Blood processing system and method

Abstract

To provide a dialysis system equipped with a plurality of actuators cooperating to execute a dialysis function and a plurality of sensors cooperating to monitor the dialysis function.SOLUTION: A dialysis system includes a user interface model layer, a treatment layer lower in order than the user interface model layer, and a machine layer lower in order than the treatment layer. The user interface model layer manages a state of a graphical user interface and receives input. The treatment layer executes a state machine for generating a treatment command on the basis of the input from the graphical user interface. The machine layer provides a command to actuators on the basis of the treatment command.SELECTED DRAWING: Figure 2A

Description

[Technical Field]

[0001] The present invention relates to hemodialysis and similar dialysis systems, i.e., systems for treating blood and other bodily fluids outside the body. In embodiments, the systems include various systems and methods that can make hemodialysis more efficient, easier, and / or less expensive. Related Applications This application claims the benefit under 35 U.S.C. §119(e) of U.S. Provisional Patent Application No. 61 / 489,544, filed May 24, 2011, entitled "Blood Treatment Systems and Methods," and U.S. Provisional Patent Application No. 61 / 498,394, filed June 17, 2011, entitled "Blood Treatment Systems and Methods," both of which are incorporated herein by reference in their entireties. [Background technology]

[0002] FIG. 1 is a schematic diagram of a hemodialysis system. System 5 includes two flow paths: blood flow path 10 and dialysate flow path 20. Blood is pumped from a patient. A blood flow pump 13 causes the blood to flow around blood flow path 10, pumping the blood from the patient, passing it through dialyzer 14, and returning it to the patient. Optionally, the blood passes through other elements, such as a filter and / or air trap 19, before returning it to the patient. Additionally, in this example, an anticoagulant is supplied from anticoagulant supply 11 through anticoagulant valve 12.

[0003] A dialysate pump 15 pumps dialysate from a dialysate supply 16 and passes the dialysate through the dialyzer 14. The dialysate then passes through a relief valve 18 and / or returns to the dialysate supply through the dialysate pump 15. A dialysate valve 17 controls the flow of dialysate from the dialysate supply 16. The dialyzer is configured so that blood from the blood flow circuit flows through small tubes and dialysate circulates around the outside of the tubes. Therapy occurs when waste molecules (e.g., urea, creatinine, etc.) and water pass from the blood through the walls of the tubes and into the dialysate. At the end of treatment, the dialysate is drained. Summary of the Invention [Problem to be solved by the invention]

[0004] Many factors make hemodialysis inefficient, difficult, and costly. These factors include the complexity of hemodialysis, the safety issues associated with hemodialysis, and the large volume of dialysate required for hemodialysis. Furthermore, hemodialysis typically requires skilled personnel and is performed in a dialysis center. Therefore, improving the ease and efficiency of the dialysis process impacts the cost of the procedure and patient outcomes. [Means for solving the problem]

[0005] The present invention relates to hemodialysis systems and similar dialysis systems. In embodiments, the subject matter of the present invention includes related products, alternative solutions to a given problem, and / or multiple different uses of one or more of the systems or products. Although the various systems and methods disclosed herein are described in the context of hemodialysis, the various systems and methods disclosed herein may be suitable for other dialysis systems and / or any extracorporeal system capable of treating blood or other bodily fluids, such as hemofiltration, hemodiafiltration, etc.

[0006] In one embodiment, the system includes four flow paths: blood, inbound dialysate, outbound dialysate, and a dialysate mixture flow path. In some embodiments, the four flow paths are combined in a single cassette. In other embodiments, the four flow paths are each located in a corresponding cassette. In yet other embodiments, two or more flow paths are included in a single cassette.

[0007] In one embodiment, a hemodialysis system is provided having at least two flow paths, the two flow paths being integrally formed in 1) a blood flow pump cassette, 2) an internal dialysate cassette, 3) an external dialysate cassette, and 4) a mixing cassette. The cassettes are in communication with each other. In some embodiments, one or more aspects of these cassettes are combined into a single cassette.

