassette. [Figure 120] This is a flow circuit diagram for an external dialysate cassette. [Figure 121] This is a schematic diagram for a mixed cassette system. [Figure 122] This is a schematic diagram of a directional circuit that can be used in a hemodialysis system. [Figure 123A] This is a schematic diagram of the heater temperature control loop. [Figure 123B] This is a schematic diagram of a heater temperature control loop nested inside a fluid temperature control loop. [Figure 123C] This is a schematic diagram of the heater power control loop. [Figure 124] A flowchart illustrating a method of communication between a tablet and a base according to an embodiment of this disclosure is shown. [Figure 125] A flowchart illustrating a method of communication between a tablet and a base according to an embodiment of this disclosure is shown. [Figure 126] A flowchart illustrating a method of communication between a tablet and a base according to an embodiment of this disclosure is shown. [Figure 127] A flowchart illustrating a method of communication between a tablet and a base according to an embodiment of this disclosure is shown. [Figure 128] A flowchart illustrating a method of communication between a tablet and a base according to an embodiment of this disclosure is shown. [Figure 129] A flowchart illustrating a method of communication between a tablet and a base according to an embodiment of this disclosure is shown. [Figure 130] This is a plot of simulated valve commands and pressure responses used in cross-correlation calculations. [Figure 131] This is a plot of an exemplary curve from a cross-correlation calculation. [Figure 132] This is a plot of the simulated valve command and pressure response as the phase angle between the command and pressure changes. [Figure 133] This is a plot of cross-correlation results based on simulated valve commands and responses, including phase shifts. [Figure 134] This is a plot of pressure and cross-correlation from the filling and dispensing strokes. [Figure 135] This is a plot of pressure and cross-correlation from filling and discharging strokes with blockage. [Figure 136] This is a schematic diagram of a pressure-driven diaphragm pump driven by a binary valve. [Figure 137] This is a plot of valve operation and resulting pump pressure during the discharge stroke. [Figure 138] This is a plot of the pump pressure and integrated pressure change while the valve is closed relative to the discharge stroke. [Figure 139] This is a plot of the pump pressure and integrated pressure change while the valve is closed relative to the filling stroke. [Figure 140] This is a schematic diagram of a pressure-driven diaphragm pump driven by a binary valve. [Figure 141] This is a cross-section diagram of a water inlet module used in a hemodialysis machine. [Figure 142] Figure 141 is a perspective view of the water inlet module. [Figure 143] Figure 141 shows the water sensor used in the water inlet module. [Figure 144] Figure 1 shows the location of the water inlet module in a hemodialysis machine. [Figure 145A] This diagram shows the operation of a dialysis machine when used with a tablet having a user interface for a dialysis machine according to an embodiment of the disclosure. [Figure 145B] This diagram shows the operation of a dialysis machine when used with a tablet having a user interface for a dialysis machine according to an embodiment of the disclosure. [Figure 146A] An exemplary pump cassette is shown. [Figure 146B] An exemplary pump cassette is shown, representing a cross-sectional view of the pump cassette along the line shown in Figure 146A. [Figure 147A] An exemplary pump bulkhead is shown. [Figure 147B] An exemplary pump bulkhead is shown. [Figure 147C] An exemplary pump bulkhead is shown. [Figure 147D] An exemplary pump bulkhead is shown. [Figure 148A] The diagram shows a different pump bulkhead with a raised feature or bump on the pumping chamber side of the bulkhead. [Figure 148B] The diagram shows a different pump bulkhead with a raised feature or bump on the pumping chamber side of the bulkhead. [Figure 149A] Further figures of the pump bulkhead, showing raised features or bumps on the bulkhead body, are shown. [Figure 149B] Further diagrams of the pump bulkhead show raised features or bumps on the bulkhead body, and Figure 146B shows a cross-sectional view of the bulkhead along the line shown in Figure 146A. [Figure 150] This diagram shows a cross-sectional view of a diaphragm pump in which a partition wall is located within the pump's pumping chamber. [Figure 151] Figure 150 shows an enlarged cross-sectional view of the area surrounding the pump's bulkhead. [Figure 152A] An alternative embodiment of the pump bulkhead is shown. [Figure 152B] An alternative embodiment of the pump bulkhead is shown, and Figure 152B represents a cross-sectional view of the bulkhead along the line shown in Figure 152A. [Figure 153] This diagram shows a cross-sectional view of a diaphragm pump, with a partition wall located inside the pump's control chamber. [Figure 154] Figure 153 shows an enlarged cross-sectional view of the area surrounding the pump's bulkhead. [Figure 155] This is an exemplary plot of a dual heater configuration where two heater elements are controlled by a 25% duty cycle. [Figure 156]This example demonstrates pump control chamber pressure tracking during a pump filling stroke and flow-referenced calculation of the applied and measured pressure signals. [Figure 157A] This example demonstrates pump control chamber pressure tracking, flow metric calculation, and pump control operation during a period of gradual blockage of the flow line connected to the pump inlet. [Figure 157B] This example demonstrates pump control chamber pressure tracking, flow metric calculation, and pump control operation during a period of gradual blockage of the flow line connected to the pump inlet. [Modes for carrying out the invention]

[0075] The present invention relates to hemodialysis systems and similar extracorporeal blood treatment systems, including various systems and methods for making hemodialysis more efficient, easier, and / or less expensive. One aspect of the present invention generally relates to novel fluid circuits for fluid flow. In one set of embodiments, the hemodialysis system may include blood flow channels and dialysate flow channels, the dialysate flow channels including one or more of a balancing circuit, a mixing circuit, and / or a directional circuit. In some cases, the preparation of dialysate by the mixing circuit can be separated from the patient's dialysis. In some cases, the circuits are defined at least partially within one or more cassettes and optionally interconnected with conduits, pumps, etc. In one embodiment, the fluid circuits and / or various fluid flow channels can be at least partially spatially and / or thermally isolated from the electrical components of the hemodialysis system. In some cases, a gas supply unit can be provided that is in fluid communication with the dialysate flow channels and / or the dialysis machine, which, when driven, can facilitate the flow of dialysate through the dialysis machine and facilitate the return of blood in the blood flow channels to the patient. Such systems may be useful, for example, in some emergency situations (e.g., power outages) where it is desirable to return as much blood as possible to the patient. In another aspect of the present invention, the hemodialysis system may also include one or more fluid processing devices, such as pumps, valves, and mixers, which can be operated using a control fluid, such as air. In some cases, the control fluid may be discharged to the fluid processing device using an external pump or other device, which may be detachable. In one embodiment, one or more of the fluid processing devices may be generally rigid (e.g., having a spheroidal shape), and optionally, a partition wall dividing the device into a first and second compartment is housed within the device.

[0076] Various aspects of the present invention relate to novel systems for hemodialysis, such as hemofiltration systems, hemodialysis filtration systems, and plasma exchange systems. Therefore, although the various systems and methods described herein are described in relation to hemodialysis, they are applicable to other dialysis systems and / or any extracorporeal settings capable of treating other bodily fluids such as blood or plasma.

[0077] As described above, a hemodialysis system typically includes blood channels and dialysate channels. It should be noted that within these channels, the fluid flow is not necessarily linear, and there can be any number of “branchings” within the channel through which the fluid can flow from the inlet to the outlet. Examples of such branchings will be discussed in detail later. In the blood channel, blood is drawn from the patient, passed through the dialysis machine, and then returned to the patient. The blood is processed by the dialysis machine, and waste molecules (e.g., urea, creatinine, etc.) and water are transferred from the blood through the translucent membrane of the dialysis machine into the dialysate that passes through the dialysis machine via the dialysate channel. In various embodiments, blood can be drawn from the patient through two lines (e.g., an arterial line and a venous line, i.e., a “double needle” flow), or, in some cases, blood can be drawn from and returned to the patient through the same needle (e.g., two lines can coexist within the same needle, i.e., a “single needle” flow). In further embodiments, a "Y"-shaped or "T"-shaped section is used, where blood is drawn from and returned to the patient through a single patient connection with two branches (one for the drawn blood and the second for the blood return). In embodiments, the "Y"-shaped or "T"-shaped connection can be formed with a single-lumen needle or catheter. In another embodiment, a "double-needle" flow effect can be obtained by using a single catheter or needle having two lumens. The patient can be any subject requiring hemodialysis or a similar procedure, but is typically human. However, hemodialysis can be performed on non-human subjects such as dogs, cats, and monkeys.

[0078] In the dialysate flow path, fresh dialysate is prepared and passed through the dialyzer to treat blood from the blood flow path. The dialysate can also be equilibrated within the dialyzer for blood treatment (i.e., the pressure between the dialysate and the blood is equalized), meaning that the pressure of the dialysate passing through the dialyzer matches, often precisely, or in some embodiments, within a range of at least 1% or 2% of the blood pressure, the pressure of the dialysate passing through the dialyzer. In some cases, it may be desirable to maintain a larger pressure difference (either positive or negative) between the blood flow path and the dialysate flow path. After passing through the dialyzer, the used dialysate, containing waste molecules (described later), is disposed of in some way. In some cases, the dialysate is heated using a suitable heater, such as an electric resistance heater, before blood treatment within the dialyzer. The dialysate can also be filtered using an ultrafiltration device to remove, for example, contaminants, infectious microorganisms, and residues. The ultrafiltration device may have a mesh or pore size selected to prevent these species from passing through. For example, the mesh or pore size may 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. Using dialysate, waste molecules (e.g., urea, creatinine, potassium ions, phosphates, etc.) and water are drawn into the dialysate from the blood by osmosis or convection, and the dialysate is well known to those skilled in the art.

[0079] Dialysis fluid typically contains various ions, such as sodium chloride, bicarbonate, potassium, and calcium, at concentrations similar to those found in normal blood. In some cases, the concentration of bicarbonate may be somewhat higher than that found in normal blood. Dialysis fluid is usually prepared by mixing one or more raw materials, namely "acid" (which can include various types such as acetic acid, glucose, NaCl, CaCl, KCl, MgCl, etc.), sodium bicarbonate (NaHCO3), and / or sodium chloride (NaCl), with water from a water supply. The preparation of dialysis fluid, including the use of appropriate concentrations of salt, osmolality, pH, etc., is well known to those skilled in the art. As will be described in detail later, dialysis fluid does not need to be prepared in the same proportions as the dialysis fluid used to treat blood. For example, dialysis fluid can be prepared simultaneously with or before dialysis and stored in a dialysis fluid storage container, etc.

[0080] In a dialysis machine, dialysate and blood are typically separated by a semipermeable membrane, preventing physical contact between them. These semipermeable membranes are usually formed from polymers such as cellulose, polyaryl ethersulfone, polyamide, polyvinylpyrrolidone, polycarbonate, and polyacrylonitrile. These polymers allow the transport of ions or small molecules (e.g., urea, water), but not the transport or convection of clots during blood treatment. In some cases, even larger particles, such as beta-2-microglobulin, can pass through the membrane. In other cases, convective transport of fluids, ions, and small molecules may occur, for example, if there is a static pressure difference across the semipermeable membrane.

[0081] Dialysis fluid and blood do not come into contact with each other within the dialysis machine, and are usually separated by a membrane. Often, dialysis machines are configured according to a "shell and tube" design, in which multiple individual tubes or fibers (through which blood flows) formed from a semipermeable membrane are surrounded (or sometimes reversed) by a larger "shell" through which the dialysis fluid flows. The flow of dialysis fluid and blood through the dialysis machine may, in some cases, be reverse or parallel. Dialysis machines are well known to those skilled in the art and are available from a number of different commercial sources.

[0082] In one embodiment, the dialysate flow path can be divided into one or more circuits, such as an equilibrium circuit, a mixing circuit, and / or a directional circuit. It should be noted that the circuits do not necessarily need to be fluidically isolated from the fluid flow; that is, the fluid can flow in and out of the fluid circuits. Similarly, the fluid can move from one fluid circuit to another if the fluid circuits are in fluid communication or fluidly connected to each other. It should be noted that the term "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 dialysate.

[0083] A fluid circuit is typically a distinct module that accepts a certain number of fluid inputs and, in some cases, performs one or more operations on the fluid inputs before directing the fluid to a suitable output. In some embodiments of the present invention, as will be described later, the fluid circuit is defined as a cassette. As a specific example, a dialysate flow path may include an equilibrium circuit, a directionation circuit, and a mixing circuit. As another example, a blood flow path may include a blood flow circuit. In the equilibrium circuit, dialysate is introduced into the circuit, and a pump acts on the dialysate so that the pressure of the dialysate passing through the dialyzer is in equilibrium with the pressure of the blood passing through the dialyzer, as described above. Similarly, in the directionation circuit, fresh dialysate is passed from the mixing circuit to the equilibrium circuit, and used dialysate is passed from the equilibrium circuit to the drain. In the mixing circuit, the raw materials and water are mixed to form fresh dialysate. The blood flow circuit is used to draw blood from the patient, pass the blood through the dialyzer, and return the blood to the patient. These circuits will be described in detail later.

[0084] Figure 2A schematically shows an example of a hemodialysis system having such fluid circuits as a high-level schematic diagram. Figure 2A shows a dialysis system 5 including a blood flow circuit 10, through which blood flows from the patient to the dialysis machine 14, and treated blood is returned to the patient. The hemodialysis system in this example also includes an equilibrium circuit 143 (part of the inner or internal dialysate circuit), which takes the dialysate after it has passed through the ultrafiltration device 73, passes the dialysate through the dialysis machine 14, and the used dialysate returns from the dialysis machine 14 to the equilibrium circuit 143. A directional circuit 142 (part of the outer or internal dialysate circuit) processes the fresh dialysate before it passes through the ultrafiltration device 73. A mixing circuit 25 prepares the dialysate with various raw materials 49 and water, for example, during and / or prior to dialysis, as needed. The directional circuit 142 can also receive water from the water supply unit and pass it to the mixing circuit 25 to prepare the dialysate, and the directional circuit 142 can also receive used dialysate from the equilibrium circuit 143 and remove it from the system 5 as waste via the drain 31. A conduit 67, also shown by a dotted line, can be connected between the blood flow circuit 10 and the directional circuit 142, for example, to disinfect the hemodialysis system. In one set of embodiments, one or more of these circuits (e.g., the blood flow circuit, equilibrium circuit, directional circuit, and / or mixing circuit) may include a cassette, which incorporates the valves and pumps necessary to control the flow through its portion. Examples of such systems will be described in detail later.

[0085] Figure 2B is a schematic diagram of a hemodialysis system according to an embodiment of the present invention. In this schematic diagram, a blood flow cassette 22 is used to control the flow through a blood flow circuit 10, and a dialysate cassette 21 is used to control the flow through a dialysate circuit. The blood flow cassette includes an anticoagulant valve or pump 12 to control the flow of anticoagulant into the blood, and a blood flow pump 13 which may optionally include a pair of pod pumps, along with at least one inlet valve 24 (in other embodiments, two or more inlet valves are included) to control the flow of blood through the cassette 22. These pod pumps may be of the type (or a variation thereof) described in U.S. Provisional Patent Application No. 60 / 792,073, filed April 14, 2006, entitled "Extracorporeal Thermal Therapy Systems and Methods," or in U.S. Patent Application No. 11 / 787,212, filed April 13, 2007, entitled "Fluid Pumping Systems, Devices and Methods," each of which is incorporated herein by reference as a whole. All pumps and valves in this example can be controlled by a control system, such as an electronic and digital control system, although other control systems may be possible in other embodiments.

[0086] By providing two pod pumps, blood can be flowed more continuously through the blood flow circuit 10; however, in other embodiments, a single pod pump, such as a single pod pump, can be used. The pod pump may include active inlet and outlet valves (instead of passive check valves at the inlet and outlet), thereby allowing the flow in the blood flow circuit 10 to be reversed under certain conditions. For example, by reversing the flow within the blood flow circuit, the hemodialysis system can verify whether the outlet of the blood flow circuit is properly connected to the patient and thereby whether the treated blood is being returned correctly to the patient. For example, if the patient connection point becomes detached due to a fall or other reason, reversing the blood flow pump will draw in air instead of blood. This air can be detected by a standard air detector incorporated into the system.

[0087] In another embodiment, a blood outlet valve 26 and an air trap / filter 19 located downstream of the dialysis machine can be incorporated into the blood flow cassette 22. The pod pump and all valves of the blood flow cassette 22 (including valves relating to the inlet and outlet of the pod pump) can be pneumatically actuated. In one embodiment, the positive and negative gas pressure sources are provided by a base unit holding the cassette or another device holding the cassette. However, in other embodiments, the positive and negative gas pressures can be provided by an external device fluid-connected to the cassette, or by any device incorporated into the system. The pump chamber can be operated as described in U.S. Provisional Patent Application No. 60 / 792,073, filed April 14, 2006, entitled "Extracorporeal Thermal Therapy Systems and Methods," or in U.S. Patent Application No. 11 / 787,212, filed April 13, 2007, entitled "Fluid Pumping Systems, Devices and Methods." For example, the pump can be controlled to detect the end of a stroke, as described later. The blood flow cassette 22 may also include integrally formed spikes for receiving a vial of anticoagulant.

[0088] In one embodiment, the anticoagulant pump includes three fluid valves (which can be controlled by a control fluid) and a single pumping compartment (however, in other embodiments, there may be two or more pumping compartments). The valves can connect the compartment to a filtered air vent, to an anticoagulant vial (or other anticoagulant supply unit such as a bag or bottle), or to a blood flow path. The anticoagulant pump can be operated by sequentially opening and closing the fluid valves and controlling the pressure in the pump compartment, for example, via a control fluid. When the anticoagulant is removed from the vial, it is replaced by an equal volume of air, for example, via The pressure inside the vial can be kept relatively constant. Replacing the anticoagulant volume with air in this way can be done, for example, by (i) opening a valve from a filtered air vent to the pump compartment, (ii) drawing air into the compartment by connecting a negative pressure source to the chamber, (iii) closing the air vent valve, (iv) opening the valve connecting the compartment to the vial, and (v) connecting a positive pressure source to the compartment, thereby forcing air into the vial. The anticoagulant can be delivered from the vial into the bloodstream using a similar procedure, but with valves to the vial and the bloodstream instead of valves to the air vent and vial.

[0089] Figure 3A is a schematic diagram showing a specific embodiment of the overall overview shown in Figure 2A. Figure 3A details how, according to one embodiment of the present invention, the blood flow circuit 141, the balancing circuit 143, the direction circuit 142, and the mixing circuit 25 can be implemented in the cassette and correlated with each other and with the dialysis machine 14, the ultrafiltration machine 73, and / or the heater 72. Naturally, Figure 3A is just one possible embodiment of the overall hemodialysis system of Figure 2A, and it should be understood that other fluid circuits, modules, flow paths, arrangements, etc., are possible in other embodiments. Examples of such systems will be described in detail later and can be found in the following literature, each incorporated herein by reference. Specifically, U.S. Provisional Patent Application No. 60 / 903,582, titled "Hemodialysis System and Methods," filed on February 27, 2007; U.S. Provisional Patent Application No. 60 / 904,024, titled "Hemodialysis System and Methods," filed on February 27, 2007; U.S. Patent Application No. 11 / 871,680, titled "Pumping Cassette," filed on October 12, 2007; U.S. Patent Application No. 11 / 871,712, titled "Pumping Cassette," filed on October 12, 2007; U.S. Patent Application No. 11 / 871,712, titled "Pumping Cassette," filed on October 12, 2007. These include U.S. Patent Application No. 11 / 871,787, titled "Cassette"), U.S. Patent Application No. 11 / 871,793, filed on October 12, 2007, titled "Pumping Cassette", or U.S. Patent Application No. 11 / 871,803, filed on October 12, 2007, titled "Cassette System Integrated Apparatus".

[0090] The components of Figure 3A will be described in detail later. Briefly, the blood flow circuit 141 includes an anticoagulant supply unit 11 and a blood flow pump 13 that delivers blood from the patient to the dialysis machine 14. The anticoagulant supply unit 11 is shown as being in the path of blood flowing toward the dialysis machine, but in other embodiments, it may instead be located in the path of blood flowing toward the patient, or in another preferred location, such as upstream or downstream of the blood flow pump 13. The anticoagulant supply unit 11 may be located at any position downstream from the blood flow pump 13. The equilibrium circuit 143 includes two dialysate pumps 15 and a bypass pump 35 that similarly deliver dialysate to the dialysis machine 14. The direction circuit 142 includes a dialysate pump 159 that delivers dialysate from the dialysate tank 169 through the heater 72 and / or ultrafiltration device 73 to the equilibrium circuit. The direction circuit 142 also takes waste fluid from the equilibrium circuit 143 and directs it to the drain 31. In some cases, as will be described later, the blood flow circuit 141 can be connected to the directional circuit 142 via the conduit 67, for example, for disinfection. The dialysate flows from the dialysate supply unit into the dialysate tank 169.

[0091] In some embodiments, the present invention provides a method for preparing dialysate from water contained in or supplied to a system and at least one supply solute contained in or supplied to a system. For example, as shown in Figures 3A, 3B, 7A, and 7B, dialysate is produced in a mixing circuit 25. Water from the water supply unit 30 flows into the mixing circuit 25 through a directional circuit 142. Dialysate raw materials 49 (e.g., bicarbonate and acid) are also added to the mixing circuit 25, and dialysate is produced using a series of mixing pumps 180, 183, and 184, after which the dialysate is sent to the directional circuit 142. The above method and control for ensuring that acceptable dialysate quality is produced and maintained during treatment will be described in more detail later.

[0092] In this example system, one of the fluid circuits is a blood flow circuit, for example, the blood flow circuit 141 in FIG. 3A. In the blood flow circuit, blood from the patient is pumped through the dialysis device and then returned to the patient. In some cases, the blood flow circuit is incorporated into a cassette as described below, but this is not necessarily required. The flow of blood through the blood flow circuit may, in some cases, be balanced with the flow of dialysis fluid through the dialysis fluid flow path, particularly through the dialysis device and the equilibrium circuit.

[0093] FIG. 4A shows an example of a blood flow circuit. Generally, blood flows from the patient through the arterial line 203 through the blood pump 13 to the dialysis device 14 (the direction of the normal dialysis flow is indicated by the arrow 205, but in some modes of operation, as described below, the flow can be in a different direction). Optionally, an anticoagulant can be introduced into the blood from the anticoagulant supply through the anticoagulant pump 80. As shown in FIG. 4A, the anticoagulant can enter the blood flow path after the blood has passed through the blood pump 13, but in other embodiments, the anticoagulant can be added at any suitable position along the blood flow path. For example, in FIG. 4B, the anticoagulant enters the blood flow path before the blood passes through the blood pump 13. This can be useful, for example, when a blood pump cassette of the type shown in FIGS. 30C - 33D is used and the blood flow is directed to enter the cassette at the top and exit at the bottom. Thus, the blood pump chamber can also serve to trap air that may be present in the blood before it is fed into the dialysis device. In other embodiments, the anticoagulant supply 11 can be placed anywhere downstream of the blood pump. After passing through the dialysis device 14 and undergoing dialysis, the blood optionally passes through an air trap and / or a blood sample port 19 and returns to the patient through the venous line 204.

[0094] As shown in Figure 4A, the blood flow cassette 141 also includes one or more blood flow pumps 13 that move blood through the blood flow cassette. The pumps may be pumps driven by a control fluid, such as those described later. For example, in one embodiment, the pumps 13 may comprise two (or more) pod pumps, for example, the pod pump 23 in Figure 4A. Each pod pump may include a rigid chamber in this particular example, which has a flexible partition or membrane that divides each chamber into a fluid compartment and a control compartment. These compartments have four inlet / outlet valves, two in the fluid compartment and two in the control compartment. The valves in the control compartments of the chamber may be bidirectional proportional valves, one connected to a first control fluid source (e.g., a high-pressure air source) and the other connected to a second control fluid source (e.g., a low-pressure air source) or a vacuum sink. The fluid valves in the compartments can be opened and closed to direct the fluid flow when the pod pumps are pumping. Non-limiting examples of pod pumps are described in U.S. Provisional Patent Application No. 60 / 792,073, filed April 14, 2006, entitled "Extracorporeal Thermal Therapy Systems and Method," and U.S. Patent Application No. 11 / 787,212, filed April 13, 2007, entitled "Fluid Pumping Systems, Devices and Methods," each incorporated herein by reference. Further details of pod pumps are provided below. When two or more pod pumps are present, they may be operated in any preferred manner, for example, synchronously, asynchronously, in phase, or out of phase.

[0095] For example, in some embodiments, the two-pump type pump can be circulated with a phase shift so as to affect the pumping cycle. For example, while one pump chamber is being filled, the second pump chamber is emptied. To provide any desired pumping cycle, a phase relationship between 0° (the pod pumps act in the same direction and are filled and emptied simultaneously) and 180° (the pod pumps act in opposite directions and one pod pump is filled while the other pump is empty) can be selected.

[0096] A 180° phase relationship can provide a continuous flow through the pod pump cassette. This can be useful, for example, when used with, for example, a double-lumen flow or a "Y" or "T" connection. However, setting a 0° phase relationship can be useful in some cases, such as in the case of a single-lumen flow, in situations where a "Y" or "T" connection is made by a single needle or single-lumen catheter, or in other cases. In the 0° relationship, the pod pump is first filled from the needle and then the same needle is used to return the blood to the patient through the blood flow path. Further, in some cases, operation at a phase between 0° and 180° can be used to achieve a push / pull relationship (hemofiltration or continuous backflush) across the dialysis device. FIGS. 8A-8C are graphical diagrams of examples of such phase relationships. In these figures, the volume or flow of each pod pump, the volume of each pod pump and the total hold-up volume of both pod pumps are shown as a function of time. These times and flow rates are arbitrarily selected and are presented here to show the relationships between the pod pumps at different phases. For example, in the 180° phase relationship (FIG. 8B), the total hold-up volume remains substantially constant.

[0097] In some cases, as shown in Figure 14, an anticoagulant (e.g., heparin, or any other anticoagulant known to those skilled in the art) can be mixed with the blood in the blood flow cassette 141. For example, the anticoagulant can be contained in a vial 11 (or other anticoagulant supply unit such as a tube or bag), and the blood flow cassette 141 can receive the anticoagulant vial by an integrally formed spike 201 (in one embodiment, a needle) that can puncture the seal of the vial. The spike can be formed from plastic, stainless steel, or another suitable material, and in some cases, it can be made of a sterilizable material, for example, the material can withstand temperatures and / or radiation high enough to sterilize the material. As an example, as shown in Figure 4A, the blood flow cassette 141 and the spike 201 can be integrally formed, and the vial 11 can be placed on the spike to puncture the seal of the vial, thereby allowing the anticoagulant to flow into the blood flow cassette and mix with the blood in the blood flow channel, or in some cases, with the dialysate as described later.

[0098] The flow of anticoagulant into the blood in the blood flow cassette 141 can be controlled using a third pump 80, which may also act as a metering chamber. The third pump 80 may or may not be of the same design as pump 13. For example, the third pump 80 may be a pod pump and / or it may be operated by a control fluid such as air. For example, the third pump 80 may be a membrane-based metering pump or a partition-based metering pump. For example, as shown in Figure 4A, the third pump 80 may include a rigid chamber which has a flexible partition dividing the chamber into a fluid compartment and a control compartment. The valve of the control compartment of the chamber may be connected to a first control fluid source (e.g., a high-pressure air source), and the other compartment may be connected to a second control fluid source (e.g., a low-pressure air source) or a vacuum sink. The valve of the fluid compartment of the chamber can be opened and closed according to the control compartment, and thus the flow of anticoagulant into the blood is controlled. Further details of such pod pumps will be described later. In one embodiment, as will be described later, it is also possible to introduce air into the blood flow path through the filter 81.

[0099] Fluid Management System ("FMS") measurements can be used to measure the volume of fluid being pumped through a pump chamber during a membrane or partition stroke, or to detect air in the pumping chamber. FMS methods are described in U.S. Patents 4,808,161, 4,826,482, 4,976,162, 5,088,515, and 5,350,357, which are incorporated herein by reference as a whole. In some cases, the volume of fluid discharged by an anticoagulant pump, dialysate pump, or other membrane-based pump is determined using an FMS algorithm, where volume measurements at the end of the filling stroke and the end of the discharging stroke are calculated using changes in chamber pressure. The difference between the calculated volumes at the end of the filling stroke and the end of the discharging stroke is the actual stroke volume. This actual stroke volume can be compared to the predicted stroke volume for a chamber of a particular size. If the actual and predicted volumes differ significantly, the stroke is not properly completed, and an error message may be generated.

[0100] If stroke capacity is collected by a scale, calculations can be performed in reverse to determine the calibration value relative to the reference chamber. The FMS system can be exhausted to the atmosphere for FMS measurements. Alternatively, the system can be exhausted to a positive high-pressure source and a negative low-pressure source for FMS measurements. Doing so offers the following advantages in particular: (1) If the high-pressure source is a pressure reservoir with controlled pressure, there is an opportunity to cross-check the pressure sensors in the reservoir and chamber to ensure that they are similar when the chamber is exhausting to the reservoir. This can be used to detect failure of the pressure sensor or valve malfunction. (2) By exhausting with relatively high / low pressures, there is a large pressure difference relative to the FMS measurement, and therefore better resolution can be obtained.

[0101] The blood flow circuit 141 may also include an air trap 19 incorporated into the blood flow circuit 141. The air trap 19 can be used to remove any air bubbles that may be present in the blood flow path. In some cases, the air trap 19 can separate any air that may be present in the blood by gravity. In some cases, the air trap 19 may also include a port for sampling blood. Air traps are known to those skilled in the art.

[0102] According to another aspect of the present invention, the air trap 19 is positioned in the blood flow path after blood has left the dialysis machine and before it returns to the patient. As shown in Figures 4C and 4D, the air trap 19 may have a spherical or ellipsoidal container 6, with its inlet port 7 located near the top and offset from the vertical axis of the container, and an outlet 9 located at the bottom of the container. Thus, the curved shape of the inner wall 4 of the trap can direct the blood to circulate along the inner wall as it is pulled towards the bottom of the container by gravity, thereby facilitating the removal of air bubbles from the blood. Air present in the blood leaving the outlet 9 of the dialysis machine 14 enters the air trap 19 from the top and remains at the bottom of the container as the blood flows out from the bottom outlet into the venous blood line 204. By positioning the inlet port 7 near the top of the trap 19, it is also possible to circulate blood through a trap with minimal or no air present in the container (as a "run-full" air trap). It may be advantageous to eliminate the air-blood interface for normal blood circulation in the trap. By positioning the inlet port 7 at or near the top of the container, it is also possible to remove most or all of the air present in the trap by reversing the flow of fluid through the blood tube (i.e., from the bottom to the top of the trap 19, and out through the inlet port of the trap 19). In embodiments, a self-sealing port 3, such as a self-sealing stopper with a divided partition or membrane or another configuration, is located at the top of the trap, thereby allowing air to be drawn out of the container (e.g., by a syringe). To facilitate cleaning of the self-sealing port during disinfection, the blood-side of the self-sealing membrane can be positioned substantially coplanar with the top inside the trap. The self-sealing port 3 can also serve as a blood sampling site and / or allow the introduction of liquids, drugs or other compounds into the blood circuit. If needle access is intended, a sealed rubber stopper can be used. Using a self-sealing stopper with a divided partition allows for sampling and fluid delivery using a needle-free system.

[0103] An additional fluid connection 82 also allows the blood flow circuit 10 to be connected to a fluid source for priming or sterilizing the patient and / or the system including the blood flow circuit 10. Generally, during disinfection, the arterial line 203 and venous line 204 are directly connected to the directional circuit 142 via conduits 67, thereby allowing the disinfectant fluid (e.g., hot water, and in some embodiments, a combination of hot water and one or more chemicals) to flow through the dialysis machine 14 and the blood flow circuit 141 back to the directional circuit 142 for recirculation. This disinfection is similar to that described in U.S. Patent No. 5,652,898 by Kenley et al., which is incorporated herein by reference. This will also be described in more detail later.

[0104] The pressure within the arterial line 203 may be maintained at a pressure below atmospheric pressure in some cases to draw blood from the patient. When a pod pump is used, the pressure within the blood flow pump 13 may be inherently limited to the pressure available from the positive and negative pressure reservoirs used to operate the pump. If a pressure reservoir or valve fails, the pump chamber pressure approaches the reservoir pressure. This causes the fluid pressure to rise to match the reservoir pressure until the septum in the pod pump "reaches the bottom" (i.e., can no longer move further to make contact with the surface), and the fluid pressure equilibrium with natural body fluid pressure without exceeding safety limits. This failure causes the pod pump to stop operating spontaneously without any special intervention.

[0105] Figures 30–33 show specific, non-limiting examples of blood flow cassettes. Referring here to Figures 30A and 30B, the outside of the top plate 900 of an exemplary embodiment of the cassette is shown. The top plate 900 includes one half of the pod pumps 820, 828. This half is the liquid half through which the fluid of the supply source flows. Two fluid passages 818, 812 are shown. These fluid passages lead to their respective pod pumps 820, 828.

[0106] The pod pumps 820, 828 include raised channels 908, 910. The raised channels 908, 910 allow fluid to continue flowing through the pod pumps 820, 828 after a partition (not shown) has reached the end of its stroke. Thus, the raised channels 908, 910 minimize the possibility of the partition trapping air or fluid in the pod pumps 820, 828, or of the partition blocking the inlet or outlet of the pod pumps 820, 828 (thereby preventing continuous flow). While the raised channels 908, 910 are shown to have specific dimensions in one exemplary embodiment, in some cases the dimensions are equivalent to those of the fluid channels 818, 812. However, in alternative embodiments, the raised channels 908, 910 may be narrower, or in yet another embodiment, the raised channels 908, 910 may be of any size, since the purpose is to control the fluid flow to achieve a desired flow rate or behavior of the fluid. In some embodiments, the raised channels 908, 910 and the fluid channels 818, 812 have different dimensions. Therefore, the dimensions shown and described herein for the raised channels, pod pumps, valves or any other embodiments are merely illustrative alternative embodiments. Other embodiments are readily apparent.

[0107] In one exemplary embodiment of this cassette, the top plate includes a container perch 904 along with a spike 902. The spike 902 is hollow in this example and is fluid-connected to the flow path. In some embodiments, a needle is mounted inside the spike. In other embodiments, the needle is connected to a container attachment.

[0108] Referring here to Figures 30C and 30D, the inside of the top plate 900 is shown. The raised channels 908 and 910 connect to the inlet channels 912 and 916 and outlet channels 914 and 918 of the pod pumps 820 and 828. The raised channels will be described in more detail later.

[0109] A metering pump (not shown) includes a connection to the hollow passage 902 of the spike, along with a connection to the air vent 906. In one exemplary embodiment, the air vent 906 includes an air filter (not shown). The air filter may optionally be a particulate air filter. In some embodiments, the filter is a somicron hydrophobic air filter. In various embodiments, the size of the filter may be varied, and in some cases, the size is determined by the desired result. The metering pump works by drawing in air from the air vent 906 and pumping the air through the hollow passage 902 of the spike into a container of a second fluid (not shown), and then pumping a certain volume of the second fluid from the container (not shown) into the fluid line at location 826 through the hollow passage 902 of the spike. In Figure 30C, this fluid flow path to the metering pump is indicated by arrows.

[0110] Referring here to Figures 31A and 31B, the liquid side of the intermediate plate 1000 is shown. It shows regions complementary to the fluid channels of the inner top plate. These regions are slightly raised tracks that indicate a surface finish contributing to laser welding, which is a mode of manufacture in one embodiment. The figure also shows the fluid inlet 810 and the fluid outlet 824.

[0111] Next, referring to Figures 31C and 31D, the air side of the intermediate plate 1000 according to one embodiment is shown. The air side of valve holes 808, 814, 816, and 822 corresponds to the fluid side holes of the intermediate plate (shown in Figure 31A). As shown in Figures 33C and 33D, partition wall 1220 completes valves 808, 814, 816, and 822, and partition wall 1226 completes pod pumps 820 and 828. Metering pump 830 is completed by partition wall 1224. Valves 808, 814, 816, 822, 832, 834, and 836 are pneumatically driven, and when the partition wall is pulled away from the hole, liquid is drawn in, and when the partition wall is pushed toward the hole, liquid is pushed through. The fluid flow is directed by opening and closing valves 808, 814, 816, 822, 832, 834, and 836.

[0112] Referring to Figures 31A and 31C, the metering pump includes three holes 1002, 1004, and 1006. One hole 1002 draws air into the metering pump; the second hole 1004 pushes air into the spike / source container and also draws liquid from the source container; and the third hole 1006 pushes the second fluid from the metering pump 830 to location 826 in the fluid line.

[0113] Valves 832, 834, and 836 operate the second fluid metering pump. Valve 832 is the second fluid / spike valve, valve 834 is the air valve, and valve 836 controls the flow of fluid into region 826 of the fluid line.

[0114] Next, referring to Figures 32A and 32B, an internal view of the bottom plate 1100 is shown. An internal view of the operating / air chamber of the pod pumps 820, 828, metering pump 830, and valves 808, 814, 816, 822, 832, 834, 836 is shown. The pod pumps 820, 828, metering pump 830, and valves 808, 814, 816, 822, 832, 834, 836 are driven by a pneumatic air source. Now referring to Figures 32C and 32D, the outside of the bottom plate 1100 is shown. The air supply source is mounted on this side of the cassette. In one embodiment, a tube connects to the characteristic parts of the valves and pump 1102. In some embodiments, the valves are interlocked, and two or more valves are driven by the same air line.

[0115] Referring here to Figures 33A and 33B, an assembled cassette 1200 is shown, comprising a second fluid container (or other source) 1202, which in this embodiment shows a fitted anticoagulant as described above. The container 1202 contains the source of the second fluid and is attached by a container mount 1206 to a hollow spike (not shown). The spike is located within the container mount 1206 and may be oriented upward to penetrate the top of the container 1202, which is held in the opposite position by the container mount 1206. The spike is in fluid communication with a fluid channel similar to the hollow passage 902 shown in Figures 30C and 30D. An air filter 1204 is shown to be attached to an air vent (not shown, shown as 906 in Figure 30A). Not shown in Figure 33A, the upper part of the container (shown as 904 in Figure 30A) is below the container mount 1206.

[0116] In some cases, the metering pump is an FMS pump, which is associated with a reference chamber and can be monitored by a pressure transducer to determine the volume of fluid being discharged. The FMS algorithm uses pressure changes to calculate volume measurements at the end of the filling stroke and the end of the discharging stroke. The difference between the calculated volumes at the end of the filling stroke and the end of the discharging stroke is the actual stroke volume. This actual stroke volume can be compared to the predicted stroke volume for a chamber of a particular size. If the actual volume and the predicted volume differ significantly, the stroke has not been properly completed, and an error message can be generated. The FMS system can be evacuated to an atmosphere for FMS measurements. Alternatively, the system can be evacuated to a positive high-pressure source and a negative low-pressure source for FMS measurements. In one embodiment, the metering pump (e.g., an anticoagulant pump) is primed. By priming the pump, air is removed from the metering pump and the flow path, ensuring that the pressure in the fluid container (e.g., an anticoagulant vial) is acceptable.

[0117] The metering pump can be designed such that air within the pump chamber flows into the vial. To test, close all of the metering pump fluid valves, measure the outer volume, evacuate the pump's FMS chamber to vacuum, open the valves to draw from the vial into the pumping chamber, measure the outer volume (again), apply pressure to the FMS chamber, open the valves to push fluid back into the vial, and then measure the outer volume (again). The change in outer volume due to fluid flow should correspond to the known volume of the pumping chamber. If the pumping chamber cannot be filled from the vial, the pressure in the vial is too low and air must be pumped in. Conversely, if the contents of the pumping chamber cannot be emptied into the vial, the pressure in the vial is too high and some of the anticoagulant must be pumped out of the vial. The anticoagulant pumped out of the vial during these tests can be discarded, for example, through a drain.

[0118] While heparin or other drugs are being normally delivered to the blood path, the pressure within the vial can be periodically measured. If the vial pressure approaches a predetermined threshold below atmospheric pressure, for example, the metering pump can first introduce air into the vial via the metering pump air vent to return the pressure in the vial to normal and help ensure an appropriately accurate amount of drug is withdrawn from the vial. If the vial pressure approaches a predetermined threshold above atmospheric pressure, the metering pump can prevent further air from being injected into the vial prior to the next withdrawal of drug from the vial.

[0119] [[ID=]7] Figures 33C and 33D show exploded views of the assembled fluid pump cassette 1200 shown in Figures 33A and 12B. In some embodiments, this cassette may be adapted for pumping blood. These figures show exemplary embodiments of the partition or membrane 1226 of the pod pump. The partition gasket or bead positions the partition between the pumping chamber and the control chamber of the pump, providing a seal between the fluid chamber (in the pumping side body i.e., the top plate 900) and the air / working chamber (in the control side body i.e., the bottom plate 1100). The recessed ridges of the body i.e., the dome of the partition 1226 provide additional space for air and fluid to leak out of the chamber at the end of the stroke.

[0120] In exemplary embodiments, the partition wall 1226 has a curved, dome-shaped, or hemispherical shape to generally match the shape of the inner wall of the pump chamber and / or control chamber of the pump portion of the pump cassette. Other partition wall shapes are possible if the internal rigid walls of the pumping chamber or control chamber have different shapes. In preferred embodiments, the partition wall separating the pumping chamber from the control chamber of the pump has a shape or contour that generally matches the specific curved contour of the inner wall of the pumping chamber and / or control chamber of the pump portion of the pump cassette. If the rigid inner wall contour of the pump chamber matches that of the control chamber, the partition wall can be shaped to have a contour that generally matches the curved inner wall of the pumping chamber when expanded into the pumping chamber during the fluid discharge stroke, and a contour that generally matches the curved inner wall of the control chamber when expanded into the control chamber during the fluid filling stroke.

[0121] In some embodiments, as shown in Figure 146B, the body 1700 of the flexible partition wall or membrane 1226 has a variable cross-sectional thickness. Thinner, thicker, or variable-thickness membranes can be used to adapt to the strength, bending properties, and other properties of the selected partition material. To control the partition wall, it is also possible to use thinner, thicker, or variable partition wall thicknesses, thereby promoting bending in some areas more easily than in others, thereby aiding in the pumping action and the control of the object in the pump chamber, i.e., the fluid flow. In this embodiment, the partition wall is shown to have its thickest cross-sectional region closest to its center. However, in other embodiments having a partition wall with a variable cross-sectional thickness, the thickest and thinnest regions can be anywhere on the partition wall. Thus, for example, a relatively thin cross-section can be placed near the center of the partition wall, and a relatively thick cross-section can be placed near the periphery of the partition wall. Further configurations are possible. Referring to Figures 147A to 147D, some embodiments of the partition wall are shown to have various raised features, protrusions, or projections on its surface or surface embodiment. Rather than a smooth surface (Figure 147A), these raised features include, for example, raised rings or partially or completely circumferential ridges 1702 (Figure 147B), raised ribs or radial ridges 1704 (Figure 147C), or a plurality of recessed depressions, raised dots or bumps 1706 (Figure 147D), of variable thickness and / or shape, located at various locations on the operating and / or pumping side of the partition. In one embodiment of the partition, the partition has a tangential slope in at least one portion, while in other embodiments, the partition is completely smooth or substantially smooth. Referring now to Figures 148A and 148B, one of the alternative embodiments of the partition is shown. In this embodiment, the partition has a recessed or dotted surface. In a typical structure, the raised features, protrusions or dots 1706 are formed on the surface of the partition facing the liquid pumping chamber of the pump.A favorable forming method involves forming the pumping chamber side of the partition wall convex within the forming cavity, thereby the partition wall body being relaxed or stress-free relative to the periphery of the partition wall (i.e., relative to the bead, gasket, or O-ring component 1708 of the partition wall 1226) when the pumping chamber side of the partition wall is in a convex shape. Thus, the force required to fully expand the partition wall into the pumping chamber during the pumping operation can be reduced, and the partition wall tends to move toward its formed stress-free state during the fluid discharge stroke.