[0008] In yet another embodiment, a hemodialysis system is provided that includes a blood flow path through which untreated blood is drawn from a patient, passes through a dialyzer, and returns treated blood to the patient. The blood flow path includes at least one blood flow pump mounted on a removable cassette. The hemodialysis system can further include a first receiving structure for receiving the cassette of the blood flow path, a dialysate flow path through which dialysate flows from a dialysate supply through the dialyzer, a second receiving structure for receiving the dialysate flow path, and a control fluid path that delivers control fluid from a drive mechanism to the cassette to drive each of the blood flow pumps and the dialysate pump. In some embodiments, the dialysate flow path includes at least one dialysate pump mounted on a removable cassette.

[0009] In yet another embodiment, a hemodialysis system is disclosed. In this embodiment, the hemodialysis system includes a blood flow path through which untreated blood is pumped from a patient, passes through a dialyzer, and treat- ed blood is returned to the patient. The blood flow path includes at least one blood valve. The hemodialysis system further includes the blood valve, a dialysate mixing system (including at least one dialyzer valve) in communication with the dialyzer, and a control fluid path that carries a control fluid from a drive mechanism to the blood valve to drive a heating means or heater for heating the dialysate.

[0010] In yet another embodiment, a hemodialysis system is disclosed that includes a blood flow path through which untreated blood is pumped from a patient and passed through a dialyzer, and treated blood is returned to the patient. The blood flow path includes at least one blood flow pump. The hemodialysis system further includes a dialysate flow path through which dialysate flows from a dialysate supply through the dialyzer. The dialysate flow path includes at least one pneumatic pump.

[0011] In one aspect, the present invention relates to a hemodialysis system, in one embodiment, comprising a blood flow path, a first cassette defining an internal dialysate flow path, a dialyzer in communication with the blood flow path and the internal dialysate flow path, a second cassette defining an external dialysate flow path, and a membrane connecting the first cassette to the second cassette.

[0012] In yet another embodiment, a hemodialysis system includes a blood flow path, an internal dialysate flow path, a dialyzer in communication with the blood flow path and the internal dialysate flow path, an external dialysate flow path, a membrane communicating between the internal dialysate flow path and the external dialysate flow path, a first dialysate pump that pumps dialysate from the internal dialysate flow path, and a second dialysate pump that pumps dialysate from the external dialysate flow path, the second dialysate pump and the first dialysate pump being operably connected such that the flow in the internal dialysate flow path is substantially equal to the flow in the external dialysate flow path.

[0013] In yet another embodiment, the dialysate system includes a blood flow path through which blood is pumped from a patient and passed through the dialyzer, a dialysate flow path through which dialysate flows from a dialysate supply through the dialyzer, and in one embodiment, the dialysate flow path includes a balancing cassette that controls the amount of dialysate passing through the dialyzer, a mixing cassette that forms dialysate from water, and a directing cassette that routes water from a water supply to the mixing cassette and dialysate from the mixing circuit to the balancing circuit.

[0014] In yet another embodiment, the hemodialysis system includes a cassette system including a directing cassette, a mixing cassette, and a balancing cassette. In some embodiments, the directing cassette can distribute water from a water supply to the mixing cassette and distribute dialysate from the mixing cassette to the balancing cassette. The mixing circuit can mix water from the directing cassette with dialysate from a dialysate supply to form a precursor. The balancing cassette can control the amount of dialysate passing through the dialyzer.

[0015] In some embodiments, the hemodialysis system includes a blood flow path through which blood is pumped from a patient and passed through the dialyzer; a blood flow path including a blood flow pump; a dialysate flow path through which dialysate flows from a dialysate supply through the dialyzer; the dialysate flow path including a dialysate pump; and a control fluid path through which a control fluid drives the blood flow pump and the dialysate pump.

[0016] In yet another embodiment, the hemodialysis system includes a blood flow path through which blood is pumped from a patient and passes through the dialyzer, and a dialysate flow path through which dialysate flows from a dialysate supply and through the dialyzer. In some embodiments, the dialysate flow path includes at least one pneumatic pump.

[0017] In yet another embodiment, the hemodialysis system includes a first pump having a pump chamber and a drive chamber, a second pump having a pump chamber and a drive chamber, a control fluid communicating with each drive chamber of the first pump and the second pump, and a controller capable of pressurizing the control fluid and controlling the drive of the first pump and the second pump.

[0018] In yet another embodiment, the hemodialysis system includes a first valve having a valve chamber and an actuation chamber, a second valve having a valve chamber and an actuation chamber, a control fluid communicating with each actuation chamber of the first valve and the second valve, and a controller capable of pressurizing the control fluid to control actuation of the first valve and the second valve.