[0122] The partition wall can be fabricated from any flexible material having the desired durability and compatibility with the target fluid being pumped out. The partition wall can be fabricated from any material that can bend in response to the pressure or vacuum of the fluid, liquid, or gas applied to the working chamber. The partition wall material can also be selected for specific biocompatibility, temperature compatibility, or compatibility with various target fluids that may be pumped out by the partition wall or introduced into the chamber to facilitate the partition wall's movement. In exemplary embodiments, the partition wall is fabricated from high-elongation silicone. However, in other embodiments, the partition wall may be fabricated from any elastomer or rubber, including, but not limited to, silicone, urethane, nitrile, EPDM, or any other rubber, elastomer, or flexible material. The partition wall may exhibit elastic properties when stretched beyond its relaxed, non-stressed, or molded shape.

[0123] The shape of the partition wall is determined by several variables. These variables include, but are not limited to, the shape of the chamber, the size of the chamber, the characteristics of the fluid being worked with, the volume of fluid being worked with each stroke, and the means or mode of mounting the partition wall to the housing. The size of the partition wall is determined by several variables. These variables include, but are not limited to, the shape of the chamber, the size of the chamber, the characteristics of the fluid being worked with, the volume of fluid being worked with each stroke, and the means or mode of mounting the partition wall to the housing. Therefore, depending on these or other variables, the shape and size of the partition wall may differ in various embodiments.

[0124] The partition can have any thickness. However, in some embodiments, the thickness ranges from about 0.0508 mm (0.002 inches) to about 3.175 mm (0.125 inches). Depending on the material used for the partition, the desired thickness may vary. In one embodiment, high-elongation silicone with a thickness ranging from about 0.381 mm (0.015 inches) to about 1.27 mm (0.050 inches) is used. However, in other embodiments, the thickness may vary.

[0125] In exemplary embodiments, the partition wall is pre-formed to include a substantially dome-shaped or ellipsoidal (or other curved) shape in at least a portion of the area of ​​the partition wall, such as the body 1700 of partition wall 1226. Figures 149A and 149B show one embodiment of a dome-shaped partition wall. Figure 149B shows a cross-sectional view along the line shown in Figure 149A. In this case as well, the dimensions of the dome may vary based on some or more of the variables described above. However, in other embodiments, the partition wall may not include a pre-formed dome or curved shape.

[0126] In exemplary embodiments, the partition dome is formed using liquid injection molding. However, in other embodiments, the dome can be formed by compression molding. In alternative embodiments, the partition is substantially flat. In other embodiments, the dome size, width, or height may vary.

[0127] In various embodiments, the partition can be positioned in place by various means and methods. In one embodiment, the partition is clamped between several parts of the cassette, and in some of these embodiments, the rim of the cassette may include a feature that grips the bead 1708 of the partition. In other embodiments, the partition is clamped to the cassette using at least one bolt or another device. In another embodiment, the partition is overmolded with a piece of plastic, and then the plastic is welded to the cassette or otherwise attached. In another embodiment, the partition is sandwiched between the pump cassette 1710 intermediate body, i.e., the intermediate plate 1000, and the control side body, i.e., the bottom plate 1100 (see, for example, Figures 146A and 146B). Although several embodiments of attaching the partition to the cassette have been described, any method or means of attaching the partition to the cassette may be used. In one alternative embodiment, the partition is attached directly to a part of the cassette. In some embodiments, the partition wall is thicker at the edge or periphery where it is clamped to the plate than in other areas of the partition wall. In some embodiments, the relatively thicker area is a gasket, in some embodiments an O-ring, a bead element or ring, or any other shape of thickening suitable for compression or welding capture of the intermediate plate 1000 against the bottom plate 1100, or the intermediate plate 1000 against the pumping side, i.e., the top plate 900, of the pump cassette 1710. In some embodiments, two or more gaskets or beads can provide mounting points for the partition wall to the cassette. In other embodiments, the partition wall comprises a single bead or gasket. For example, embodiments in Figures 147A–147D show a partition wall with a single bead or gasket 1708.

[0128] In some embodiments, the gasket, O-ring, or bead 1708 on the periphery of the partition wall is continuous with (or co-molded with) the body 1700 of the partition wall. The transition between the gasket and the main part or body of the partition wall may have a thickness intermediate between the thickness of the gasket or bead and the thickness of the body of the partition wall. Alternatively, the transition between the bead and the body may have a uniform thickness matching the thickness of the body of the partition wall. However, in other embodiments, the gasket or bead may be a separate part of the partition wall. In some embodiments, the gasket or bead is made from the same material as the partition wall. However, in other embodiments, the gasket or bead may be made from a different material than the partition wall. In some embodiments, the gasket or bead is formed by overmolding a ring around the partition wall. The gasket or bead may be a ring or seal of any shape desired to complement the pod pump housing embodiment. In some embodiments, the gasket or bead is a compression type gasket, and it obtains a cross-sectional shape that matches a rigid cassette component that fastens the gasket or bead to the appropriate location.

[0129] As shown in Figure 150, the transition portion 1712 of the partition wall 1226 between the partition wall gasket 1708 and the partition wall body 1700 can be supported, clamped, or fastened between the intermediate body and the control side body. In embodiments, this is achieved by a projection or projection 1714 along the periphery of the opening of the intermediate body 1000 of the pump cassette 1710, the opening being formed to accommodate the movement of the body 1700 of the flexible partition wall 1226 between the control side body, i.e., the control chamber 1716 of the bottom plate 1100, and the pumping side body of the cassette 1710, i.e., the pumping chamber 1718 of the top plate 900. In this embodiment, the clamping feature 1714 is formed from the intermediate body, i.e., the intermediate plate 1000, of the cassette assembly, but a similar feature can be equally effectively formed from the control side body, i.e., the bottom plate 1100, of the cassette assembly and functions to clamp or fasten the transition portion 1712 of the partition wall 1226 between the intermediate body and the control side body.

[0130] As shown in Figures 149A and 149B, the body 1700 of the partition wall 1226 can be molded to have a relaxed or unstressed form, with the pumping chamber side of the partition wall convex relative to the pumping chamber 1718 side of the pump cassette 1710. Thus, when installed in the pump, any elastic tension of the partition wall is reduced when the pumping chamber side of the partition wall is convex and / or minimized when the partition wall is stretched into the pumping chamber. As shown in Figures 150 and 151, in this case, the transition region 1712 between the gasket 1708 of the partition wall 1226 and the body 1700 of the partition wall 1226 can be curved to wrap around the projection 1714 of the intermediate body 1000, thereby essentially draping the partition wall 1226 into the pumping chamber 1718 region. While this configuration may have some advantages in that it allows the septum to be fully positioned with minimal stretching against the pumping chamber wall during the discharge stroke, it has also been unexpectedly found to be associated with some degree of coagulation or fibrous protein chain formation near the junction between the septum and the intermediate in the pumping chamber (where the septum is pinched or squeezed). Although other explanations may exist, there are two possible reasons why the typical septum morphology (a convex, relaxed state relative to the pumping chamber side) may be associated with coagulation when pumping blood. Firstly, the body 1700 of the septum 1226 may or may not be fully positioned within the control chamber 1716 when negative pressure or vacuum is applied to the control chamber 1716 until the transition region 1712 is elastically stretched, resulting in a discontinuity or gap between the septum contact portion of the intermediate 1000 and the surface of the septum near or in the transition region 1712. These discontinuities or gaps can serve as adhesion sites for blood components, thereby leading to blood stagnation and the initiation of coagulation. Alternatively, as the partition is positioned within the pumping chamber during the discharge stroke, the peripheral portion 1720 of the body 1700 of the partition 1226 may trap some blood as the partition naturally attempts to restore its unstressed form to contact the pumping chamber wall 1722 of the intermediate body 1000 or the pumping side body or top plate 900.Such blood containment can lead to the stagnation of blood components and the initiation of coagulation. In either situation (or for other reasons), the septum 1226, which is naturally shaped to exhibit a non-stressed form that is convex toward the pumping chamber wall 1722, may promote the formation of fibrous protein chains or blood clots.

[0131] Surprisingly, it was found that the formation of blood clots or fibrous protein chains in the pumping chamber of the pump cassette could be reduced by changing the design and morphology of the partition wall 1226. As shown in Figures 152A and 152B, in an alternative embodiment, the body 1700 of the partition wall 1226 can be molded such that the relaxed or unstressed state of the partition wall 1226 has a control surface that is convex toward the control chamber 1716 side of the pump cassette 1710, rather than having a pump surface that is convex toward the pumping chamber side of the partition wall. Thus, when installed in the pump, any elastic tension in the partition wall is reduced when the control chamber side of the partition wall is convex and / or minimized when the partition wall is fully extended into the control chamber. In this case, the mold in which the partition wall is molded can have a number of recessed "recesses" located in the convex portion of the mold rather than in the concave portion of the mold. As shown in Figures 153 and 154, in this case, the transition region 1712 between the bead or gasket 1708 of the partition wall 1226 and the body 1700 of the partition wall 1226 appears as it comes into contact with the clamping or pinching portions of the intermediate body i.e., the intermediate plate 1000 and the control side body i.e., the bottom plate 1100, and can therefore naturally curve away from the chamber-facing wall 1722 of the intermediate body 1000 or the pump body or top plate 900 (1724). A possible advantage of this configuration is that when negative pressure is applied to the body 1700 of the partition wall 1226 during the filling stroke, the peripheral portion 1720 of the partition wall 1226 tends to move naturally away from the chamber-facing wall 1722 of the intermediate body 1000. This can help prevent the extension of the transition region 1712 and the occurrence of discontinuities or gaps between the transition region 1712 and the portion of the cassette in contact with the partition wall 1226. Alternatively, during the discharge stroke, the elastic force of the partition wall resisting being positioned within the pumping chamber can prevent the peripheral portion 1720 of the partition wall from coming into full contact with the pumping chamber wall 1722, thus helping to avoid blood trapping and stagnation in that area.Therefore, the elastic recovery force of the partition, which is molded to have a convex shape toward the control chamber wall, can prevent the peripheral region of the partition from coming into complete contact with the pumping chamber wall and potentially trapping any residual fluid within the pumping chamber. In some pump configurations, maintaining the possible space between the partition 1226 and the pumping chamber wall in this peripheral region may be useful when pumping fluids containing protein-containing substances, such as blood or plasma (or other relatively viscous liquids), because it reduces the likelihood of dissolved or suspended compounds agglomerating, adhering, polymerizing, or coagulating in the pump region adjacent to the chamber-facing wall 1722 of the intermediate, i.e., the pumping side of the pumping chamber 1718.

[0132] Alternative embodiments may also serve to prevent the formation of a stagnation region between the peripheral portion 1720 of the body 1700 of the partition wall 1226 and the peripheral portion 1722 of the pumping chamber 1718. For example, the partition wall 1226 can be molded to expand the transition region 1712 between the gasket 1708 and the body 1700 of the partition wall 1226, thereby further widening into the chamber so that when the partition wall 1226 is installed in the pump cassette, the transition region 1712 moves away from the gasket 1708 region and no longer comes into contact with the clamping portion 1712 of the intermediate body 1000 of the cassette 1710. Thus, in the relaxed state, the body 1700 of the partition wall 1226 tends to move more elastically to avoid contact with the chamber-facing side 1722 of the intermediate body (or more generally, the peripheral portion 1722 of the pumping chamber 1718 wall). Optionally, the transition region 1712 of the partition wall 1226 can be shaped to have a thicker cross-section to improve its rigidity and resistance to bending toward the chamber-facing side 1722 of the intermediate body 1000 (or more generally, the peripheral portion 1722 of the chamber wall).

[0133] The system of the present invention may also include a balancing circuit, for example, a balancing circuit 143 as shown in Figure 3A. In some cases, the blood flow circuit is incorporated into the cassette, but this is not always necessary. Within the balancing circuit, the flow of dialysate into and out of the dialyzer can be balanced so that essentially the same amount of dialysate flows out of the dialyzer as the amount entering it (however, this balance may, in some cases, be altered by using a bypass pump, as will be described later).

[0134] Furthermore, in some cases, the flow of dialysate can also be balanced through the dialyzer so that the pressure of the dialysate within the dialyzer is generally equal to the pressure of the blood flowing through the blood flow circuit. In some cases, the flow of blood through the blood flow circuit 141 and the dialyzer is synchronized with the flow of dialysate in the dialysate channel through the dialyzer. Because the fluid may be moved across the semipermeable membrane of the dialyzer, and because the equilibrium circuit pump operates under positive pressure, the equilibrium circuit pump can be timed to synchronize its discharge stroke to the dialyzer with the discharge stroke of the blood pump using pressure and control data from the blood flow pump.

[0135] Figure 5 shows a non-restrictive example of a balance circuit. In the balance circuit 143, dialysate flows from an optional ultrafiltration device 73 into one or more dialysate pumps 15 (for example, two as shown in Figure 5). The dialysate pumps 15 in this figure include two pod pumps 161, 162, two balance chambers 341, 342, and a pump 35 that bypasses the balance chambers. The balance chambers are formed from rigid chambers and may be configured such that the rigid chambers have flexible partitions that divide the chambers into two separate fluid compartments, thereby allowing fluid to be forced out of one compartment by the entry of fluid into the other compartment, or vice versa. Non-limiting examples of pumps that can be used as pod pumps and / or equilibrium chambers are described in U.S. Provisional Patent Application No. 60 / 792,073, filed April 14, 2006, entitled "Extracorporeal Thermal Therapy Systems and Methods," and in U.S. Patent Application No. 11 / 787,212, filed April 13, 2007, entitled "Fluid Pumping Systems, Devices and Methods," each incorporated herein by reference. Further examples of pod pumps are described in detail below. As shown in the schematic diagram in Figure 5, many of the valves can be "interlocked" or synchronized together as a set, thereby allowing all valves in the set to open and close simultaneously.

[0136] More specifically, in one embodiment, flow balancing works as follows. Figure 5 includes a first synchronized, coordinately controlled set of valves 211, 212, 213, 241, and 242, in which valves 211, 212, and 213 are interlocked and valves 241 and 242 are interlocked, as well as a second synchronized, coordinately controlled set of valves 221, 222, and 223, 231, and 232, in which valves 221, 222, and 223 are interlocked and valves 231 and 232 are interlocked. At first time point, the first interlocked set of valves 211, 212, 213, 241, and 242 is open, and the second interlocked set of valves 221, 222, 223, 231, and 232 is closed. Fresh dialysate flows into the balancing chamber 341, while used dialysate flows from the dialyzer 14 to the pod pump 161. Because valve 221 is closed, fresh dialysate does not flow into the equilibrium chamber 342. When fresh dialysate flows into the equilibrium chamber 341, the used dialysate in the equilibrium chamber 341 is pushed out and exits the equilibrium circuit 143 (because valve 223 is closed, the used dialysate cannot enter the pod pump 161). At the same time, the pod pump 162 pushes the used dialysate present in the pod pump into the equilibrium chamber 342 (through the open valve 213, i.e., valves 242 and 222 are closed, ensuring that the used dialysate flows into the equilibrium chamber 342). As a result, the fresh dialysate contained in the equilibrium chamber 342 exits the equilibrium circuit 143 and enters the dialysis machine 14. The pod pump 161 also draws used dialysate from the dialysis machine 14 into the pod pump 161. This is also shown in Figure 18A.

[0137] When the pod pump 161 and the balancing chamber 341 are filled with dialysate, the first set of valves 211, 212, 213, 241, and 242 are closed, and the second set of valves 221, 222, 223, 231, and 232 are opened. Since valve 212 is closed and valve 221 is open, fresh dialysate flows into the balancing chamber 342 instead of the balancing chamber 341. As fresh dialysate flows into the balancing chamber 342, valve 213 is closed, so the used dialysate in the chamber is pushed out and exits the balancing circuit. At the same time, the pod pump 162 draws used dialysate from the dialyzer into the pod pump, and since valve 232 is closed and valve 222 is open, used dialysate is prevented from flowing into the pod pump 161. With valves 232 and 211 closed and valve 223 open, the pod pump 161 pushes the used dialysate contained in the pod pump (from the previous step) into the equilibrium chamber 341. This directs the fresh dialysate contained in the equilibrium chamber 341 into the dialyzer (because valve 241 is open at this time and valve 212 is closed at this time). At the end of this step, the pod pump 162 and the equilibrium chamber 342 are filled with dialysate. This returns the system state to the initial configuration described herein, and thus the cycle can be repeated to ensure a constant flow of dialysate back and forth through the dialyzer. This is also shown in Figure 18B. In embodiments, the fluid (e.g., air) pressure on the control side of the equilibrium chamber valve is monitored to ensure proper functioning.

[0138] As a specific example, a vacuum (e.g., a vacuum of approximately 27.586 kPa (4 psi)) can be applied to the ports for the first set of valve interlocks, thereby opening those valves, while a positive pressure (e.g., approximately 137.931 kPa (20 psi)) (1 psi = 6.896 kPa) can be applied to the second set of valve interlocks, thereby closing those valves (and vice versa). Each pod pump delivers dialysate to one of the spaces in the equilibrium chambers 341 and 342. By forcing the dialysate into the space of the equilibrium chamber, the partition forces an equal amount of dialysate out of the other space within the equilibrium chamber. Within each equilibrium chamber, one space is occupied by fresh dialysate heading to the dialysis machine, and the other space is occupied by used dialysate from the dialysis machine. Thus, the volume of dialysate entering and leaving the dialysis machine is maintained substantially equal.

[0139] It should be noted that any valve associated with the equilibrium chamber can be opened and closed under any suitable pressure. However, it may be advantageous to apply a pressure lower or more controlled than the pressure ultimately used to close and maintain the valve ("holding pressure") in order to initiate and perform valve closure. Applying a pressure equivalent to the holding pressure to bring about valve closure may result in a transient pressure increase in the fluid line to such an extent that an already closed downstream valve may leak, which negatively impacts the equilibrium of the dialysate flow in and out of the dialysate machine. Equilibrium of the dialysate flow in and out of the dialysate machine can be improved by closing the inlet and / or outlet valves of the dialysate pump and equilibrium chamber at a lower or more controlled pressure. In embodiments, for example, this can be done by employing pulse width modulation ("PWM") on the pressure applied to the fluid control line of the valve. Using a moderate or controlled pressure to "softly close" a valve may be effective for reasons such as the following, without being limited to the following theories: (1) In some cases, the pressure in the equilibrium chamber may transiently exceed the holding pressure of the closed equilibrium chamber outlet valve (for example, by applying excessive pressure to close the equilibrium chamber inlet valve against the mass of fluid behind the valve partition). A transient rise in pressure in the fluid line may exceed the holding pressure of the closed outlet valve, thereby causing fluid to leak between the two sides of the equilibrium chamber and resulting in an imbalance in fluid delivery. (2) Also, the presence of air or gas between the equilibrium chamber and the equilibrium chamber valve, which leads to rapid valve closure, may cause excess fluid to be pushed through the equilibrium chamber without equilibrium with the fluid from the other side of the equilibrium chamber.

[0140] As the partition approaches the wall of the equilibrium chamber (therefore, the volume of one side of the equilibrium chamber approaches its minimum and the volume of the other side approaches its maximum), positive pressure is applied to the ports for the first set of valves, thereby closing those valves, while at the same time, a vacuum is applied to the second set of valves, thereby opening those valves. Then, the pod pumps each pump dialysate into one of the spaces in the other of the equilibrium chambers 341 and 342. In this case as well, by forcibly pumping dialysate into the space of the equilibrium chamber, the partition pushes an equal amount of dialysate out of the other space of the equilibrium chamber. In each equilibrium chamber, one space is occupied by fresh dialysate going to the dialysis machine, and the other space is occupied by used dialysate from the dialysis machine, so that the volume of dialysate entering and leaving the dialysis machine is maintained to be equal.

[0141] Figure 5 also shows a bypass pump 35, which can direct the flow of dialysate from the dialyzer 14 through the equilibrium circuit 143 without passing through the pod pumps 161 or 162. In this figure, the bypass pump 35 is a pod pump similar to those described above, and comprises a rigid chamber and a flexible partition dividing each chamber into a fluid compartment and a control compartment. This pump may or may not be the same as the other pod pumps, metering pumps and / or equilibrium chambers described above. For example, this pump could be one of those described in U.S. Provisional Patent Application No. 60 / 792,073, filed April 14, 2006, entitled "Extracorporeal Thermal Therapy Systems and Methods," or in U.S. Patent Application No. 11 / 787,212, filed April 13, 2007, entitled "Fluid Pumping Systems, Devices and Methods," each of which is incorporated herein by reference. Pod pumps will be discussed in more detail later.

[0142] When a control fluid is used to operate this pump, the dialysate can be drawn through the dialyzer so as not to be in equilibrium with the blood flow through the dialyzer. The independent action of the bypass pump 35 on the dialysate outlet side of the dialyzer results in further net ultrafiltration of fluid from the blood in the dialyzer. This can result in a net flow of fluid from the patient through the dialyzer to the drain. Such bypasses can be useful in reducing the amount of fluid the patient has, for example, which is often increased because the patient cannot reduce fluid (mainly water) through the kidneys. As shown in Figure 5, the bypass pump 35 can be controlled by a control fluid (e.g., air) independently of the operation of the pod pumps 161 and 162. This configuration allows for easy control of net fluid removal from the patient without the need to operate equilibrium pumps (internal dialysate pump and external dialysate pump) to draw such fluid from the patient. Using this configuration, it is not necessary to operate the internal dialysate pump so as not to be in equilibrium with or out of phase with the blood pump to perform net fluid withdrawal from the patient.

[0143] To balance the flow across the dialysis machine, the blood flow pump, the balancing circuit pump, and the directioning circuit pump (described later) can be operated in cooperation to ensure that the flow entering the dialysis machine is roughly equal to the flow leaving the dialysis machine. If ultrafiltration is required, the ultrafiltration pump (if any) can be operated independently of some or all of the other blood pumps and / or dialysate pumps to achieve the desired ultrafiltration rate.

[0144] To prevent degassing of the dialysate, the equilibrium circuit pump may always be maintained at a pressure higher than atmospheric pressure. In contrast, the blood flow pump and directional circuit pump use a pressure below atmospheric pressure to pull the partitions toward the chamber wall for the filling stroke. Because the fluid may move across the dialyzer, and because the equilibrium circuit pump operates under positive pressure, the equilibrium circuit pump can use information from the blood flow pump to operate in a balanced flow mode. Thus, the discharge stroke of the dialyzer's equilibrium circuit chamber can be synchronized with the discharge stroke of the blood pump.

[0145] In one embodiment, when operating in this equilibrium mode, if there is no discharge pressure from the blood flow pump, the partition of the equilibrium circuit pump pushes fluid across the dialysis machine into the blood, and another pod of the equilibrium circuit is not fully filled. For this reason, the blood flow pump reports when it is actively discharging a stroke. When the blood flow pump is discharging a stroke, the equilibrium pump operates. When the blood flow pump is not discharging blood, the valves that control the flow from the dialysis machine to the equilibrium pump (and other equilibrium valves that work in conjunction with these valves as described above) can be closed to prevent any fluid movement from the blood side to the dialysate side. While the blood flow pump is not discharging, the equilibrium pump effectively freezes, and when the blood flow pump starts discharging again, the stroke continues. To ensure that the pump operates above atmospheric pressure with minimal impedance, the equilibrium pump filling pressure can be set to the smallest positive value. Also, to roughly match the pressures on both sides of the dialysis machine and minimize the flow across the dialysis machine during the discharge stroke of the internal pump, the equilibrium pump discharge pressure can be set to the blood flow pump pressure.

[0146] In some cases, it may be advantageous for the dialysis pump to discharge dialysate to the dialysis machine at a pressure higher than the discharge pressure of the blood pump to the dialysis machine. This can help ensure, for example, that a full chamber of clean dialysate can be delivered to the dialysis machine. In embodiments, the discharge pressure in the dialysate pump is set high enough for the internal pump to complete its stroke, but not high enough to stop the blood flow in the dialysis machine. Conversely, when the dialysate pump is receiving used dialysate from the dialysis machine, it may also be advantageous in some cases to set the pressure inside the dialysate pump lower than the outlet pressure on the blood side of the dialysis machine. This can help ensure that the receiving dialysate chamber is always filled, thereby ensuring that there is enough dialysate to complete a full stroke in the equilibrium chamber. The flows across the semipermeable membrane resulting from these pressure differences tend to cancel each other out, otherwise the pump algorithm will attempt to match the average pressures on the dialysate and blood sides of the dialysis machine.

[0147] The convection generated across the membrane of the dialysis machine, a constant and repeated shift (which does not result in net ultrafiltration) back and forth across the dialysis machine in small increments, can nevertheless help prevent the formation of blood clots in the blood tubules and within the dialysis machine, thereby enabling a reduction in heparin dosage, extending the service life of the dialysis machine, and facilitating the cleaning and reuse of the dialysis machine, thus potentially being beneficial. Backflushing has the further advantage of promoting better solute removal by convection. In another embodiment, a continuous form of backflushing across the membrane of the dialysis machine can also be performed by making slight adjustments to the synchronization of the blood discharge stroke with the dialysate discharge stroke through the dialysis machine.

[0148] In some embodiments, the pod pump 15 (Figure 89) of the internal dialysate cassette 143 can be phase-adjusted to minimize blockage on the blood side of the dialyzer 14. The internal dialysate pop pump 15 can be phase-adjusted to act with the blood pump 13 to alternately flow fluid back to the blood side and dialysate side of the dialyzer 14 with each stroke of the internal dialysate pump 15. The timing of pump strokes, valve opening, valve closing, and pop pump operating pressure can be controlled by an automatic computer 6106. The automatic computer can control the pumps and valves and receives pressure data via a pneumatic distribution module 9000. Phase-adjusting the internal dialysate pump to push the fluid back and forth across the dialyzer membrane has advantages, including, but is not limited to, facilitating the removal of large solute molecules from the blood and minimizing blockage of the dialyzer.

[0149] The flow through the dialysis machine 14 can be controlled by pumps and valves schematically shown in Figure 89. Figure 12K plots an example of the timing and function of the blood pump and dialysate pump. The blood pump pod pumps 23a and 23b can operate with a phase difference of approximately 180 degrees to provide a nearly continuous flow of blood to the dialysis machine 14. Clean blood and some dialysate fluid can flow from the dialysis machine to the venous line 204 in the BTS. Fresh dialysate can flow into the dialysis machine from the equilibrium pod 342, while used dialysate and fluid from the blood side flow into the receiving pod pump 161. Clean dialysate can flow out of the equilibrium pod 342 when the other dialysate pump 162 forces used dialysate into the equilibrium pod 342. Used dialysate and clean dialysate are separated by a partition. The other equilibrium pod 341 can be filled with fresh dialysate from the external dialysate pump 159 in preparation for the next pump stroke.

[0150] By opening the downstream valve and closing the upstream valve, the pod pressure measured by 193 can be increased, allowing blood to be discharged from the blood pump 23A to the dialysis machine 14. By opening the upstream valve and closing the upstream line, the pressure can be reduced to below the ambient pressure measured by 197, allowing blood to be filled from the arterial line to the blood pump 23b.

[0151] One exemplary procedure for pushing and drawing fluid across the membrane of the dialysis machine can be initiated at time 12411, with blood pump 23b being filled while blood pump 23A discharges blood into the dialysis machine. The measured pressures of the discharge and filling pumps are plotted at 12420 and 12430, respectively. Pressures 12420 and 12430 can be periodically varied in response to variable valves 198 and 199 changing the size of the valve ports sinusoidally. An automatic computer 6106 can monitor pressure traces 12420 and 12430 to detect the end of a stroke in the blood pump.

[0152] The internal dialysate pump and valves can be controlled to allow fluid from the blood in the dialysis machine 14 to flow into the receiving dialysate pump pod 161 between time points 12411 and 12412. Valve 231 can be closed to block the flow of clean dialysate to the dialysis machine 14. Valve 232 can be opened, and the pump pod pressure 12440 can be lowered to allow fluid from the blood to flow into the dialysate pump pod 161. The blood pump 13 can circulate blood through the dialysis machine during this period 12410.

[0153] Between time points 12412 and 12413, the internal dialysate valves and pumps can be controlled to allow dialysate to flow through the dialyzer, with the flow across the membrane of the dialyzer being zero or minimal. The air pressure 12450 in the pump pod 162 can open valves 231 and 213 so that clean dialysate can be forced from the equilibrium pod 342 through the dialyzer 14 into the pump pod 162. The pump 162 can forcibly draw clean dialysate from the equilibrium pod 342 by allowing used dialysate to flow behind the membrane 341C. The blood pump 13 can continue to supply blood to the dialyzer during this period. The pressure in the pump pods 161 and 162 can be periodically changed in accordance with the variable valves 163 and 164 changing the size of the valve ports sinusoidally. The automatic computer 6106 can monitor pressure traces 12440 and 12450 to detect the end of a stroke in the dialysate pump 15.

[0154] During the final part of the dialysate pump stroke, dialysate can flow into the blood side of the dialysis machine. The receiving pump pod 161 can be fully filled at time 12413, while the dispensing pump 162 continues to pump fresh dialysate from the equilibrium pod 342 until time 12414. There is no possibility that the dialysate from the equilibrium pod cannot enter the full pump pod 161; instead, it can flow across the membrane of the dialysis machine and enter the blood circuit. The blood pump 13 can continue to supply blood to the dialysis machine for part or all of this period. While we do not wish to be bound by any theory, it is conceivable that the dialysate flowing into the blood side of the dialysis machine can remove relatively large solutes from the pores, center, and ends of the membrane tubing. Once removed from the surface, the relatively large solutes are more likely to flow through or across the membrane.

[0155] In one exemplary method, the operation of the dialysate pumps 161 and 162 can be stopped, while if the receiving pump pod 161 is not full, the blood pump 13 switches from one pump pod to the other. The dialysate pumps can be stopped to avoid incorrect stroke termination due to pressure signals from the switching blood pump. If the automatic computer 6106 detects a stroke completion condition for the blood pump 13 before the receiving pump pod 161 is full, it can close the equilibrium chamber outlet valve 231 and the pump inlet valve 232. When the blood pump restarts, valves 231 and 232 can be opened again. If the blood pump pod completes its stroke after the receiving pump pod 161 is full, the blood pump waits until the discharging pump pod 162 completes its stroke. The automatic computer can determine that a pump pod stroke is complete or that the dialysate pump pod is full based on a phase function for determining the stroke completion condition.

[0156] To ensure the desired direction of dialysate and blood flow without damaging the membrane of the dialysis machine, the pump pod pressure in the dialysate circuit can be optimally set. The pressure in the discharge pod pump 162 can be set approximately 7.199 kPa (54 mmHg) higher than the blood discharge pressure. The receiving pump pod 161 can be adjusted to the higher of either approximately 3.333 kPa (25 mmHg) higher than the ambient pressure or the blood discharge pressure minus the intermembrane pressure. After filling or when the receiving pump pod 162 is full, the discharge pump pod pressure can be increased to the maximum intermembrane pressure of the dialysis machine.

[0157] In one exemplary method, the variable valves in blood pumps 198, 199 can be circulated at a different frequency than the variable valves in dialysate pumps 163, 164, so that stroke end detection for each pump can be measured separately. As described elsewhere, the throttle of the variable valves in the pump pods changes sinusoidally around the mean value. This small change in throttle causes a similarly small change in the measured pressure in the start chamber. A correlation filter, described elsewhere, generates a numerical measure of how well the pressure responds to the variable valve fluctuations. Using the resulting phase function, stroke end can be determined. Pressure fluctuations in blood pump pod 23a can be detected by a sensor in filling pump pod 161, which may result in incorrect stroke end readings. However, the correlation filter rejects pressure signals at frequencies different from the variable valve frequency. To isolate the pressure signals from the two pumps 161, 23a, the variable valves can be dithered at 90% of the frequency at which the blood pump variable valves dither.

[0158] In one exemplary method, the discharge pump delay 12410 is optimally adjusted to discharge a desired amount of dialysate into the blood circuit at the end of a dialysate stroke. A simple proportional closed-loop controller modulates the discharge pump delay 12410 to achieve a desired time for dialysate flow into the blood circuit 12416. The controller can adjust the pump delay time to accommodate changes in flow impedance on the blood side and / or dialysate side of the flow circuit, or changes in the membrane impedance of the dialyzer.

[0159] The procedure is then repeated, with pump pod 162 acting as the receiving pump, initiating the process of receiving fluid from the blood side of the dialysis machine, while the discharging pump 161 remains fixed. Both pumps 161 and 162 move until the receiving pump 162 is full. At this point, pump 161 continues to discharge dialysate to the blood side.

[0160] One exemplary method involves using a pump, valves, and a balancing chamber to create a small, periodic flow that reciprocates across the dialysis machine. Other methods and pump / valve embodiments are contemplated.

[0161] The hardware described for the internal dialysate and blood cassette, as well as the method for adjusting the phase of the dialysate, constitutes one implementation. The same method for adjusting the phase of one or more pumps on at least one side of a semipermeable filter to periodically force the fluid to reciprocate across the filter can be applied to the flow of fluid through other semipermeable filters, including, but not limited to, ultrafiltration devices.

[0162] Because stagnant blood flow can lead to blood clotting, it is generally beneficial to maintain continuous blood flow as much as possible during treatment. Furthermore, if the discharge flow rate in the blood flow pump is discontinuous, the balance pump must pause its stroke more frequently, resulting in discontinuous and / or reduced flow rates of dialysate.

[0163] However, the flow through the blood flow pump can be discontinuous for various reasons. For example, to provide a safe discharge pressure for the patient, the pressure may be limited within the blood flow pump to, for example, approximately +79.993 kPa (+600 mmHg) and / or approximately -46.662 kPa (-350 mmHg). For example, during dual needle flow, the two pod pumps of the blood flow pump can be programmed to operate 180° out of phase with each other. If there were no pressure limitations, this phase adjustment could always be done. However, these pressures are limited to provide a safe blood flow for the patient. If the impedance is high in the filling stroke (due to a small needle, very high blood viscosity, insufficient patient access, etc.), a negative pressure limit may be reached, and the filling flow rate will be slower than the desired filling flow rate. Therefore, the discharge stroke must wait until the preceding filling stroke is complete, which results in a pause in the discharge flow rate of the blood flow pump. Similarly, during single-needle flow, the blood flow pump may be operated at 0° phase, where the two blood flow pump pod pumps are simultaneously emptied and filled. When both pod pumps are filled, the capacities of the two pod pumps are discharged. In embodiments, the startup procedure fills the first pod pump, then the second pod pump, and then the first pod pump, then the second pod pump, is emptied. Thus, the flow in a single-needle or single-lubricant configuration may be discontinuous.

[0164] One way to control the pressure saturation limit is to restrict the desired flow rate to the slowest flow rate during the filling and discharging strokes. This results in a slower blood discharge flow rate, but the flow rate is still known and always continuous, thereby providing a more accurate and continuous dialysate flow rate. Another way to make the blood flow rate more continuous in a single-needle operation is to use the maximum pressure to fill the pod, thus minimizing the filling time. The desired discharging time can then be set to the desired total stroke time minus the time taken for the filling stroke. However, if the blood flow rate cannot be made continuous, the dialysate flow rate may have to be adjusted to be higher than the programmed value when the blood flow is discharging to compensate for the time when the dialysate pump is stopped while the blood flow pump is filling. The less continuous the blood flow, the more the dialysate flow rate may have to be adjusted upwards during blood discharge to the dialysis machine. If this is done with precise timing, the average dialysate flow rate obtained over several strokes can still match the desired dialysate flow rate.

[0165] Figures 34 to 36 show non-limiting examples of balanced cassettes. In one cassette structure shown in Figure 34A, the valves are interlocked to be driven simultaneously. In one embodiment, there are four interlocking pairs of valves 832, 834, 836, and 838. In some cases, the interlocking valves are driven by the same air line. However, in the embodiments shown, each valve has its own air line. By interlocking the valves as shown in the exemplary embodiments, the fluid flow described above is generated. In some embodiments, interlocking the valves also ensures that the appropriate valves are opened and closed to define the fluid path as required.

[0166] In this embodiment, the fluid valve is a volcano valve, as will be described in more detail herein. While the fluid flow path outline has been described in relation to a specific flow path, in various embodiments the flow path may differ based on the operation of the valve and pump. Furthermore, the terms inlet and outlet, as well as first fluid and second fluid, are used solely for illustrative purposes (for this cassette and similarly for other cassettes described herein). In other embodiments, the inlet may be the outlet, and similarly, the first fluid and second fluid may be different fluids or different types or compositions of fluids.

[0167] Referring to Figures 35A to 35E, the top plate 1000 of an exemplary embodiment of the cassette is shown. Referring first to Figures 35A and 35B, a top view of the top plate 1000 is shown. In this exemplary embodiment, the pod pumps 820, 828 and the equilibrium pods 812, 822 of the top plate are similarly formed. In this embodiment, the total capacity of the pod pumps 820, 828 and the equilibrium pods 812, 822 when assembled with the bottom plate is 38 ml. However, in various embodiments, the total capacity may be larger or smaller than that in this embodiment. The first fluid inlet 810 and the second fluid outlet 816 are shown.

[0168] Referring here to Figures 35C and 35D, the bottom view of the top plate 1000 is shown. This figure shows the fluid channels. These fluid channels correspond to the fluid channels shown in Figure 34B in the intermediate plate 900. The tops of the top plate 1000 and the intermediate plate form the liquid or fluid side of the cassette with respect to the pod pumps 820 and 828, and to one side of the equilibrium pods 812 and 822. Thus, the majority of the liquid flow path is located in the top plate and intermediate plate. The other side of the flow path of the equilibrium pods 812 and 822 is located inside the bottom plate, which is not shown here, as shown in Figures 36A and 36B.

[0169] Still referring to Figures 35C and 35D, the pod pumps 820, 828 and the equilibrium pods 812, 822 include a groove 1002. While the groove 1002 is shown to have a specific shape, in other embodiments, the shape of the groove 1002 can be any desired shape. The shapes shown in Figures 35C and 35D are exemplary embodiments. In some embodiments of the groove 1002, the groove forms a passage between the fluid inlet and fluid outlet sides of the pod pumps 820, 828 and the equilibrium pods 812, 822.

[0170] The groove 1002 provides a fluid passage so that when the partition is at the end of the stroke, there is still a fluid passage between the inlet and outlet, thereby preventing a pocket of fluid or air from being trapped in the pod pump or equilibrium pod. The groove 1002 is included on both the liquid side and the air side of the pod pumps 820, 828 and the equilibrium pods 812, 822 (see Figures 36A-36B for the air side of the pod pumps 820, 828 and the opposite side of the equilibrium pods 812, 822).

[0171] In one exemplary embodiment, the liquid side of the pod pumps 820, 828 and the equilibrium pods 812, 822 includes the feature that the inlet and outlet channels are continuous, but the outer ring 1004 is also continuous. This feature allows for the maintenance of a seal formed in a partition (not shown).

[0172] Referring to Figure 35E, a side view of an exemplary embodiment of the top plate 1000 is shown. The continuous outer ring 1004 of the pod pumps 820, 828 and the equilibrium pods 812, 822 is also shown.

[0173] Referring here to Figures 36A to 36E, the bottom plate 1100 is shown. Referring first to Figures 36A and 36B, the inner surface of the bottom plate 1100 is shown. The inner surface is the side that contacts the bottom surface of the intermediate plate (not shown, see Figure 34E). The bottom plate 1100 is attached to the air line (not shown). The corresponding inlet holes for air that operate the pod pumps 820, 928 and the valves of the intermediate plate (not shown, see Figure 34E) are shown by 1106. Holes 1108 and 1110 correspond to the second fluid inlet and second fluid outlet shown in Figures 34C, 824 and 826, respectively. The corresponding halves of the pod pumps 820, 828 and the equilibrium pods 812, 822 are also shown as grooves 1112 for the fluid passages. Unlike the top plate, the corresponding halves of the bottom plates of the pod pumps 820, 828 and the equilibrium pods 812, 822 clearly distinguish them from the equilibrium pods 812, 822. The pod pumps 820, 828 include an air passage in the second half of the bottom plate, while the equilibrium pods 812, 822 have the same structure in the half of the top plate. In this case as well, the equilibrium pods 812, 822 equilibrium a liquid and therefore both sides of a partition (not shown) include liquid fluid passages, while the pod pumps 820, 828 are pressure pumps that pump liquid and therefore one side is a liquid fluid passage, and the other side shown on the bottom plate 1100 includes an air-operated chamber or air-fluid passage.

[0174] In one exemplary embodiment of the cassette, sensor elements are incorporated into the cassette to identify various characteristics of the fluid being dispensed. In one embodiment, three sensor elements are included. In one embodiment, the sensor elements are located in a sensor cell 1114. Cell 1114 houses the three sensor elements in sensor element housings 1116, 1118, and 1120. In the embodiment, two of the sensor housings 1116 and 1118 house conductivity sensor elements, and the third sensor element housing 1120 houses a temperature sensor element. Conductivity sensor elements and temperature sensor elements can be any conductivity sensor element or temperature sensor element in the art. In one embodiment, the conductivity sensor element is a graphite post. In other embodiments, the conductivity sensor element is a post made of stainless steel, titanium, platinum, or any other metal that is coated to be corrosion-resistant but still conductive. The conductivity sensor element may include electrical leads that transmit probe information to a controller or other device. In one embodiment, the temperature sensor is a thermistor embedded in a stainless steel probe. In alternative embodiments, the cassette may have no sensors, or only a temperature sensor, or only one or more conductivity sensors, or one or more of other types of sensors. In some embodiments, the sensor elements may be located in a separate cassette outside the main cassette and connected to the cassette via fluid lines.

[0175] Referring still to Figures 36A and 36B, the operating side of the metering pump 830 is also shown, along with the corresponding air inlet hole 1106 for the air that operates the pump. Referring now to Figures 36C and 36D, the outside of the bottom plate 1100 is shown. The air line connection points 1122 for the valves, pod pumps 820, 828 and metering pump 830 are shown. In this case again, the equilibrium pods 812, 822 do not have air line connection points because they are not driven by air. Similarly, the corresponding openings in the bottom plate 1100 for the second fluid outlet 824 and the second fluid inlet 826 are shown.

[0176] Referring now to Figure 36E, a side view of the bottom plate 1100 is shown. The side view shows a rim 1124 surrounding the inner bottom plate 1100. The rim 1124 is raised and continuous and provides a connection point to a bulkhead (not shown). The bulkhead rests on this continuous and raised rim 1124 and provides a seal between the halves of the pod pumps 820, 828 and equilibrium pods 812, 822 of the bottom plate 1100 and the halves of the pod pumps 820, 828 and equilibrium pods 812, 822 of the top plate (not shown, see Figures 35A to 35D).

[0177] As described above, the dialysate flows from the directional circuit, optionally through the heater and / or the ultrafiltration unit, to the equilibrium circuit. In some cases, the directional circuit is incorporated into the cassette, but this is not always necessary. An example of a directional circuit is shown as directional circuit 142 in Figure 3A. In this example, directional circuit 142 can perform several different functions. For example, dialysate flows from the dialysate supply unit (e.g., from the mixing circuit, as described later) through the directional circuit to the equilibrium circuit, while used dialysate flows from the equilibrium circuit to the drain. The dialysate can be flowed by the operation of one or more pumps contained within the directional circuit. In some cases, the directional circuit may also include a dialysate tank, which can contain dialysate before passing it to the equilibrium circuit. Such a dialysate tank can, in some cases, allow the rate of dialysate production to differ from the rate of dialysate use by the dialyzer in the system. The directional circuit can also direct water from the water supply unit to the mixing circuit (if present). Furthermore, as mentioned above, for some operations, such as disinfection, the blood flow circuit can be fluidly connected to the directional circuit.

[0178] Therefore, in some cases, dialysate can be prepared as needed, thereby eliminating the need to store large quantities of dialysate. For example, the prepared precipitate can be held in the dialysate tank 169. A dialysate valve 17 can control the flow of dialysate from the tank 169 into the dialysis machine 20. The dialysate can be filtered and / or heated before being sent to the dialysis machine 14. A waste valve 18 can be used to control the flow of used dialysate out of the dialysate circuit 20.