[0019] In one embodiment, the hemodialysis system includes a blood flow path through which blood is pumped from a patient and passed through a dialyzer, a cassette including at least a portion of the blood flow path, and a spike integrally formed with the cassette, the spike capable of receiving a vial of fluid, the integrally formed spike communicating with the blood flow path within the cassette.

[0020] In another embodiment, the hemodialysis system includes a blood flow path through which blood is pumped from a patient and passed through the dialyzer, a dialysate flow path through which dialysate flows from a dialysate supply and through the dialyzer, and a gas supply in communication with the dialysate flow path such that, when activated, gas from the gas supply drives the dialysate through the dialyzer and returns blood in the blood flow path to the patient. The dialyzer drives the dialysate from the dialysate flow path to the blood flow path.

[0021] In yet another embodiment, a hemodialysis system includes a blood flow path through which untreated blood is pumped from a patient and passed through a dialyzer, a dialysate flow path through which dialysate flows from a dialysate supply to the dialyzer, a fluid supply, a chamber in communication with the fluid supply and the dialysate flow path, and a pressurizer that pressurizes the fluid supply to pressurize a septum against the dialysate in the chamber, thereby forcing the dialysate through the dialyzer and returning blood in the blood flow path to the patient. The dialyzer causes the dialysate to flow from the dialysate flow path to the blood flow path. The chamber has a septum that separates fluid from the fluid supply from the dialysate in the dialysate flow path.

[0022] In yet another embodiment, the hemodialysis system includes a blood flow path through which untreated blood is pumped to a patient and passes through a dialyzer, a dialysate flow path through which dialysate flows from a dialysate supply through the dialyzer, and a pressurizing device that pressurizes the dialysate in the dialysate flow path to force it into the blood flow path. The dialysate flow path and the blood flow path are in communication with each other.

[0023] In one embodiment, the hemodialysis system includes a first housing containing a positive displacement pump driven by a control fluid, a fluid path connecting the positive displacement pump with a control fluid pump, and a second housing containing the control fluid pump, the second housing being detachable from the first housing.

[0024] In another embodiment, the hemodialysis system includes a housing having 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 electrical components that do not heat to a temperature of 60°C or greater when the first compartment is heated to a temperature of at least about 80°C.

[0025] In yet another embodiment, the hemodialysis system includes a blood flow path including at least one blood valve through which untreated blood is pumped from a patient and passed through a dialyzer; a control fluid path that carries a control fluid from a drive mechanism to the blood valve to drive the blood valve; a dialysate mixing system in communication with the dialyzer and including at least one dialysate system valve; and a heater that heats the dialysate.

[0026] Another aspect of the present invention relates to a valve system. In an embodiment, the valve system includes a valve housing containing a plurality of valves. At least two of the valves each comprise a valve chamber and an actuation chamber. Each of the at least two valves is actuated by a control fluid in the actuation chamber. The valve system further includes a control housing having a plurality of fluid interface ports for communicating with the control fluid from a base unit, and a plurality of tubes extending between the valve housing and the control housing. Each tube communicates one of the fluid interface ports with at least one of the actuation chambers, thereby allowing the base unit to actuate the valve by pressurizing the control fluid in the fluid interface ports.

[0027] In an embodiment of the present invention, the valve includes a first plate, a second plate, a third plate, and a partition wall. The second plate has a recess on the side facing the first plate, the recess having a groove formed therein, the groove opening toward the first plate. The second plate is disposed between the first and third plates. The partition wall is disposed within the recess between the first and second plates. The partition wall has an edge, and the edge is held within the groove. The second plate includes a valve seat. The partition wall is pressed by air pressure to seal and close the valve seat. The groove surrounds the valve seat. In an embodiment, a valve inlet and a valve outlet are formed between the second and third plates. In an embodiment, a passage for generating air pressure is disposed between the first and second plates.

[0028] A further aspect of the present invention discloses a pump system. In one embodiment, the pump system includes a pump housing containing a plurality of pumps. At least two of the pumps each include a pump chamber and a drive chamber. Each of the at least two pumps is drivable by a control fluid in the drive chamber. The pump housing includes a control housing having a plurality of fluid interface ports for communicating with the control fluid from a base unit, and a plurality of tubes extending between the pump housing and the control housing. Each of the tubes communicates between one of the fluid interface ports and at least one of the drive chambers, thereby allowing the base unit to drive the pumps by pressurizing the control fluid in the fluid interface ports.

[0029] In another aspect of the present invention, a pump cassette is disclosed. In some embodiments, the pump cassette includes at least one fluid inlet, at least one fluid outlet, a fluid passage connecting the at least one fluid inlet and the at least one fluid outlet, and a spike for attaching a vial to the cassette. In some embodiments, the spike communicates with the fluid passage.

[0030] In one aspect of the present invention, a pump cassette for balancing fluid flow to and from a target site is disclosed. In one embodiment, the pump cassette includes a cassette inlet, a supply line to the target site, a return line from the target site, a cassette outlet, a pump mechanism for driving fluid from the cassette inlet to the supply line and from the return line to the cassette outlet, and a balance chamber. In one embodiment, the pump mechanism includes a pod pump having a rigid, curved wall defining a pump volume and having an inlet and an outlet, a diaphragm disposed within the pump volume, and an actuation port connecting the pod pump to a pneumatic actuation system and actuating the diaphragm to allow fluid into and out of the pump volume. The pump diaphragm separates the fluid from a gas communicating with the pneumatic actuation system. In one embodiment, the balance chamber includes a rigid, curved wall defining a balance volume and a balance diaphragm disposed within the balance volume. The balance diaphragm separates the balance volume into a supply side and a return side. The supply side and the return side each have an inlet and an outlet. In some embodiments, 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.

[0031] In another embodiment, the pump system includes a system inlet, a supply line to a target site, a return line from the target site, a system outlet, a pumping mechanism for moving fluid from the system inlet to the supply line and from the return line to the system outlet, and a balance chamber.

[0032] In one embodiment, the pump mechanism includes a pod pump having a rigid spheroidal wall defining a rigid pump volume and having an inlet and an outlet, a pump diaphragm disposed within the spheroidal wall to the spheroid, and a port connecting the pod pump to a pneumatic drive system for actuating the diaphragm to move fluid into and out of the pump volume. In one embodiment, the pump diaphragm separates the fluid from a gas in communication with the pneumatic drive system.

[0033] In some embodiments, the balance chamber comprises a rigid spheroidal wall defining a balance volume, and a balance partition disposed within the spheroidal wall and extending to the spheroid. In some embodiments, the balance partition separates the balance volume into a supply side and a return side, each having an inlet and an outlet. In some embodiments, 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. Fluid from the return side outlet flows to the system outlet. The pump mechanism further comprises a valve mechanism disposed at each of the supply side and return side inlets and outlets. The valve mechanism is pneumatically actuated.

[0034] In a further aspect of the present invention, a cassette is disclosed. In one embodiment, the cassette comprises 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 pump capable of pumping a fluid through at least a portion of the second flow path, and at least two balance chambers. Each balance chamber comprises a rigid container, the rigid container including a partition wall separating the rigid container into a first compartment and a second compartment. The first compartment of each balance chamber is in communication with the first flow path, and the second compartment is in communication with the second flow path.

[0035] In another embodiment, the cassette includes a first fluid path connecting the first inlet to the first outlet, a second fluid path connecting the second inlet to the second outlet, a control fluid path, at least two pumps, and a balance chamber capable of maintaining a balance of flow between the first and second fluid paths. Each pump comprises a rigid container including a partition separating the rigid container into a first compartment and a second compartment. The first compartment of each pump is in communication with the control fluid path, and the second compartment is in communication with the second fluid path.

[0036] In yet another embodiment, the cassette comprises a rigid container including a first fluid path connecting a first inlet to a first outlet, a second fluid path connecting a second inlet to a second outlet, and a partition separating the rigid container into a first compartment and a second compartment, wherein, in operation, the first compartment is in communication with the first fluid path and the second compartment is in communication with the second fluid path.

[0037] In a further aspect of the present invention, a pump is disclosed. In one embodiment, the pump includes a first rigid element, a second rigid element, and a partition wall having a rim. The second rigid element has a groove formed therein on a side facing the first plate. The groove opens toward the first rigid element. The rim is retained within the groove by a friction fit, but the first rigid element does not contact the rim. In one embodiment, the first rigid element and the second rigid element at least partially define a pod pump chamber separated into individual chambers by the partition wall, and also at least partially define a flow path to the pod pump chamber. The groove surrounds the pod pump chamber.