[0179] Figure 6 shows one non-limiting example of a directional circuit. In this figure, the directional circuit 142 fluidly connects the dialysate from the dialysate supply unit to the dialysate tank 169, and then to the dialysate pump 159, heater 72, and ultrafiltration unit 73, before it enters the equilibrium circuit, as described above. This figure shows the dialysate in the dialysate flow path flowing from the dialysate supply unit to the dialysate tank, pump, heater, and ultrafiltration unit (in that order), but it should be understood that other orders are possible in other embodiments. The heater 72 can be used to heat the dialysate to body temperature and / or to a temperature such that the blood in the blood flow circuit is heated by the dialysate and the blood returning to the patient is above body temperature. The ultrafiltration unit 73 can be used to remove any pathogens, pyrogens, etc. that may be present in the dialysate, as will be described later. The dialysate then flows into the equilibrium circuit so that it is directed towards the dialysis machine.

[0180] The dialysate tank 169 may contain any suitable material and may be of any suitable dimensions for storing dialysate before use. For example, the dialysate tank 169 may include plastic, metal, etc. In some cases, the dialysate tank may contain a material similar to that used to form a pod pump as discussed herein.

[0181] The flow of dialysate through the directional circuit 142 can be controlled (at least partially) by the operation of the dialysate pump 159. Furthermore, the dialysate pump 159 can control the flow through the equilibrium circuit. For example, as described above with reference to Figure 5, fresh dialysate from the directional circuit flows into the equilibrium chambers 341 and 342 of the equilibrium circuit 143, and the pump 159 can be used as the driving force to cause the fresh dialysate to flow into these equilibrium chambers. In one embodiment, the dialysate pump 159 includes a pod pump similar to that described above. The pod pump includes a rigid chamber, which has a flexible partition dividing each chamber into a fluid compartment and a control compartment. The control compartment can be connected to a control fluid source, such as an air source. Non-limiting examples of pumps that can be used as pod pumps and / or equilibrium chambers are described in U.S. Provisional Patent Application No. 60 / 792,073, filed April 14, 2006, entitled "Extracorporeal Thermal Therapy Systems and Methods," or in U.S. Patent Application No. 11 / 787,212, filed April 13, 2007, entitled "Fluid Pumping Systems, Devices and Methods," which are incorporated herein by reference. Pod pumps are described in further detail below. (heater) After passing through pump 159, the dialysate can flow to a heater, for example, heater 72 in Figure 6. The heater may be any heating device suitable for heating the dialysate, such as an electrical resistance heater, as is known to those skilled in the art. The heater may be kept separate from the directional circuit (for example, as shown in Figure 3A), or the heater may be incorporated into the directional circuit or similarly into other circuits (for example, the balancing circuit).

[0182] In one non-limiting example, the heater may comprise a heater cartridge, a metal tube providing a fluid passage, a casting, and one or more temperature sensors. The metal tube may be a coil of stainless steel tubing. The casting may be zinc or aluminum, overmolded into the stainless steel coil and containing a cavity to receive the heater cartridge. The temperature sensors may include, for example, a thermistor, a resistance temperature detector (RTD), or a thermocouple, which are wired to provide the heater temperature to a controller. To provide hardware over-temperature protection, a thermal switch or fuse may be mounted in the casing and wired in series with the cartridge heater. In one embodiment, the cartridge heater may be designed to operate at approximately 110 VAC and provide a thermal output of about 1 kW. In another embodiment, the cartridge heater may be designed to operate at approximately 220 VAC and provide a thermal output of about 1 kW.

[0183] In another embodiment, a cartridge heater may incorporate two or more heater elements that can be energized independently. For example, a single heater cartridge may include two 500W heater elements. To reduce the magnitude of the change in current through the heater when the heater elements are powered on or off, power can be supplied sequentially to multiple independent heater elements. This can reduce voltage fluctuations in the power supply that powers other devices on the same circuit, such as overhead lights. Supplying heater power to multiple independent heater elements using sequential or phase-shifted onboarding can help meet regulatory constraints regarding voltage fluctuations or flicker (see, for example, the International Electrotechnical Commission Standard on Electromagnetic compatibility (IEC61000-3-3)).

[0184] In some cases, the dialysate is heated to a temperature such that the blood passing through the dialyzer is not significantly cooled. For example, the temperature of the dialysate can be controlled so that it is at or above the temperature of the blood passing through the dialyzer. In such cases, the blood can be heated somewhat, which may be useful in offsetting the heat loss caused by the blood passing through the various components of the blood flow circuit, as described above. Furthermore, as will be discussed later, a heater may be connected to the control system so that the dialysate that is incorrectly heated (i.e., the dialysate is too hot or too cold) can be recirculated (e.g., returned to the dialysate tank) or sent to the drain instead of being passed to the dialyzer via line 31, for example (see Figures 3a, 6, or 122). The heater may be integrated as part of a fluid circuit such as a directional circuit and / or a balancing circuit, or, as shown in Figure 3A, the heater may be a separate component in the dialysate flow path.

[0185] The heater can also be used in some embodiments for disinfection or sterilization purposes. For example, water can be passed through a hemodialysis system and heated using a heater so that the water is heated to a temperature at which disinfection or sterilization can occur, such as at least about 70°C, at least about 80°C, at least about 90°C, at least about 100°C, at least about 110°C, etc. In some cases, the water can be recirculated to various components and / or heat loss in the system can be minimized (for example, as described later) so that the heater can heat the water to such disinfection or sterilization temperatures.

[0186] The heater may include a control system that can control the heater as described above (for example, to raise the dialysate to body temperature for dialysis of a patient, or to raise the water temperature to a disinfection temperature for cleaning the system).

[0187] Non-limiting examples of heater controllers are as follows: The controller may be selected to handle pulsating flow or variable flow velocity along with changing inlet fluid temperature. Furthermore, the heater control must function properly when the flow is directed to pass through each of the different flow paths (dialysis, disinfection, recirculation, etc.). In one embodiment, the heater controller is used on the SIP1 board together with the IR (infrared) temperature sensor of the ultrafiltration unit and the IR temperature sensor of the tank. In another embodiment, the board is in a box with low heat loss and uses a conductivity sensor for the inlet temperature sensor. Another embodiment of the controller uses a simple proportional controller that uses the temperatures of both the tank (heater inlet) and the ultrafiltration unit (heater outlet). For example, powerHeater = massFlow * ((tankPGain * errorTank) + (UFPGain * errorUF) In the formula, PowerHeater = heater duty cycle command (0%~100%), MassFlow = fluid mass flow velocity, TankPGain = proportional gain for the tank or inlet temperature sensor, ErrorTank = difference between the tank or inlet temperature sensor and the desired temperature, UFPGain = proportional gain for the ultrafiltration device or outlet temperature sensor, ErrorUF = difference between the uf or outlet temperature sensor and the desired temperature.

[0188] A PWM command is generated from the heater duty cycle command (0% to 100%). In some embodiments, the controller can reduce the mass flow rate if the heater becomes saturated and a given temperature is not maintained. (Heater control unit) An alternative embodiment of the heater 72 in Figure 122 may include a dialysate flow path through which an electric heater element and a heater temperature sensor are complemented by temperature sensors located in the fluid path upstream and downstream of the heater. Temperature sensor 254 is located just upstream of the heater and provides information about the temperature of the incoming fluid. Redundant temperature sensors 252 and 251 are placed downstream of the ultrafiltration unit 73 to measure the temperature of the dialysate entering the internal dialysate cassette, as the dialysate temperature may affect the temperature of the blood returning to the patient. A temperature sensor 255 may be placed in line 731 to measure the flow diverted from the internal cassette.

[0189] Referring to Figure 89, in exemplary embodiments, fluid temperature can be measured at various locations, such as in the equilibrium or internal dialysate circuit 143, in the directional or external dialysate circuit 142, in the ultrafiltration pump circuit 35, in the mixing circuit 25, and / or in the drain line 31, and at the inlet of the heater 72. The heater controller can change the output of the heater 72 based on the measured temperatures from one or more of these temperature sensors. The specific fluid temperature sensor selected for control may be based on the existing dialysate fluid flow path used at a given time (e.g., during treatment, during treatment paused by continuous dialysate recirculation through the ultrafiltration unit 73, during dialysate generation, etc.). For example, pausing or pausing the dialysis operation may include the controller closing valves in the internal dialysate circuit to stop the flow of dialysate through the equilibrium circuit and the dialyzer. In some cases, it may be advantageous to keep the dialysate flowing so that it is recirculated from the dialysate tank through the external dialysate pump to the dialysate tank or optionally directed to the drain. A temperature sensor can be placed in the recirculation or drain channel, or in the upstream channel common to each destination but downstream of the heater 72, for feedback to a controller that controls the heater 72. This configuration allows the heater 72 to maintain a predetermined temperature for the dialysate being drawn from or recirculated to the dialysate tank. Thus, when dialysis is restarted, fresh dialysate at a predetermined or desired temperature is more quickly available for discharge to the equilibrium circuit and dialysis machine. Furthermore, temperature feedback during the continuous flow of dialysate through the heater 72 (optionally at a slower maintenance flow rate) helps prevent overheating of the dialysate during pauses or pauses in dialysis. In some embodiments, an ultrafiltration device may optionally be located either upstream or downstream of the heater 72 in this recirculation or drain channel.

[0190] Referring to Figure 123A, in an alternative embodiment, the "heater control mode" consists of a control loop 608 around the heater. In this embodiment, the heater control mode raises the heater temperature 612 to a desired temperature 610 by outputting duty cycle commands to the heater 72 using a closed-loop controller instead of a simple proportional-integral controller. In another example, the closed-loop controller is a proportional controller. The heater temperature 612 is measured by a heater temperature sensor. The heater temperature sensor is in thermal contact with a flow conduit in the heater 72. The heater temperature sensor can also be incorporated into the heater 72.

[0191] The duty cycle command can be converted into a pulse-width modulation ("PWM") command at a fundamental frequency of 1 Hz. The heater current can be controlled by the PWM command via an SCR electronic circuit that switches the zero crossover on and off. The heater current can also be controlled by a transistor switch (FET, IGBT, or BJT, etc.). Assuming a 60 Hz power supply frequency, a 1 Hz PWM frequency allows for a resolution of 1 / 60.

[0192] In another embodiment, the PWM (pulse width modulation) command has a fundamental frequency of 1 / 4 Hz, so that the heater element is on for part of 4 seconds, off for the rest of 4 seconds, and then the cycle repeats. In one embodiment where two or more heater elements are present, the controller can supply power to the elements with different PWM signals. In one example, the heater elements can be driven at the same frequency, but the signals can be delayed or phase-shifted so that two or more elements are not turned on at the same time. By not applying power to all heater elements at a given time, the change in current is minimized, and therefore the voltage fluctuations in the AC power supply are reduced.

[0193] In one example, two 500W heater elements are placed within the same heater 72. The duty cycle is commanded at 0.125Hz, where the first heater is powered on at t=0 seconds and the second heater is powered on with a 2-second delay. Therefore, the two heater elements cannot be switched on at the same time for any duty cycle. While the two heater elements may be on simultaneously, to reduce current fluctuations, both heaters are preferably not switched on or off simultaneously. In this context, the term "switched on" means the transition from a state where no substantial current flows through the heater element to a state where current flows through the heater element. Figure 155 shows an example of controlling two heater elements at a 25% duty cycle, where the 25% duty cycle is plotted for the first and second heaters. The on / off state of the first heater is plotted by line 12615, and the on / off state of the second heater element is plotted by line 12620 on the time axis against time 12612. The first heater is turned on for 1 second at time marker 12616, and then turned off until time marker 12617, where it is turned on again for a 25% duty cycle. The second heater is turned on at the same duty cycle and frequency, but with a 2-second delay, thereby turning on at time marker 12621. More generally, the second heater operates at the same frequency as the first heater, but with half the period and a delay, where the period is the reciprocal of the frequency. More generally, for n heater elements, numbered from 1 to n and called heater element i, all heater elements operate at the same frequency and duty cycle, but each heater element is delayed by a number obtained by dividing the period by n from the previous heater element i-1. The lower limit for the heater duty cycle command may be zero. The heater may be configured to operate at a 100% duty cycle or a reduced duty cycle. The maximum duty cycle may be limited by the available power. In one embodiment, the maximum duty cycle for the heater may be 70% of a total current consumption of 8 amperes, thereby ensuring that adequate power is maintained to balance the components in the dialysis machine 6001.In another embodiment, the maximum total current consumption is 11 amperes, and the thermal duty cycle is limited to 100%. The user or technician can set the maximum duty cycle of the heater controller and the maximum current consumption of the dialysis machine 6001 (represented in block form in Figure 61) by selecting a high or low power setting via software. The lower power setting allows the dialysis machine 6001 to be plugged into the same circuit as the machine that prepares water for the dialysis machine 6001. The maximum heater command may be limited by the saturation block 619 shown in Figures 123A-123C. The maximum flow rate through the heater can be controlled based on the inlet temperature 254 and available power to produce dialysate that achieves an acceptable minimum dialysate temperature, as measured by sensors 251, 252.

[0194] A heater controller can be considered inherently asymmetrical because it can increase the heater temperature by using more power, but it is affected by heat loss to the ambient air or flowing dialysate, which lowers the heater temperature.

[0195] The temperature in the system can be controlled using two control loops. The first control loop acts on the heater itself, feeding back the internal heater temperature to generate duty cycle commands for the heater. The second control loop causes the controller to loop around the heater loop, calculating the desired heater temperature based on the error between the desired fluid temperature and the actual fluid temperature. The fluid temperature sensor used to provide feedback can be selected based on the desired or selected flow path. The controller can operate in several different modes. The internal loop of the heater can be operated alone to directly control the heater temperature, or the two loops can be operated together to control the fluid temperature.

[0196] The control loop in Figure 123A can be operated with different integral gains 618 and proportional gains 616 to accommodate various levels of heat loss due to external factors, including ambient temperature, incoming dialysate temperature, and dialysate flow rate, but is not limited to these.

[0197] The heater control mode allows for the selection of different gains depending on the operating mode selected in the therapeutic application 6203 (Figure 62). If an operating mode requiring high fluid flow through the heater is selected, gains 616 and 618 can be set higher. If an operating mode requiring low fluid flow through the heater is selected, gains 616 and 618 can be set lower. To prevent temperature overshoot, the gains can be set to the minimum or zero value during modes where there is no flow through the heater. Since the disinfection temperature may be close to the material temperature limit, and large temperature increases associated with thermal disinfection are more likely to cause temperature overshoot, gains 616 and 618 can be set lower during disinfection operation mode to prevent overshoot at high temperatures.

[0198] The saturation block 619 can limit the output 614 of the heater control loop 608 to the output of the maximum heater duty cycle. In a preferred embodiment, the maximum heater duty cycle is selectable between about 70% and about 100%.

[0199] In another embodiment, the value of the integrator 620 can be limited to avoid temperature overshoot. If the heater command is at its upper limit, the value of the integrator 620 cannot be increased until the heater command drops below that upper limit. The value of the integrator can always be decreased.

[0200] To minimize heater temperature fluctuations when the fluid flow through the heater is momentarily stopped, the heater control mode can stop the heater operation and save one or more control parameters to memory. In a preferred embodiment where the fluid flow through the heater is stopped for a short period, the heater can be turned off and the integrator value 620 can be saved. The heater can then be turned on again with gains 616, 618 appropriate for the operating mode and using the integrator value reloaded from memory.

[0201] Figure 123B shows an alternative embodiment of the heater controller called the “fluid temperature control mode”. The fluid temperature control mode can add an external control loop 638 around the internal control loop 608 of the heater control mode. The external control loop 638 can change the actual fluid temperature 632 to the desired fluid temperature 630 by changing the desired heater temperature 610. The fluid temperature control mode supplies this desired heater temperature 610 to the internal control loop 608, which generates a signal 614 to control the heater as described above in the heater control mode. The internal control loop may include changing gains 616, 618 based on the operating mode of the dialysis unit and limiting the integrator when the heater command reaches the maximum allowable value. The fluid temperature control mode may include a feedforward command (ffCmd) 642 based on the following desired temperature 630, inlet fluid temperature 254, fluid flow rate and gain coefficient. ffCmd=T des +(T des -Tin)×m*ffGain In the formula, ffCmd is a feedforward command. T des This is the desired temperature setpoint. T in This is the temperature at the heater inlet. m is the desired mass flow rate. ffGain is the gain applied to the calculation.

[0202] The external control loop 638 may include a saturation block 644 that imposes upper and lower limits on the value between the desired fluid temperature point 630 and the maximum allowable heater temperature for the feedforward command 642. A second saturation block 639 may limit the output 610 of the external control loop 638 to the maximum heater temperature. In a preferred embodiment, the maximum temperature during dialysis may be set to about 70°C and during disinfection to about 112°C.

[0203] The fluid temperature control mode allows for the selection of different gains 636 and 638 depending on the operating mode selected in the therapeutic application 6203 (Figure 62). Gains 636 and 638 can be set higher if the operating mode requires a high fluid flow rate through the heater. Gains 636 and 638 can be set lower if the operating mode requires a low fluid flow rate through the heater 72. To prevent temperature overshoot, the gains can be set to the minimum or zero value when there is no flow through the heater.

[0204] The fluid temperature control mode can limit the integrator value 640 to avoid temperature overshoot. If the heater command 614 or the desired heater temperature 610 is at the maximum allowable value, the integrator value 640 cannot be increased until the heater command and desired heater temperature fall below that upper limit. The integrator value can always be decreased.

[0205] The fluid temperature control mode can optionally vary the dialysate flow rate from the external pump 159 to maintain the dialysate within a desired temperature limit. If the heater command 614 or the desired heater temperature 610 is at its maximum allowable value over a predetermined minimum period, the dialysate flow rate can be reduced to, for example, about 30 ml / min / stroke. If the heater command and the desired heater temperature fall below their upper limits over a predetermined minimum period, the desired flow rate can be increased to, for example, 30 ml / min until the flow rate returns to its original programmed value. In a preferred embodiment, the minimum period is set to the time required to complete the current and subsequent strokes. The fluid temperature control mode uses the minimum period to generate a smoother temperature response and reduce temperature overshoot. The flow through the heater can be limited to a predetermined minimum value. In a preferred embodiment, the minimum flow rate for dialysate through the heater, as measured by the external pump, is set to about 100 ml / min.

[0206] To minimize heater temperature fluctuations when the fluid flow through the heater is briefly stopped, the fluid temperature control mode is programmed to stop heater operation and save one or more control parameters to memory. The dialysis unit may periodically stop the fluid flow to perform functional checks, including dialysate levels and fluid valve performance. In a preferred embodiment where the fluid flow through the heater is briefly stopped, the heater is powered off, while the preceding dialysate flow rate and integrator values ​​640, 620 are saved to memory. When the flow is resumed, the integrator values ​​and dialysate flow rate are reloaded from memory, the heater is powered on again, and the gains 616, 618, 636, 638 are set to be appropriate for the operating mode.

[0207] In an alternative embodiment, as shown in FIG. 123C, the heater controller has a "heater-only output mode" consisting of a control loop 648 around the heater. The heater-only output mode can set the heater temperature 612 to the heater setpoint temperature 610 by using a simple proportional-integral controller to output a duty cycle command to the heater 72. The heater setpoint temperature 610 can be the output of a feedforward command 646 limited by a saturation block 644. The feedforward command 646 can be based on a plurality of parameters such as the measured inlet fluid temperature 647, the desired fluid temperature 611, the assumed fluid mass flow rate, and the gain coefficient. In a preferred embodiment, the feedforward signal 646 can be calculated as follows. ffCmd=T des +(T des -T in )×m A *ffGain Where ffCmd is the feedforward command T des is the desired temperature setpoint T in is the temperature at the inlet of the heater m A is the assumed mass flow rate ffGain is the gain applied to the calculation.

[0208] The feedforward command 646 can be limited to any value by the saturation block 644. In a preferred embodiment, the saturation block 644 limits the desired heater temperature 610 to a value between the desired fluid temperature 611 and a maximum value, such as 41°C.

[0209] The heater temperature 612 can be measured by a heater temperature sensor. The inlet temperature is measured by sensor 254. The duty cycle command can be converted to a PWM command, which in one embodiment has a fundamental frequency of approximately 1 Hz. The heater current can be controlled by the PWM command using an SCR electronic circuit or a transistor switch such as an FET, IGBT, or BJT that turns on and off at zero crossing. Assuming a power supply frequency of 60 Hz, a 1 Hz PWM frequency allows for a resolution of 1 / 60.

[0210] The lower limit for the heater duty cycle command can be set to zero. The heater can be configured to operate at a 100% duty cycle or a reduced duty cycle. The maximum duty cycle may be limited by the available power. In a preferred embodiment, the maximum duty cycle is set to approximately 70%, limiting the total power consumption to 8 amperes, which allows for an output that maintains balance among the components in the dialysis machine 6001. Alternatively, the maximum total current consumption is set to 11 amperes, limiting the thermal duty cycle to 100%. The user or technician can set the maximum duty cycle of the heater controller and the maximum current consumption of the dialysis machine 6001 by selecting a high-power or low-power setting via software. The lower power setting allows the dialysis machine 6001 to be plugged into the same circuit as the machine that prepares the water for the dialysis machine 6001. Depending on the available power, the maximum flow rate through the heater can be controlled by monitoring the inlet temperature 254 so that the dialysate produced reaches an acceptable minimum dialysate temperature, as measured by sensors 251, 252.

[0211] The heater-only output mode allows for the selection of different gains depending on the operating mode selected in the therapeutic application 6203 (Figure 62). If an operating mode requiring a high fluid flow rate through the heater is selected, gains 616 and 618 can be set higher. If an operating mode requiring a low fluid flow rate through the heater is selected, gains 616 and 618 can be set lower. To prevent temperature overshoot, the gains can be set to the minimum or zero value during modes where there is no flow through the heater. Since the disinfection temperature may approach the material temperature limit, and a large temperature rise is more likely to cause temperature overshoot, gains 616 and 618 can be set lower during disinfection operation mode to prevent overshoot at high temperatures.

[0212] Another way to avoid temperature overshoot involves limiting the integrator value to 620. If the heater command is that upper limit, the integrator value cannot be increased until the heater command drops below that upper limit. The integrator value can always be decreased.

[0213] To minimize heater temperature fluctuations when the fluid flow through the heater momentarily stops, the heater-only output mode can stop heater operation and save one or more control parameters to memory. In a preferred embodiment where the fluid flow through the heater is stopped for a short period, the heater can be powered off and the integrator value 620 can be saved. The heater can then be powered on again by reloading the integrator value from memory with gains 616, 618 set to be appropriate for the operating mode.

[0214] In one embodiment of the heater controller, several safety checks are performed during startup to verify the functionality of the heater system, which includes the heater function, temperature sensor, and control electronics. The startup safety checks may include verifying that the temperature sensor output is within the expected range. In this embodiment, the expected range for the temperature sensor is 0°C to 110°C.

[0215] To verify that the heater can be powered on and off, a start-up safety check may include a heater system test in which the heater is powered on for a short period and the heater temperature sensor is monitored during this power-on period and thereafter during the power-off period. The test may require that the heater sensor value increases during the power-on period and does not continue to increase during the power-off period. In a preferred embodiment using a single heater element, the heater is powered on for about 5 seconds and the temperature sensor is monitored during the 5-second power-on period and the subsequent 20-second power-off period. In the embodiment, the test is passed if the heater temperature rises by at least about 1.0°C and about 6.0°C or more.

[0216] A safety check of multiple heater elements verifies the functionality of each heater element and its associated control switch. The safety check can be performed on one element at a time, monitoring the heater temperature while switching it on for a period of time and then off. This process is repeated for each heater element, thereby verifying that each element and its control switch are operational. To pass the safety check, the monitored temperature must rise above a first predetermined value while the heater element is powered on, and thereafter, during the power-off period, it must not rise above a second predetermined threshold. In one example, the safety check also requires that the temperature does not rise above a third predetermined threshold during the power-on period.

[0217] In a preferred embodiment having two heater elements, the first heater element or preheater element is located in the heater body on the tip side from the temperature sensor. The safety check involves powering on the preheater for 15 seconds on a 100% duty cycle, followed by a 45-second off period, during which the temperature rise is measured over a 60-second period. The temperature rise is monitored throughout the test period. At any point, if the heater temperature rise exceeds 6 degrees, the heater is powered off and the test fails. At the end of the 60 seconds, the heater temperature rise must be at least 0.5 degrees to pass the test. The safety check of the second heater element involves powering on the second heater element for approximately 5 seconds on a 100% duty cycle, during which the temperature sensor is monitored over the 5-second on period and the subsequent 20-second off period. In the embodiment, the test passes if the heater temperature rises by at least approximately 1.0°C and at least approximately 6.0°C.

[0218] During operation of the dialysis unit, the heater temperature is monitored when the heater command 614 is at its maximum value to verify proper heater function. To pass this test, the heater temperature is expected to rise by a predetermined amount over a specified period. In a preferred embodiment, the heater temperature is expected to rise by more than approximately 0.5°C over one minute. This test can be performed during an operating mode in which the patient is connected to the dialysis unit.

[0219] Safety testing allows monitoring of the heater temperature during all operations to avoid excessive fluid temperatures. If the heater temperature 612 exceeds the maximum allowable heater temperature for a given operating mode, the heater and heater controller become unusable. In a preferred embodiment, the maximum heater temperature during patient connection operation is set to approximately 70°C. The maximum heater temperature during disinfection mode can be set to a higher temperature, such as approximately 100°C to 110°C. The heater may include a secondary safety system consisting of a heater thermal fuse.

[0220] The safety test monitors two or more of the fluid temperature sensors, and if any one of the temperature sensors exceeds the maximum disinfection fluid temperature, the heater 14 and heater controller can be disabled. Preferably, all of the fluid temperature sensors 251, 252, 254, and 255 are monitored, and the maximum disinfection fluid temperature is set to approximately 100°C. One advantage of this test is that it provides protection against failure of a single fluid temperature sensor or a heater temperature sensor.

[0221] Safety testing may include monitoring the external pump 157 during fluid temperature control mode and disabling the heater 72 and heater controller if fluid flow cannot be verified. If the external pump controller detects blockage or air leakage, the heater 72 and controller may be disabled in fluid temperature control mode.

[0222] The heater control unit described above is merely an example, and it should be understood that other heater control systems and other heaters are also possible in other embodiments of the present invention. The dialysate can also be filtered to remove contaminants, infectious organisms, pathogens, pyrogens, residues, etc., for example using an ultrafiltration device. The filter can be placed at any suitable position in the dialysate flow path, for example, between the directional circuit and the equilibrium circuit, as shown in Figure 3A, and / or the ultrafiltration device can be incorporated into the directional circuit or the equilibrium circuit. When an ultrafiltration device is used, it can be selected to have a mesh or pore size that is chosen so that the species described above do not pass through the filter. For example, the mesh or pore size may 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. Those skilled in the art are familiar with filters such as ultrafiltration devices, and in many cases such filters can be readily available commercially.

[0223] In some cases, the ultrafiltration system can be operated so that waste from the filter (e.g., concentrated water flow) is passed to a waste flow, such as the waste line 39 in Figure 6. In some cases, the amount of dialysate flowing into the concentrated water flow can be controlled. For example, if the concentrated water is too cold (i.e., the heater 72 is not working, or the heater 72 has not heated the dialysate to a sufficient temperature), the entire dialysate flow (or at least a portion of the dialysate) can be diverted to the waste line 39 and optionally recirculated to the dialysate tank 169 using line 48. The flow from the filter can also be monitored for several reasons, for example, using temperature sensors (e.g., sensors 251 and 252), conductivity sensors (e.g., sensor 263 to check the dialysate concentration), etc. Examples of such sensors will be discussed later. Further non-limiting examples are provided in U.S. Patent Application No. 12 / 038,474, filed on 27 February 2008 and incorporated herein by reference, “Sensor Apparatus Systems, Devices and Methods.”

[0224] In this particular example, it should be noted that the ultrafiltration and dialysis machines provide redundant sorting methods for removing contaminants, infectious organisms, pathogens, pyrogens, and residues (although in other cases, the ultrafiltration machine may not be present). Therefore, for contaminants to reach the patient from the dialysate, they must pass through both the ultrafiltration and dialysis machines. Even if one fails to filter, the other can still enable sterilization and prevent contaminants from reaching the patient's blood.

[0225] The directional circuit 142 may also direct the used dialysate coming from the equilibrium circuit to a drain, for example, through the waste line 39 in Figure 6 to drain 31. The drain may be, for example, a localized drain or a separate container for containing waste (e.g., used dialysate) to be properly disposed of. In some cases, one or more check valves or "one-way" valves (e.g., check valves 215 and 216) may be used to control the flow of waste from the directional circuit and from the system. In some cases, a blood leak sensor (e.g., sensor 258) may be used to determine whether blood is leaking through the dialysate flow path through the dialyzer. Furthermore, a liquid sensor may be placed in the collection pan at the bottom of the hemodialysis unit to indicate leaks of blood, dialysate, or both from either of the fluid circuits.

[0226] The drain 31 (Figure 89) may include an air-in-line (AIL) detector 37 that monitors the balancing and directional circuits for leaks and stubble ruptures. The dialysate flowing beyond the AIL detector 37 has previously flowed through several valves with the pumps in the directional cassette and balancing chamber and the pump in the balancing cassette. If either the valve or the stubble of the pod pump leaks, the leaked air flows through the AIL detector in the drain 31. Furthermore, the AIL detector 37 can detect gases generated from the dialysate, which may be heated. In a preferred embodiment, the AIL detector 37 is located in the drain 31 when the flow is upward. This potentially advantageous position facilitates the detection of bubbles flowing with the dialysate, as it provides sufficient opportunity for the drain path (which can be lengthwise to a suitable degree) to solidify before the bubbles reach the detector 37. By positioning the AIL detector 37 in the drain 31, the detector can identify stubble ruptures from bubbles.

[0227] Furthermore, the directional circuit 142 can receive water from a water supply unit 30, for example, a water container such as a bag, and / or from a device capable of generating water, such as a commercially available reverse osmosis device. In some cases, as is known to those skilled in the art, the water entering the system is set to a certain purity, for example, having an ion concentration below a certain value. The water entering the directional circuit 142 can be passed to various locations, for example, to a mixing circuit to generate fresh dialysate and / or to a waste line 39. In some cases, as will be described later, a conduit 67 can be connected between the directional circuit 142 and the blood flow circuit 141 so that a valve to a drain 31, various recirculation lines can be opened and water can flow continuously through the system. If a heater 72 is also driven, the water passing through the system is continuously heated to a temperature sufficient to disinfect the system, for example. Such disinfection methods will be described in detail later.

[0228] Figures 41–45 show non-limiting examples of equilibrium cassettes. Referring here to Figures 41A and 41B, the outside of the top plate 900 of one embodiment of the cassette is shown. The top plate 900 includes one half of the pod pumps 820, 828. This half is the fluid / liquid half through which the source fluid flows. Inlet and outlet pod pump fluid passages are shown. These fluid passages lead to their respective pod pumps 820, 828.

[0229] Pod pumps 820, 828 may include raised channels 908, 910. The raised channels 908, 910 allow fluid to continue flowing through the pod pumps 820, 828 after a partition (not shown) has reached the end of its stroke. Thus, the raised channels 908, 910 minimize the partition trapping air or fluid in the pod pumps 820, 828, or blocking the inlet or outlet of the pod pumps 820, 828 (thereby blocking the flow). In this embodiment, the raised channels 908, 910 are shown to have specific dimensions. In alternative embodiments, the raised channels 908, 910 may be wider or narrower, or in yet another embodiment, the raised channels 908, 910 may be of any dimensions, since the purpose is to control the fluid flow to achieve a desired flow rate or behavior of the fluid. Therefore, the dimensions shown and described herein for raised flow channels, pod pumps, valves or any other embodiments are merely illustrative alternative embodiments. Other embodiments are readily apparent. Figures 41C and 41D show the inside of the top plate 900 of this embodiment of the cassette. Figure 41E shows a side view of the top plate 900.

[0230] Referring here to Figures 42A and 42B, the liquid / fluid side of the intermediate plate 1000 is shown. Figures 41C and 41D show regions complementary to the flow path of the inner top plate. These regions are slightly raised trajectories, indicating a surface finish that contributes to laser welding, one mode of manufacturing in this embodiment. Other modes of manufacturing the cassette are described above.

[0231] Next, referring to Figures 42C and 42D, the air side of the intermediate plate 1000 in this embodiment is shown, or the side facing the bottom plate (not shown, shown in Figures 43A to 43E). The air side of valve holes 802, 808, 814, 816, 822, 836, 838, 840, 842, 844, and 856 corresponds to the fluid side holes of the intermediate plate 1000 (shown in Figures 42A and 42B). As shown in Figures 44C and 44D, partition wall 1220 completes the pod pumps 820 and 828, and partition wall 1222 completes the valves 802, 808, 814, 816, 822, 836, 838, 840, 842, 844, and 856. Valves 802, 808, 814, 816, 822, 836, 838, 840, 842, 844, and 856 are pneumatically driven, and when the bulkhead is pulled away from the hole, liquid / fluid can flow. When the bulkhead is pushed toward the hole, the liquid flow is blocked. The fluid flow is directed by the opening and closing of valves 802, 808, 814, 816, 822, 836, 838, 840, 842, 844, and 856. Next, referring to Figures 43A and 43B, the interior of the bottom plate 1100 is shown. The interior of the operating / air chamber of pod pumps 820, 828 and valves 802, 808, 814, 816, 822, 836, 838, 840, 842, 844, and 856 is shown. The pod pumps 820, 828 and valves 802, 808, 814, 816, 822, 836, 838, 840, 842, 844, and 856 are driven by a pneumatic air source. Referring here to Figures 43C and 43D, the outside of the bottom plate 1100 is shown. The air supply source is mounted on this side of the cassette. In one embodiment, a tube connects to the valves and the tube above the pump 1102. In some embodiments, the valves are interlocked, and two or more valves are driven by the same air line.

[0232] Referring here to Figures 44A and 44B, the assembled cassette 1200 is shown. Figures 12C and 12D show exploded views of the assembled cassette 1200 shown in Figures 44A and 44B. These figures show embodiments of the pod pump bulkhead 1220. The bulkhead gasket provides a seal between the liquid chamber (of the top plate 900) and the air / operating chamber (of the bottom plate 1100). In some embodiments, the dome-shaped irregularities of the bulkhead 1220 provide additional space for air and liquid to leak out of the chamber, particularly at the end of the stroke. In alternative embodiments of the cassette, the bulkhead may include a double gasket. The double gasket feature is preferred in embodiments where both sides of the pod pump contain liquid, or in applications where sealing the sides of both chambers is desired. In these embodiments, a rim complementary to the gasket or other feature (not shown) is added to the inner bottom plate 1100 so that the gasket seals the pod pump chamber of the bottom plate 1100.

[0233] Referring now to Figure 45, a cross-sectional view of the cassette pod pump 828 is shown. This figure shows details of the mounting fixture for the partition wall 1220. In this embodiment as well, the partition wall 1220 gasket is clamped between the intermediate plate 1000 and the bottom plate 1100. The rim of the intermediate plate 1000 provides a feature for the gasket to seal the pod pump 828 chamber located on the top plate 900.

[0234] Next, referring to Figure 45, this cross-sectional view shows valves 834 and 836 in the assembled cassette. Partition wall 1220 is shown assembled and in this embodiment is held in place by being sandwiched between the intermediate plate 1000 and the bottom plate 1100. Still referring to Figure 45, this cross-sectional view also shows valve 822 in the assembled cassette. Partition wall 1222 is shown to be held in place by being sandwiched between the intermediate plate 1000 and the bottom plate 1100.

[0235] In one embodiment, the dialysate can be prepared separately and introduced into the system for use in the directional circuit. However, in some cases, the dialysate can be prepared within the mixing circuit. The mixing circuit can be operated to produce the dialysate at any suitable time. For example, the dialysate can be produced during and / or before the patient's dialysis (the dialysate can be stored, for example, in a dialysate tank). Within the mixing circuit, water (for example, from a water supply unit, optionally delivered to the mixing circuit by the directional circuit) can be mixed with various dialysate raw materials to form the dialysate. Those skilled in the art are known of suitable dialysate raw materials, such as sodium bicarbonate, sodium chloride, and / or acids, as described above. The dialysate can be prepared as needed, so that it does not need to be stored in large quantities, although in some cases some can be stored in a dialysate tank.

[0236] Figure 7A shows a non-limiting example of a mixing circuit that may be incorporated into a cassette. In Figure 7A, water from the directional circuit flows into the mixing circuit 25 by the action of pump 180. In some cases, a portion of the water is directed to a raw material 49 used, for example, to transport the raw material through the mixing circuit. As shown in Figure 7A, water is delivered to a bicarbonate source 28 (which may also contain sodium chloride). In some cases, sodium chloride and / or bicarbonate may be provided in powder or granular form that is moved by the action of water. The bicarbonate from the bicarbonate source 28 is fed into the mixing line 186 via bicarbonate pump 183, into which water from the directional circuit also flows. Acid from acid source 29 (which may be in liquid form) is also fed into the mixing line 186 by acid pump 184. The raw materials (water, bicarbonate, acid, NaCl, etc.) are mixed in the mixing chamber 189 to produce dialysate, which then flows out of the mixing circuit 25. Conductivity sensors 178 and 179 are positioned along the mixing line 186 to ensure that each raw material is added at the appropriate concentration as it is added to the mixing line. This method and its control, which ensure that an acceptable dialysate quality is produced and maintained during treatment, will be described in more detail later.

[0237] In one embodiment, pump 180 comprises one or more pod pumps similar to those described above. The pod pump may include a rigid chamber, the rigid chamber having a flexible partition dividing each chamber into a fluid compartment and a control compartment. The control compartment may be connected to a control fluid source, such as an air source. Non-limiting examples of pumps that can be used as pod pumps are described in U.S. Provisional Patent Application No. 60 / 792,073, filed April 14, 2006, entitled "Extracorporeal Thermal Therapy Systems and Methods," or in U.S. Patent Application No. 11 / 787,212, filed April 13, 2007, entitled "Fluid Pumping Systems, Devices and Methods," each incorporated herein by reference. Similarly, in some cases, pumps 183 and / or 184 may each be pod pumps. Further details of the pod pumps are described below.

[0238] In some cases, one or more of the pumps may have a pressure sensor that monitors the pressure inside the pump. This pressure sensor can be used to ensure that the pump compartment is fully filled and discharged. For example, ensuring that the pump discharges a full stroke of fluid can be done by (i) filling the compartment, (ii) closing both fluid valves, (iii) pressurizing the compartment by opening the valve between the positive pneumatic reservoir and the compartment, (iv) closing this positive pressure valve to leave pressurized air in the passage between the valve and the compartment, (v) opening the fluid valve so that the fluid can exit the pump compartment, and (vi) monitoring the pressure drop in the compartment as the fluid exits. The pressure drop corresponding to a full stroke can be consistent and may be determined by the initial pressure, the hold-up capacity between the valve and the compartment, and / or the stroke capacity. However, in any other embodiment of the pod pumps described herein, a reference capacity compartment may be used, and this capacity is determined through pressure and capacity data.

[0239] The volume discharged by a water pump and / or other pumps can be directly correlated to conductivity measurements, and thus the volume measurements can be used as a cross-check for the composition of the dialysate produced. This ensures that the dialysate composition remains safe even if conductivity measurements become inaccurate during treatment.

[0240] Figure 7B is a schematic diagram showing another example of a mixing circuit that may be incorporated into a cassette. The mixing circuit 25 in this figure includes a pod pump 181 that delivers water from a water supply unit along line 186, into which various raw materials for creating dialysate are introduced. Another pump 182 delivers water from the water supply unit into a supply source 28 (e.g., a container) holding sodium bicarbonate and / or into a supply source 188 holding sodium chloride. A third pump 183 introduces dissolved bicarbonate into the mixing line 186 (mixed in a mixing chamber 189), and a fourth pump introduces dissolved sodium chloride into line 186 (mixed in a mixing chamber 191). A fifth pump 184 introduces acid into the water before it passes through the first pump 181. Mixing is monitored using conductivity sensors 178, 179, and 177, each measuring conductivity after a given raw material has been added to the mixing line 186, to ensure that the appropriate amount and / or concentration of raw material is being added. Examples of such sensors will be discussed later. Further non-limiting examples are provided in U.S. Patent Application No. 12 / 038,474, filed on 27 February 2008 and incorporated herein by reference, “Sensor Apparatus Systems, Devices and Methods.” The method and its control for ensuring that acceptable dialysate quality is generated and maintained during treatment will be discussed in more detail later.

[0241] Referring now to Figure 3B, in this embodiment, the mixing circuit 25 constitutes the dialysate using two sources, namely the acid stock source 27 and the combined sodium bicarbonate (NaHCO3) and sodium chloride (NaCl) sources. As shown in the embodiment in Figure 3B, in some embodiments, the dialysate constituting system 25 may include multiples of each source. In embodiments in which the system is operated continuously, redundant dialysate sources enable the continuous functioning of the system because one set of sources is exhausted, the system uses the redundant sources, and the first set of sources is replaced. This process is repeated as needed, for example, until the system is shut down.

[0242] Figures 34 to 36 show non-limiting examples of equilibrium cassettes. In the exemplary fluid flow cassette shown in Figure 37, the valves open independently. In this exemplary embodiment, the valves open pneumatically. In this embodiment, they are volcano valves, as described in more detail elsewhere in this specification.

[0243] Referring here to Figures 38A and 38B, the top plate 1100 of one exemplary embodiment of the cassette is shown. In this exemplary embodiment, the pod pumps 820, 828 and the mixing chamber 818 on the top plate 1100 are formed similarly. In this exemplary embodiment, the pod pumps 820, 828 and the mixing chamber 818, when assembled with the bottom plate, have a total capacity of 38 ml. However, in other embodiments, the mixing chamber may have a capacity of any desired size.

[0244] Referring here to Figure 38B, a bottom view of the top plate 1100 is shown. This figure shows the fluid channels. These fluid channels correspond to the fluid channels shown in Figures 39A to 39B in the intermediate plate 1200. The tops of the top plate 1100 and the intermediate plate 1200 form the liquid or fluid side of the cassette for the pod pumps 820, 828 and for one side of the mixing chamber 818. Thus, the majority of the liquid flow channels are located in the top plate 1100 and the intermediate plate 1200. Referring to Figure 39B, the first fluid inlet 810 and the first fluid outlet 824 are shown.

[0245] Still referring to Figures 38A and 38B, the pod pumps 820, 828 include a groove 1002 (in alternative embodiments, this is the groove). While the groove 1002 is shown to be of a specific size and shape, in other embodiments, the size and shape of the groove 1002 can be any desired size or shape. The size and shape shown in Figures 38A and 38B is one exemplary embodiment. In all embodiments of the groove 1002, the groove 1002 forms a passage between the fluid inlet side and the fluid outlet side of the pod pumps 820, 828. In alternative embodiments, the groove 1002 is a groove in the wall of the internal pumping chamber of the pod pump.

[0246] The groove 1002 provides a fluid passage so that when the partition is at the end of the stroke, there is still a fluid passage between the inlet and outlet, thereby preventing a pocket of fluid or air from being trapped in the pod pump. The groove 1002 is included on both the liquid / fluid side and the air / actuating side of the pod pumps 820, 828. In some embodiments, the groove 1002 can also be included in the mixing chamber 818 (see Figures 40A-40B with respect to the operating / air side of the pod pumps 820, 828 and the opposite side of the mixing chamber 818). In alternative embodiments, the groove 1002 is either not included at all or is included on only one side of the pod pumps 820, 828.