[0038] In another embodiment, the pump includes a generally spherical container including a flexible diaphragm separating the rigid container into a first compartment and a second compartment, the first compartment and the second compartment not communicating with each other, and movement of the diaphragm by fluid entering the first compartment causes pumping of fluid within the second compartment.

[0039] In another embodiment, the pump is a reciprocating positive displacement pump. In one embodiment, the pump comprises a rigid chamber wall and a flexible diaphragm attached to the rigid chamber wall. The flexible diaphragm and the rigid chamber wall form a pump chamber. The pump further comprises an inlet port directing flow from the rigid chamber wall to the pump chamber, an outlet port directing flow from the pump chamber through the rigid chamber wall, and a restriction wall restricting movement of the rigid diaphragm and limiting the maximum volume of the pump chamber. The rigid restriction wall forms a drive chamber. The pump further comprises a pneumatic drive system intermittently applying a control pressure to the drive chamber. In one embodiment, the pneumatic drive system comprises a drive chamber pressure transducer for measuring pressure in the drive chamber, a gas tank having a first pressure, a variable valve mechanism for variably restricting gas flow between the drive chamber and the gas tank, and a controller receiving pressure information from the drive chamber pressure transducer and controlling the variable valve to thereby generate a control pressure within the drive chamber. The control pressure is less than or equal to the first pressure.

[0040] A further aspect of the invention discloses a method, in one embodiment, comprising providing a first pump comprising a pump chamber and a drive chamber and a second pump comprising a pump chamber and a drive chamber, delivering a common fluid to the drive chambers of each of the first pump and the second pump, and pressurizing the common fluid and passing the fluid through each of the first pump and the second pump.

[0041] In another embodiment, a 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, delivering a common fluid to each actuation chamber of the first valve and the second valve, and pressurizing the common fluid to at least partially pass the fluid through the first valve and the second valve.

[0042] In yet another embodiment, a method is provided for measuring the clearance rate of a dialyzer. The dialyzer is provided with a blood flow path. Untreated blood is pumped from a patient through the blood flow path and delivered to the dialyzer. Dialysate flows from a dialysate supply through the dialyzer in a dialysate flow path separated from the dialysate flow path by a membrane within the dialyzer. In one embodiment, the method includes passing a liquid through the dialysate flow path to the dialyzer to keep the membrane wet and prevent gas from flowing through the membrane; passing a gas through the blood flow path to the dialyzer to fill the blood flow path within the dialyzer with gas; measuring the volume of gas within the dialyzer; and calculating the clearance rate based on the volume of gas measured at the dialyzer.

[0043] In yet another embodiment, a method is a method for measuring the cleaning rate of a dialysis machine. In one embodiment, the method includes applying an air pressure differential across the dialysis machine, measuring a flow rate through the dialysis machine, and determining the cleaning rate of the dialysis machine based on the air pressure differential and the flow rate.

[0044] In yet another embodiment, the method is a method for measuring the cleaning rate of a dialysis machine. In one embodiment, the method includes passing water through the dialysis machine, measuring the amount of ions collected by the water after passing through the dialysis machine, and determining the cleaning rate of the dialysis machine based on the amount of ions collected by the water after passing through the dialysis machine. In another embodiment, the method includes passing water through the dialysis machine, measuring the conductivity of the water, and determining the cleaning rate of the dialysis machine based on the change in the conductivity of the water.

[0045] In one embodiment, the method is a method for introducing fluid into blood. In one embodiment, the method includes the steps of providing a cassette including an integrally formed spike for receiving a vial of fluid and a valve mechanism for controlling the flow of fluid from the vial into the cassette, attaching the vial containing the fluid to the spike, drawing blood through the cassette, and introducing the fluid from the vial into the blood.

[0046] In one embodiment, the method includes providing a hemodialysis system comprising a blood flow path through which untreated blood is pumped from a patient and passed through a dialyzer, and a dialysate flow path through which dialysate passes from a dialysate supply through the dialyzer; communicating the blood flow path and the dialysate flow path; and passing the dialysate through the dialysate flow path to deliver the blood in the blood flow path to the patient.