[0247] In alternative embodiments of the cassette, the liquid / fluid side of the pod pumps 820, 828 may include features (not shown) in which the inlet and outlet flow paths are continuous, and a rigid outer ring (not shown) molded around the pumping chamber is also continuous. This feature allows for the maintenance of a seal formed together with a partition (not shown). Referring to Figure 38E, a side view of an exemplary embodiment of the top plate 1100 is shown.

[0248] Referring here to Figures 39A to 39B, exemplary embodiments of the intermediate plate 1200 are shown. The intermediate plate 1200 is also shown in Figures 37A to 37F, which correspond to Figures 39A to 39B. Thus, Figures 37A to 37F show the locations of various valves and passages. The location of the mixing chamber 818 is shown, along with the location of the partitions (not shown) for the respective pod pumps 820 and 828.

[0249] Referring here to Figure 39A, in one exemplary embodiment of the cassette, sensor elements are incorporated into the cassette to identify various characteristics of the fluid being dispensed. In one embodiment, three sensor elements are included. However, in this embodiment, six sensor elements (two sets of three) are included. The sensor elements are located in sensor cells 1314, 1316. In this embodiment, sensor cells 1314, 1316 are included as areas of the cassette for the sensor elements. In one embodiment, three sensor elements from two sensor cells 1314, 1316 are housed in respective sensor element housings 1308, 1310, 1312 and 1318, 1320, 1322. In one embodiment, two of the sensor element housings 1308, 1312 and 1318, 1320 house conductivity sensor elements, and the third sensor element housing 1310, 1322 houses temperature sensor elements. Conductivity sensor elements and temperature sensor elements can be any conductivity sensor element or temperature sensor element in the art. In one embodiment, the conductivity sensor element is a graphite post. In other embodiments, the conductivity sensor element is a post made of stainless steel, titanium, platinum, or any other metal that is coated to be corrosion-resistant but still conductive. The conductivity sensor element includes electrical leads that transmit probe information to a controller or other device. In one embodiment, the temperature sensor is a thermistor embedded in a stainless steel probe. However, alternative embodiments use combinations of temperature sensor elements and conductivity sensor elements similar to those described in the U.S. Patent Application (DEKA-024XX) filed October 12, 2007, entitled "Sensor Apparatus Systems, Devices and Methods".

[0250] In alternative embodiments, the cassette may have no sensors, or only a temperature sensor, or only one or more conductivity sensors, or one or more of other types of sensors.

[0251] Referring here to Figure 39C, a side view of an exemplary embodiment of the intermediate plate 1200 is shown. Referring here to Figures 40A and 40B, the bottom plate 1300 is shown. Referring first to Figure 40A, the inner surface or inner side of the bottom plate 1300 is shown. The inner surface or inner side is the side that contacts the bottom surface of the intermediate plate (not shown). The bottom plate 1300 is attached to air or an operating line (not shown). Corresponding inlet holes of the intermediate plate 1300 for air to operate the pod pumps 820, 828 and valves (not shown, see Figures 37A to 37F) are shown. Holes 810 and 824 correspond to the first fluid inlet and first fluid outlet shown in Figures 39B, 810, and 824, respectively. Corresponding halves of the pod pumps 820, 828 and mixing chamber 818 are also shown, as well as grooves 1002 for the fluid passages. The operating holes of the pumps are also shown. Unlike the top plate, the corresponding halves of the bottom plate 1300 for the pod pumps 820, 828 and the mixing chamber 818 highlight the differences between the pod pumps 820, 828 and the mixing chamber 818. The pod pumps 820, 828 include an air / operating passage in the bottom plate 1300, while the mixing chamber 818 has the same structure as the halves in the top plate. The mixing chamber 818 mixes liquids and therefore does not include a partition (not shown) or an air / operating passage. Sensor cells 1314, 1316 with three sensor element housings 1308, 1310, 1312 and 1318, 1320, 1322 are also shown.

[0252] Referring here to Figure 40B, an actuation port 1306 is shown on the outer or external bottom plate 1300. An actuation source is connected to these actuation ports 1306. In this case as well, the mixing chamber 818 does not have an actuation port because it is not driven by air. Referring here to Figure 40C, a side view of an exemplary embodiment of the bottom plate 1300 is shown.

[0253] As described above, in various aspects of the present invention, one or more fluid circuits, such as blood flow circuits, equilibrium circuits, directional circuits, and / or mixing circuits, can be implemented in the cassette. Other cassettes may exist, such as a sensing cassette disclosed in U.S. Patent Application No. 12 / 038,474, filed on February 27, 2008, and incorporated herein by reference. In some embodiments, some or all of these circuits are combined in a single cassette. In alternative embodiments, each of these circuits is defined in its own cassette. In yet another embodiment, one cassette contains two or more of the fluid circuits. In some cases, two, three or more cassettes can be fixed to each other, with fluid connections between the cassettes as optional. For example, in one embodiment, two cassettes can be connected via a pump, such as a pod pump as described above. The pod pump may include a rigid chamber, which is provided with a flexible partition dividing each chamber into a first side and a second side, which can be used for the various purposes described above.

[0254] Non-limiting examples of cassettes that can be used in the present invention include U.S. Patent Application No. 11 / 871,680, titled "Pumping Cassette," filed on October 12, 2007; U.S. Patent Application No. 11 / 871,712, titled "Pumping Cassette," filed on October 12, 2007; U.S. Patent Application No. 11 / 871,787, titled "Pumping Cassette," filed on October 12, 2007; U.S. Patent Application No. 11 / 871,793, titled "Pumping Cassette," filed on October 12, 2007; and "Cassette System Integrated Examples include those described in U.S. Patent Application No. 11 / 871,803, entitled “Apparatus,” or U.S. Patent Application No. 12 / 035,648, entitled “Cassette System Integrated Apparatus,” filed on 27 February 2008. Each of these is incorporated herein by reference as a whole.

[0255] The cassette may also include various features such as pod pumps, fluid lines, and valves. The cassette embodiments shown and described herein include exemplary and various alternative embodiments. However, any variety of cassettes with similar functionality are contemplated. The cassette embodiments described herein are implementations of fluid circuit diagrams as shown in the figures, but in other embodiments, the cassette may have various arrangements of fluid lines and / or valves and / or arrangements and numbers of pod pumps, and therefore remain within the scope of the present invention.

[0256] In one exemplary embodiment, the cassette may include a top plate, an intermediate plate, and a bottom plate. Various embodiments exist for each plate. Generally, the top plate includes the pump chamber and fluid lines, the intermediate plate includes complementary fluid lines, a metering pump, and valves, and the bottom plate includes the working chamber (in some embodiments, the top and bottom plates include complementary parts of the balancing chamber or pod pump).

[0257] Generally, the partition wall is located between the intermediate plate and the bottom plate, but with respect to the equilibrium chamber or pod pump, a portion of the partition wall is located between the intermediate plate and the top plate. Some embodiments include cases where the partition wall is attached to the cassette by overmolding, capture, bonding, press-fitting, welding, or any other mounting process or method, but in exemplary embodiments, the partition wall is separate from the top plate, intermediate plate, and bottom plate until the plates are assembled.

[0258] The cassette can be constructed from a variety of materials. Generally, in various embodiments, the materials used are solid and non-flexible. In one embodiment, the plate is made of polysulfone, while in other embodiments, the cassette is made from any other solid material, and in exemplary embodiments, from any thermoplastic or thermosetting material.

[0259] In one exemplary embodiment, the cassette is formed by positioning the partitions in their correct positions (for example, relative to one or more pod pumps, if present), assembling the plates in sequence, and connecting the plates. In one embodiment, the plates are connected using a laser welding technique. However, in other embodiments, the plates may be bonded, mechanically fastened, tied together, ultrasonically welded, or any other mode of joining the plates together.

[0260] In practice, cassettes can be used to deliver any type of fluid from any source to any location. Types of fluids include nutrient-rich fluids, non-nutrient-rich fluids, inorganic chemicals, organic chemicals, bodily fluids, or any other type of fluid. Furthermore, in some embodiments, the fluid includes gases, and therefore, in some embodiments, gases are delivered using cassettes.

[0261] The cassette serves to deliver and direct the fluid from and to a desired location. In some embodiments, an external pump pumps the fluid into the cassette, and the cassette pumps the fluid out. However, in some embodiments, a pod pump pumps the fluid into the cassette and pumps the fluid out of the cassette.

[0262] As described above, the fluid pathway is controlled according to the valve's position. Therefore, valves in different positions or additional valves constitute alternative embodiments of this cassette. Furthermore, the fluid lines and pathways shown in the figure above are merely examples of fluid lines and pathways. Other embodiments may have more, fewer, and / or different fluid pathways. In yet another embodiment, there are no valves in the cassette.

[0263] The number of pod pumps (if there are pod pumps in the cassette) can also be varied depending on the embodiment. For example, the various embodiments shown and described above include two pod pumps, while in other embodiments the cassette includes one pod pump. In yet another embodiment, the cassette may include three or more pod pumps, or there may be no pod pumps at all. The pod pump may be a single pump, or there may be multiple pod pumps that can act in tandem, for example, to provide a more continuous flow, as described above. Either or both can be used in the various embodiments of the cassette. However, as described above, in some cases there may be no pod pumps in the cassette, but they may be housed between two or more cassettes. A non-limiting example of such a system is shown in U.S. Patent Application No. 12 / 038,648, entitled "Cassette System Integrated Apparatus," filed on 27 February 2008 and incorporated herein by reference.

[0264] The various fluid inlets and outlets disclosed herein may, in some cases, be fluid ports. In practice, depending on the arrangement and control of the valves, a fluid inlet may also be a fluid outlet. Therefore, referring to a fluid port as either a fluid inlet or a fluid outlet is merely for illustrative purposes. Various embodiments have interchangeable fluid ports. Fluid ports are provided to give the cassette a specific fluid path. Not all of these fluid ports are necessarily used at all times; rather, the variety of fluid ports actually provides flexibility in the use of the cassette.

[0265] Referring to Figure 46, another non-limiting example of a cassette is shown. Referring here to Figure 46A, an integrated, assembled cassette system is shown. The mixing cassette 500, intermediate cassette 600, and balancing cassette 700 are connected by fluid lines or conduits. The pods are located between the cassettes. Referring here to Figures 46B and 46C, various diagrams illustrate the efficiency of the integrated cassette system. Referring here to Figures 50A, 50B, and 50C, fluid lines or conduits 1200, 1300, and 1400 are shown, respectively. The fluid flows between the cassettes through these fluid lines or conduits. Referring here to Figures 50A and 50B, these fluid lines or conduits represent the larger check valve fluid line 1300 and the smaller check valve fluid line 1200. In the exemplary embodiment, the check valves are duckbill valves, but in other embodiments, any check valves may be used. Referring to Figure 50C, the fluid line or conduit 1400 is a fluid line or conduit that does not contain a check valve. For the purposes of this explanation, the terms “fluid line” and “conduit” are used synonymously with respect to 1200, 1300 and 1400.

[0266] Referring here to Figures 46B, 46C and 51A, the following is a description of one embodiment of fluid flow through various cassettes. For ease of explanation, the fluid flow starts at mixing cassette 500. Referring here to Figures 46B and 51A, the fluid side of mixing cassette 500 is shown. The fluid side includes a plurality of ports 8000, 8002, 8004, 8006, 8008 and 8010-8026, which are either fluid inlets or fluid outlets. In various embodiments, the fluid inlets and outlets may include one or more fluid inlets for reverse osmosis ("RO") water 8004, bicarbonate, acid and dialysate 8006. Also, one or more fluid outlets including drain, acid 8002 and at least one air vent outlet as an exhaust port for the dialysate tank. In one embodiment, a tube (not shown) is located behind the outlet and is an exhaust port (to prevent contamination). Additional outlets are also included for water, bicarbonate and water mixtures, and dialysate mixtures (bicarbonate with added acid and water).

[0267] The dialysate flows from the mixing cassette 500 to the dialysate tank (not shown, indicated as 1502 in Figure 51A), and then through the conduit to the internal dialysate cassette 700 (feeded by pod pumps 602 and 604 of the external dialysate cassette 600 (604 not shown, shown in Figures 46D and 46E)). The fluid paths within the cassettes can be modified. Thus, various inlet and outlet positions can be changed along with various cassette fluid paths.

[0268] Referring here to Figure 51B, in one embodiment of the cassette system, a chondrocyte, a conductivity sensor, and a temperature sensor are contained in a separate outer cassette 1504 of the cassette system shown in Figures 46A to 46C. This outer sensor cassette 1504 may be one of those described in U.S. Patent Application No. 12 / 038,474, filed on 27 February 2008 and incorporated herein by reference, “Sensor Apparatus Systems, Devices and Methods.”

[0269] Figure 51B shows the fluid flow path for this embodiment. In this embodiment, during the mixing process for the dialysate, the bicarbonate mixture flows away from the mixing cassette 500 to the outer sensor cassette and then flows back into the mixing cassette 500. When the bicarbonate mixture meets a pre-established threshold, acid is added to the bicarbonate mixture. Next, as the bicarbonate and acid are added in the mixing chamber 506, the dialysate flows out of the cassette to the sensor cassette and then back into the mixing cassette 500. This method and its control, which ensure that an acceptable dialysate quality is produced and maintained during treatment, will be described in more detail later.

[0270] Referring here to Figure 46D, the mixing cassette 500 includes a pneumatically operated side. In the block shown as 500, the cassette 500 incorporates several valves and two pumping chambers 8030, 8032 for dispensing or metering the acid or bicarbonate. In some embodiments, additional or fewer metering pumps are included. The metering pumps 8030, 8032 can be of any desired size. In some embodiments, the pumps are different sizes relative to each other, while in other embodiments, the pumps are the same size relative to each other. For example, in one embodiment, the acid pump is smaller than the bicarbonate pump. This may be more efficient and effective when using higher concentrations of acid, as it may be desirable to use a smaller pump for accuracy, and also because, for control schemes, it may be desirable to have a smaller pump to use a full stroke rather than a partial stroke in the control.

[0271] Conduits 1200 and 1300 include check valves. These conduits 1200 and 1300 allow for unidirectional flow. In an exemplary embodiment, all of these conduits 1200 and 1300 lead to a drain. Referring to the flow path circuit diagram in Figure 51A, the location of these check valve conduits is clear. In the illustrated embodiment, any fluid directed towards the drain flows through the mixing cassette 500. Referring again to Figure 46B, the fluid drain port 8006 is located on the fluid side of the cassette 500.

[0272] Once the dialysate is mixed, it flows to the sensor cassette (1504 in Figure 51B). After it is determined that the dialysate is not within the set parameter / threshold, the dialysate is sent back into the mixing cassette 500, through the flat conduit 1400 to the external dialysate cassette 600, then back to the conduit check valve conduit 1200, and then through the mixing cassette 500 to the drain fluid outlet.

[0273] Referring here to Figures 46D and 46E, various pods 502, 504, 506, 602, 604, 702, 704, 706, and 708 are shown. Each pod housing is similarly configured, but the inside of the pod housing differs depending on whether the pod is a pod pump 502, 504, 602, 604, 702, or a balancing chamber pod 706, 708, or a mixing chamber pod 504.

[0274] Referring here to Figures 46D and 46E, along with Figures 51A and 51B, various pods are shown in both the fluid flow path and the cassette system. Pod 502 is a water pod pump, and 504 is a bicarbonate pod pump for the mixing cassette 500 (supplying water to the bicarbonate). Pod 506 is a mixing chamber. The dialysate is mixed in the mixing chamber 506 and then flows from the mixing cassette 500 to the sensor cassette 1504. If the dialysate is deemed acceptable, it flows through the mixing cassette dialysate tank outlet to the dialysate tank 1502. However, if the dialysate is deemed unacceptable, the fluid is sent back into the cassette 500, then through the 1400 conduit to the external dialysate cassette 600, then through the 1200 check valve conduit and out through the mixing cassette 500 to the drain outlet.

[0275] Referring to Figures 46A to 46C along with Figures 51A to 51B, an external dialysate cassette is shown between the mixing cassette 500 and the internal dialysate cassette 700. Pod pumps 602 and 604 draw dialysate from the dialysate tank 1502 and send it to the equilibrium chambers 706 and 708 in the internal dialysate cassette 700 (driving force for the dialysate). The external dialysate cassette 600 pushes the dialysate into the internal dialysate cassette (i.e., the pumps in the internal dialysate cassette 700 do not draw in the dialysate). Therefore, from the external dialysate cassette 600, the dialysate is sent from the dialysate tank 1502, through the heater 1506, through the ultrafiltration device 1508, and then into the internal dialysate cassette 700.

[0276] Here, with further reference to Figures 46D and 46E along with Figures 51A-51B, the internal dialysate cassette 700 includes a metering pod 8038 (i.e., an ultrafiltration metering pod), equilibrium pods 706, 708 and pod pumps 702, 704. The internal dialysate cassette 700 also includes fluid outlets and fluid inlets. These inlets and outlets include an outlet to the dialysis machine 1510, an inlet from the dialysis machine 1510 and a dialysate inlet (the ultrafiltration membrane 1508 connects to the ports of the internal dialysate cassette). The fluid inlets and outlets are also included for DCA and DCV connections during priming and disinfection. Various conduits (1200, 1300, 1400) serve as fluid communication between cassettes 500, 600, and 700 and are used to allow fluid to pass through to the mixing cassette 500 to flow out along with the dialysate fluid flow. The largest check valve 1300 (also shown in Figure 50B) is the largest check valve and is used during disinfection. This tube is relatively large to accommodate blood clots and other contaminants flowing through the conduit during disinfection in a preferred embodiment.

[0277] In exemplary embodiments, the valves and pumps of the cassette system are pneumatically driven. The pneumatic source is attached to the cassette via individual tubes. Thus, each pump, balance pod, or valve includes individual tube connections to a pneumatically operated manifold (not shown). Referring here to Figures 52A to 52F, the tubes are connected to at least one block 1600 in exemplary embodiments. In some embodiments, two or more blocks are used to connect various tubes. The block 1600 is placed in the manifold and then appropriately connected to the pneumatic actuator. This allows for easy connection of the pneumatic tubes to the manifold.

[0278] Referring again to Figure 46, in one embodiment, the cassette system includes a spring 8034 that functions to hold the system together. The spring 8034 is attached to the mixing cassette 500 and the internal dialysate cassette 700 via a fastener 8036. However, in other embodiments, but not limited to, any other means and devices that help maintain the system in the correct orientation may be used, such as latching means or elastic means.

[0279] Referring here to Figures 47A–47C, exemplary embodiments of the pod are shown. The pod includes two fluid ports 902, 904 (inlet and outlet), and in various embodiments, the pod may be configured in a different manner. Various embodiments of the structure are described in U.S. Patent Application No. 11 / 787,212, filed on 13 April 2007, entitled "Fluid Pumping Systems, Devices and Methods," which is incorporated herein by reference as a whole.

[0280] Referring here to Figures 47A, 47D, and 47E, the groove 906 of the chamber is shown. The groove 906 is included in each half of the pod housing. In other embodiments, the groove is not included, and in some embodiments, the groove is included in only one half of the pod.

[0281] Referring here to Figures 48A and 48B, exemplary embodiments of membranes used in pod pumps 502, 504, 602, 604, 702, and 704 are shown. These membranes are shown and described in relation to Figure 5A. In other embodiments, any of the membranes shown in Figures 5B to 5D can be used. Figure 49 shows an exploded view of an assembled pod pump according to an exemplary embodiment.

[0282] Various aspects of the present invention include one or more "pod pumps" used for various purposes. A schematic structure of a pod pump is described here, but as mentioned above, this structure can be modified for various applications, such as a pump, balancing chamber, mixing chamber, etc. Furthermore, the pod pump can be placed anywhere in the system, for example, on top of a cassette, between two or more cassettes, etc.

[0283] Generally, a pod pump includes a rigid chamber (which may have any preferred shape, e.g., spherical, elliptical, etc.), and the pod pump may include a flexible partition dividing each chamber into a first and second half. In some cases, the rigid chamber is a spheroid. As used herein, “spheroid” generally corresponds to an ellipse rotated about one of the principal, major, or minor axes, and means any three-dimensional shape, including three-dimensional oval, flattened and oblong spheroids, spheres, and substantially equivalent shapes.

[0284] Each half of a pod pump may have at least one inlet valve and often (but not always) at least one outlet valve (in some cases, the same port can be used for both the inlet and outlet). The valves may be, for example, on-off valves or bidirectional proportional valves. For example, the valve on one side of the chamber may be a bidirectional proportional valve, one end connected to a high-pressure source and the other to a low-pressure (or vacuum) sink, and the valve on the other half may be opened and closed to direct the fluid flow.

[0285] In some embodiments, the partition wall has varying cross-sectional thicknesses. Thinner, thicker, or variable-thickness partition walls can be used to correspond to the strength, bending properties, and other characteristics of the selected partition wall material. It is also possible to control the partition wall using thinner, thicker, or variable thickness wall thicknesses, thereby promoting easier bending in some areas than in others, thereby assisting in pumping action and controlling the flow of the target fluid within the pump chamber. In this embodiment, the partition wall is shown to have its thickest cross-sectional region closest to its center. However, in other embodiments having partition walls with variable cross-sections, the thickest and thinnest regions can be anywhere on the partition wall. Thus, for example, a relatively thin cross-section may be located near the center, and a relatively thick cross-section may be located near the periphery of the partition wall. In one embodiment of the partition wall, the partition wall has a tangential slope in at least one portion, while in other embodiments, the partition wall is perfectly smooth or substantially smooth.

[0286] The partition can be fabricated from any flexible material having the desired durability and compatibility with the target fluid. The partition can be fabricated from any material that can bend in response to the pressure or vacuum of the fluid, liquid, or gas applied to the working chamber. The partition material can also be selected for specific biocompatibility, temperature compatibility, or compatibility with various target fluids that may be extruded by or introduced into the chamber to facilitate the movement of the partition. In exemplary embodiments, the partition is fabricated from high-stretch silicone. However, in other embodiments, the partition is fabricated from any elastomer or rubber, including, but not limited to, silicone, urethane, nitrile, EPDM, or any other rubber, elastomer, or flexible material.

[0287] The shape of the partition wall is determined by several variables, including, but not limited to, the shape of the chamber, the size of the chamber, the characteristics of the fluid being supplied, the volume of fluid being supplied per stroke, and the means or mode of mounting the partition wall to the housing. The size of the partition wall is determined by several variables, including, but not limited to, the shape of the chamber, the size of the chamber, the characteristics of the fluid being supplied, the volume of fluid being supplied per stroke, and the means or mode of mounting the partition wall to the housing. Therefore, depending on these and other variables, the shape and size of the partition wall may differ in various embodiments.

[0288] The partition can have any thickness. However, in some embodiments, the thickness ranges from about 0.0508 mm (0.002 inches) to about 3.175 mm (0.125 inches) (1 inch = 2.54 cm). Depending on the material used for the partition, the desired thickness may vary. In one embodiment, high-stretch silicone with thicknesses ranging from about 0.381 mm (0.015 inches) to about 1.27 mm (0.050 inches) is used. However, in other embodiments, the thickness may differ.

[0289] In exemplary embodiments, the partition wall is pre-formed to include a substantially dome shape in at least a portion of the partition wall's area. In this case as well, the dimensions of the dome may vary based on some or more of the variables described above. However, in other embodiments, the partition wall may not include a pre-formed dome shape.

[0290] In exemplary embodiments, the partition dome is formed using liquid injection molding. However, in other embodiments, the dome can be formed using compression molding. In alternative embodiments, the partition is substantially flat. In other embodiments, the size, width, or height of the dome may vary.

[0291] In various embodiments, the bulkhead can be held in place by various means and methods. In one embodiment, the bulkhead is clamped between several parts of the cassette, and in some of these embodiments, the rim of the cassette may include features for gripping the bulkhead. In other embodiments, the bulkhead is clamped to the cassette using at least one bolt or other device. In another embodiment, the bulkhead is overmolded with a piece of plastic, and the plastic is then welded or otherwise attached to the cassette. In another embodiment, the bulkhead is clamped between an intermediate plate and a bottom plate. Although several embodiments of attaching the bulkhead to the cassette are described, any method or means of attaching the bulkhead to the cassette may be used. In one alternative embodiment, the bulkhead is attached directly to a part of the cassette. In some embodiments, the bulkhead is thicker at the edges than in other areas, where the bulkhead is clamped by a plate. In some embodiments, this relatively thicker area is a gasket, in some embodiments an O-ring, a ring or any other gasket of any shape.

[0292] In some embodiments of the gasket, the gasket is continuous with the partition wall. However, in other embodiments, the gasket is a separate component of the partition wall. In some embodiments, the gasket is made from the same material as the partition wall. However, in other embodiments, the gasket is made from a different material than the partition wall. In some embodiments, the gasket is formed by overmolding a ring around the partition wall. The gasket may be a ring or seal of any shape desired to complement the pod pump housing embodiment. In some embodiments, the gasket is a compression gasket.

[0293] Because it is a rigid chamber, a pod pump generally has a constant volume. However, within the pod pump, the first and second compartments can have different volumes depending on the position of the flexible partition that divides the chamber. Therefore, by forcing air into one compartment, the fluid in the other compartment of the chamber is discharged. However, the fluids typically cannot come into direct contact with each other within the pod pump because of the presence of the flexible partition.

[0294] Therefore, in one embodiment, the pod pump used for dispensing is configured to receive a control fluid in a first compartment and a fluid to be dispensed in a second compartment. The control fluid can be any fluid, and may be a liquid or a gas. In one embodiment, the control fluid is air. By drawing the control fluid away from the pod pump (for example, by vacuum or a pressure lower than the pressure inside the pod pump), the pod pump draws the fluid (e.g., blood, dialysate, etc.) into the other compartment of the pod pump. Similarly, by forcibly supplying the control fluid to the pod pump (for example, from a high-pressure source), the pod pump discharges the fluid. Alternatively, by controlling the valve in the second compartment, the fluid can be introduced through the first valve and then discharged through the second valve by the action of the control fluid.

[0295] As another example, a pod pump can be used for fluid equilibrium of dialysate, for example, as described above. In this case, instead of a control fluid, the fluid can be directed to each compartment of the pod pump. As mentioned above, the volume of the pod pump remains generally constant due to the rigid chamber. Therefore, when a first volume of fluid is drawn into the first compartment of the equilibrium pod, an equal volume of fluid is discharged from the second compartment of the equilibrium pod (assuming the fluid is generally incompressible under the operating conditions of the pod). Thus, by using such an equilibrium pad, equal volumes of fluid can be moved. For example, in Figure 5, the equilibrium pod allows fresh dialysate to enter the first compartment and used dialysate to enter the second compartment, and the volumetric flows of fresh and used dialysate can be equilibrium with respect to each other.

[0296] In some cases, a pod pump that does not include a flexible partition dividing the chamber is used. In such cases, the pod pump can be used as a mixing chamber. For example, the mixing chamber 189 in Figure 7A may be such a pod pump.

[0297] Figure 9 shows a non-limiting example of a pod pump. This figure is a cross-sectional view of a pneumatic control valve that can be used in a cassette embodiment. As used herein, “pneumatic” means that a flexible partition or other member is moved using air or other gas. (It should be noted that air is used merely as an example, and in other embodiments, other control fluids such as nitrogen (N2), CO2, water, oil, etc., can be used). Three rigid components are used, namely a “top” plate 91, an intermediate plate 92, and a “bottom” plate. (The terms “top” and “bottom” simply refer to the orientation shown in Figure 9. The valve can be oriented in any direction in actual use.) The top plate 91 and bottom plate 93 may be flat on both sides, while the intermediate plate 92 is provided with channels, indentations, and holes defining various fluid passages, chambers, and ports. The partition 90, together with the intermediate plate 92, defines the valve chamber 97. Air pressure is supplied through the air pressure port 96, thereby either by positive gas pressure pressing the partition wall 90 against the valve seat 99 to close the valve, or by negative gas pressure pulling the partition wall away from the valve seat to open the valve. The partition wall 90, the top plate 91, and the intermediate plate 92 define the control gas chamber 98. An indentation is formed in the intermediate plate 92, within which the partition wall 90 is positioned to form the control gas chamber 98 on one side of the partition wall and the valve chamber 97 on the other side.

[0298] The pneumatic port 96 is defined by a channel formed on the "top" surface of the intermediate plate 92, together with the top plate 91. By providing fluid communication between several valve chambers in the cassette, the valves can interlock with each other, thereby allowing all interlocked valves to be opened and closed simultaneously by a single pneumatic source. A channel formed on the "bottom" surface of the intermediate plate 92, together with the bottom plate, defines the valve inlet 94 and valve outlet 95. The hole formed through the intermediate plate 92 provides communication between the valve inlet 94 and the valve chamber 97 and between the valve chamber and the outlet 95 (through the valve seat 99).

[0299] The partition wall 90 is provided with a thickened rim 88, which fits tightly into a groove 89 in the intermediate plate 92. Thus, the partition wall 90 can be positioned in the groove 88 and held in place by the groove 88 before the top plate 91 is ultrasonically welded to the intermediate plate 92, and therefore the partition wall does not interfere with the ultrasonic welding of the two plates together, and thus the partition wall is not dependent on the ultrasonic welding to be precisely aligned so that the two plates are held in place. Thus, this valve can be easily manufactured without relying on the ultrasonic welding being performed to very tight tolerances. As shown in Figure 9, the top plate 91 may include additional material extending into the control gas chamber 98 to prevent the partition wall 90 from being excessively biased away from the groove 89 so that the thickened rim 88 of the partition wall does not protrude from the groove 89.

[0300] A pressure sensor can be used to monitor the pressure inside the pod. For example, by changing the air pressure applied to the pneumatic side of the chamber, the partition wall periodically reciprocates across the total chamber volume. In each cycle, when a vacuum is drawn into the pod by the air pressure, fluid is drawn out through the upstream valve of the inlet fluid port. Then, when a positive pressure is supplied to the pod by the air pressure, the fluid is subsequently discharged through the outlet port and downstream valve.

[0301] Figure 10 is a cross-sectional view of one embodiment of a pod pump that can be incorporated into an embodiment of a fluid control cassette. In some embodiments, the cassette incorporates several pod pumps and several valves fabricated according to the construction techniques shown in Figures 9 and 10. In such embodiments, the pod pump in Figure 10 is fabricated from different parts of the same three rigid components used to fabricate the valve in Figure 9. These rigid components are the “top” plate 91, the middle plate 92, and the “bottom” plate. (As mentioned above, the terms “top” and “bottom” simply refer to the orientation shown in Figure 9). To form the pod pump, the top plate 91 and the bottom plate 93 may include a generally hemispherical portion that together defines a hemispherical pod pump.

[0302] The partition wall 109 separates the central cavity of the pod pump into a chamber that receives the pumped fluid (pumping chamber) and another chamber that receives the control gas that operates the pump pneumatically (operating chamber). The inlet 94 allows the fluid to enter the pumping chamber, and the outlet allows the fluid to exit the pumping chamber. The inlet 94 and outlet 95 can be formed between the intermediate plate 92 and the bottom plate 93. Air pressure is supplied through the pneumatic port 106, and positive gas pressure presses the partition wall 109 against one wall of the pod pump cavity, minimizing the volume of the pumping chamber (as shown in Figure 10), or negative gas pressure pulls the partition wall towards the other wall of the pod pump cavity, maximizing the volume of the pumping chamber.

[0303] In some embodiments of pod pumps, various structures are used that include grooves in one or more plates exposed to the cavity of the pod pump. Among other advantages, forming grooves can prevent partitions from blocking inlet or outlet passages (or both) to fluid or air (or both).

[0304] A thickened rim 88 can be provided on the partition wall 109, which is tightly held in the groove 89 of the intermediate plate 92. Thus, as in the case of the valve chamber in Figure 9, the partition wall 109 can be positioned in and held by the groove 89 before the top plate 91 is ultrasonically welded to the intermediate plate 92, so that the partition wall does not interfere with the ultrasonic welding of the two plates together, and the partition wall is not dependent on the ultrasonic welding to be precisely aligned so that the two plates are held in place. Thus, this pod pump can be easily manufactured without relying on the ultrasonic welding being performed to very tight tolerances.

[0305] Figure 11A is a schematic diagram showing an embodiment of the pressure-actuated system 110 for a pod pump, such as that shown in Figure 10. In this example, air is used as the control fluid (for example, the pump is pneumatically driven). As described above, in other embodiments, other fluids (for example, water) can also be used as the control fluid.

[0306] In Figure 11A, the pressure-operated system 110 alternately provides positive and negative pressure to the gas in the operating chamber 112 of the pod pump 101. The pneumatically operated system 110 includes an electronic controller 119, along with an operating chamber pressure transducer 114, a variable positive supply valve 117, a variable negative supply valve 118, a positive pressure gas reservoir 121, a negative pressure gas reservoir 122, a static pressure reservoir pressure transducer 115, and a negative pressure reservoir pressure transducer 116.

[0307] The positive pressure reservoir 121 provides positive pressure of control gas to the working chamber 112, biasing the partition wall 109 toward the position where the pumping chamber 111 has its minimum volume (i.e., the position where the partition wall is in contact with the rigid pumping chamber wall). The negative pressure reservoir 122 provides negative pressure of control gas to the working chamber 112, biasing the partition wall 109 in the opposite direction toward the position where the pumping chamber has its maximum volume (i.e., the position where the partition wall is in contact with the rigid working chamber wall).

[0308] In this example, a valve mechanism is used to control the fluid communication between each of these reservoirs 121 and 122 and the working chamber 112. In Figure 11A, separate valves are used for each reservoir; namely, the positive supply valve 117 controls the fluid communication between the positive pressure reservoir 121 and the working chamber 112, and the negative supply valve 118 controls the fluid communication between the negative pressure reservoir 122 and the working chamber 112. These two valves are controlled by an electronic controller 119. (Alternatively, a single three-way valve can be used instead of the two separate valves 117 and 118.) In some cases, the positive supply valve 117 and the negative supply valve 118 are variable throttle valves, as opposed to binary on-off valves. The advantages of using variable valves will be discussed later.

[0309] The controller 119 also receives pressure information from three pressure transducers shown in Figure 11A: the working chamber pressure transducer 114, the positive pressure reservoir pressure transducer 115, and the negative pressure reservoir pressure transducer 116. As their names suggest, these transducers measure the pressure in the working chamber 112, the positive pressure reservoir 121, and the negative pressure reservoir 122, respectively. The controller 119 monitors the pressure in the two reservoirs 121 and 122 to ensure they are properly pressurized (positively or negatively). One or more compressor-type pumps can be used to obtain the desired pressure in these reservoirs 121 and 122.

[0310] In one embodiment, the pressure provided by the positive pressure reservoir 121 is strong enough to press the partition wall 109 against the rigid pumping chamber wall under normal conditions. Similarly, the negative pressure (i.e., vacuum) provided by the negative pressure reservoir 122 is preferably strong enough to press the partition wall against the rigid working chamber wall under normal conditions. However, in some embodiments, these positive and negative pressures provided by reservoirs 121 and 122 are within a sufficiently safe range so that the positive or negative pressure applied to the partition wall 109 is not strong enough to harm the patient, even if either the positive or negative supply valve 118 is fully open.

[0311] In one embodiment, the controller 119 monitors pressure information from the working chamber pressure transducer 114 and, based on this information, controls the valve mechanism (valves 117, 118) to move the partition wall 109 to its minimum pumping chamber volume position, and after reaching this position, pulls the partition wall 109 back to its maximum pumping chamber volume position.

[0312] The pressure-actuated system (including the working chamber pressure transducer 114, the positive pressure reservoir pressure transducer 115, the negative pressure reservoir pressure transducer 116, the variable positive supply valve 117, the variable negative supply valve 118, the controller 119, the positive pressure gas reservoir 121, and the negative pressure gas reservoir 122) is located entirely or largely outside the insulated space (element 61 in Figure 6). Components that come into contact with blood or dialysate (i.e., the pod pump 101, the inlet valve 105, and the outlet valve 107) may, in some cases, be placed within the insulated space to allow them to be disinfected more easily.

[0313] Figure 11B shows another example of a pressure actuation system 110 for a pod pump. In this example, the pod pump 101 includes a pumping chamber 111, an actuation chamber 112, and a partition wall 109 separating the two sides. Fluid ports 102 and 104 allow access for fluid entering and leaving the pumping chamber 111, for example, by using a fluid valve (not shown). However, within the pod pump 101, the fluid ports 102 and 104 include a “volcano” port 126 having a generally raised shape, so that when the partition wall 109 contacts the port, the partition wall can form a tight seal against the port. Figure 11B also shows a three-way valve connecting pressure reservoirs 121, 122. The three-way valve 123 is in fluid communication with the actuation chamber 112 by a single port in this example.

[0314] It will be understood that, instead of the two-reservoir pneumatically operated system shown in Figures 11A and 11B, other types of operating systems can be used to move the bulkhead back and forth.

[0315] As described above, the positive supply valve 117 and negative supply valve 118 of the pneumatically operated system 110 in Figure 11A are preferably variable throttle valves, as opposed to binary on-off valves. By using variable valves, the pressure applied to the working chamber 112 and the bulkhead 109 can be easily controlled to be only a portion of the pressure in the reservoirs 121, 122, instead of applying the full reservoir pressure to the bulkhead. Thus, although the pressure required to operate the pod pumps may differ for each pod pump, the same reservoir or set of reservoirs can be used for different pod pumps. Naturally, the reservoir pressure must be greater than the desired pressure applied to the bulkheads of the various pod pumps, but one pump can be operated at, for example, half the reservoir pressure, and another pod pump can be operated in the same reservoir, but at, for example, one-quarter of the reservoir pressure. Therefore, even though different pod pumps in a dialysis system are designed to operate at different pressures, all of these pod pumps share the same reservoir or set of reservoirs, but can still be driven at different pressures by using variable valves. The pressure used in a pod pump can be modified to accommodate conditions that may increase or change during a dialysis procedure. For example, if the flow through the system's tubing is obstructed by tubing twisting, one or both of the positive or negative pressures used in the pod pump can be increased to overcompensate for the increased restriction.

[0316] Figure 12 is a graph showing how the pressure applied to the pod pump can be controlled using a variable valve. The vertical axis represents the pressure using PR+ and PR-, which represent the pressures in the positive and negative reservoirs (elements 121 and 122 in Figure 11A), respectively, and PC+ and PC-, which represent the positive and negative control pressures acting on the pod pump partition, respectively. As shown in Figure 12, a positive pressure is applied to the working chamber (to push fluid out of the pumping chamber) from time T0 to approximately time T1. By repeatedly increasing and decreasing the flow restriction provided by the positive variable valve (element 117 in Figure 11A), the pressure applied to the working chamber can be maintained at approximately the desired positive control pressure PC+. The pressure changes in a limiting curve around the desired control pressure. A working chamber pressure transducer (element 114 in Figure 11A), which is in communication with the working chamber, measures the pressure inside the working chamber and transmits the pressure measurement information to a controller (element 119 in Figure 11A). The controller controls a variable valve so that the pressure in the working chamber changes to around the desired control pressure PC+. In the absence of fault conditions, the bulkhead is pressed against the rigid wall of the pumping chamber, thereby ending the stroke. The controller determines that the end of the stroke has been reached when the pressure measured in the working chamber does not decrease further even as the throttling provided by the variable valve is reduced. In Figure 12, the end of the discharge stroke occurs around time T1. Once the end of the stroke is detected, the controller completely closes the variable valve, thereby preventing the pressure in the working chamber from rising far above the desired control pressure PC+.

[0317] After the positive variable valve closes, the negative variable valve (element 118 in Figure 11A) is partially opened, allowing the negative pressure reservoir to draw gas from the working chamber and thus draw fluid into the pumping chamber. (As shown in Figure 12, negative pressure is applied to the working chamber from immediately after T1 until approximately time T2). Similar to the discharge (positive pressure) stroke, the aforementioned stroke, which repeatedly increases and decreases the flow restriction provided by the negative variable valve, can maintain the pressure applied to the working chamber at approximately a desired negative control pressure PC- (weaker than the pressure in the negative pressure reservoir). The pressure changes sinusoidally around the desired control pressure. The working chamber pressure transducer passes pressure measurement information to the controller, which controls the variable valve so that the pressure in the working chamber changes around the desired control pressure PC-. In the absence of fault conditions, the bulkhead is pulled against the rigid wall of the working chamber, thereby ending the discharge (negative pressure) stroke. As described above, the controller determines that the stroke has ended when the partial vacuum measured in the working chamber does not decrease further, even as the throttling provided by the variable valve is reduced. In Figure 12, the end of the draw stroke occurs at approximately time T2. Once the end of the stroke is detected, the controller completely closes the variable valve, thereby preventing the vacuum in the working chamber from rising far above the desired negative control pressure PC-. Once the draw stroke is ended, the positive variable valve can be partially opened to initiate a new discharge stroke under positive pressure.

[0318] Therefore, each pod pump in this example uses two variable orifice valves to restrict the flow from a positive pressure source to a negative pressure source. The pressure in the working chamber is monitored, and the controller uses this pressure measurement to determine the appropriate commands for both valves to achieve the desired pressure in the working chamber. Some advantages of this configuration are that the filling and discharge pressures can be precisely controlled to reach the desired flow rate while taking pressure limits into consideration, and that the pressure can be varied using small sinusoidal signature commands. This signature can be monitored to determine when the pump has reached the end of its stroke.

[0319] Another advantage of using variable valves instead of binary valves is that valve wear and tear are reduced by only partially opening and closing the variable valve. Repeatedly "striking" a binary valve to fully open and close it can shorten the valve's lifespan.

[0320] If the end of a stroke is detected and the integral of the correlation function is very small, this may indicate that an obstruction occurred in the stroke and it did not complete properly. It may be possible to distinguish upstream obstructions from downstream obstructions by determining whether the obstruction occurred in the filling stroke or the discharge stroke (this may be difficult in the case of obstructions occurring near the end of a stroke when the partition is close to the chamber wall). Figures 13A and 13B show the detection of an obstruction (when an obstruction is detected, the chamber pressure drops to 0).

[0321] Under normal operation, the integral of the correlation function increases as the stroke progresses. If this value remains small or does not increase, the stroke is either very short (in the case of very low impedance flow or blockage) or the actual pressure cannot track the desired sinusoidal pressure due to a faulty valve or pressure signal. The absence of correlation can be detected and used for error handling in these cases.

[0322] Under normal operating conditions, the flow controller's control loop adjusts the pressure in response to any changes in flow rate. If the circuit's impedance increases dramatically and the pressure limit saturates before the flow can reach the target flow rate, the flow controller will be unable to adjust the pressure higher to reach the desired flow rate. These situations can occur if the line is partially blocked, such as when a blood clot forms in the circuit. Pressure saturation before the flow rate reaches the target can be detected and used for error handling.

[0323] If there are problems with the valve or pneumatics, such as fluid valve leaks or noisy pressure signals, the ripple may persist unclearly throughout the stroke, and the stroke termination algorithm may not detect a sufficient change in the pressure ripple to detect the end of the stroke. For this reason, a safety check is added to detect whether the time to complete the stroke is excessive. This information can be used for error handling.

[0324] In a dual pump such as pump 13 in Figure 3A, the two pump chambers can be operated periodically in opposite directions to produce a pump cycle. A phase relationship can be selected from 0° (both chambers act in the same direction) to 180° (chambers act in opposite directions). Since it may be impossible to move both chambers in the same direction simultaneously, the phase movement may be modified somewhat in some cases, thereby potentially opening both the inlet and outlet valves, and the end of the stroke may not be properly detected.

[0325] By selecting a 180° phase relationship, a continuous flow is produced in and out of the pod. This is the nominal pump mode when continuous flow is desired. Setting a 0° phase relationship is useful for single-needle flow. The pod is first filled from the needle and then discharged to the same needle. Using operation with phases between 0° and 180°, a push / pull relationship (hemodiafiltration / continuous backflush) can be achieved across the dialysis machine. Figures 8A to 8C are graphs of these phase relationships.

[0326] A pod pump can control the flow rate of fluid through various subsystems. For example, a sinusoidal pressure waveform can ...

Claims

[Claim 1] The system described in the statement.

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