[0047] In another embodiment, a method includes providing a hemodialysis system comprising a blood flow path through which untreated blood is pumped from a patient and passed through the dialyzer, and a dialysate flow path through which dialysate is passed from a dialysate supply through the dialyzer; communicating the blood flow path and the dialysate flow path; and discharging a gas through the dialysate flow path to flow blood in the blood flow path.

[0048] In yet another embodiment, the method is a method of hemodialysis. In one embodiment, the method includes providing a blood flow path through which untreated blood is pumped from a patient and passed through the dialyzer; providing a dialysate flow path through which dialysate is passed from a dialysate supply through the dialyzer; providing a source material to prepare a total volume of dialysate; providing water to mix with the dialysate source material; and mixing a volume of water with a portion of the source material to prepare a first partial volume of dialysate. The first partial volume is small compared to the total volume. The method further includes pumping the partial volume of dialysate through the dialysate flow path and through the dialyzer; and pumping blood through the blood flow path and through the dialyzer. The first partial volume of dialysate is delivered to the dialyzer by the pump. The method further includes mixing a volume of water with a portion of the source material to prepare a second partial volume of dialysate and storing the second partial volume of dialysate in a container. The blood and a first partial volume of dialysate are pumped through the dialyzer.

[0049] In another example, a method includes passing blood and dialysate from a patient through a dialyzer included in a hemodialysis system at a first speed, and forming dialysate in the hemodialysis system at a second speed different from the first speed, and storing excess dialysate in a container included in the hemodialysis system.

[0050] Another aspect of the present invention relates to a hemodialysis system including a dialysis unit and a user interface unit. The dialysis unit includes an automation computer and a dialyzer. The user interface unit includes a user interface computer and a user interface, the user interface being configured to display information and receive input. The automation computer is configured to receive a request for safety-critical information from the user interface computer and access the safety-critical 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-critical information.

[0051] Another aspect of the invention relates to a method for managing a user interface in a hemodialysis system, the method including receiving input related to a dialysis process at a user interface associated with a user interface computer, and transmitting a request for safety-critical information from the user interface computer to an automation computer associated with a dialyzer in response to the input, the method further including accessing the safety-critical information on behalf of the user interface computer, and using the safety-critical information to display information related to the dialysis process via the user interface.

[0052] Yet another aspect of the present invention relates to a computer storage medium encoded with instructions that, when executed, perform a method including receiving input related 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-critical information from the user interface computer to an automation computer associated with the dialysis machine. The method further includes accessing the safety-critical information on behalf of the user interface computer, transmitting the safety-critical information to the user interface computer, accessing screen design information stored within the user interface computer, and using the safety-critical information and the screen design information to cause the user interface to display information related to the dialysis process.

[0053] In another aspect of the invention, methods of forming, for example, one or more hemodialysis systems are disclosed. In a further aspect of the invention, methods of using, for example, one or more hemodialysis systems are disclosed.

[0054] In yet another aspect, the present invention relates to a control architecture for the dialysis system, the control architecture comprising a user interface model layer, a therapy layer below the user interface model layer, and a machine layer below the therapy layer. The user interface model layer is configured to manage a state of a graphical user interface and receive input from the graphical user interface. The therapy layer is configured to execute a state machine that generates therapy commands based at least in part on the input from the graphical user interface. The machine layer is configured to provide commands to actuators based on the therapy commands.

[0055] Another aspect of the present invention relates to a method for disinfecting a fluid pathway of a dialysis system, the method including storing disinfection parameters, including a disinfection temperature and a disinfection time, in at least one storage medium, and further including circulating a fluid through the fluid pathway, monitoring the temperature of the fluid with each of a plurality of temperature sensors, and determining that disinfection of the fluid pathway is complete when 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.

[0056] Another aspect of the invention relates to at least one computer-readable medium encoded with instructions that, when executed by at least one processing device, perform a disinfection method for disinfecting a fluid pathway of a dialysis system. The method includes electronically receiving disinfection parameters including a disinfection temperature and a disinfection time. The method further includes controlling a plurality of actuators to circulate a fluid through the fluid pathway, 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 at or above the disinfection temperature for at least the disinfection time.

[0057] Another aspect of the present invention relates to a control method for controlling administration of an anticoagulant in a dialysis system, the method including the steps of storing, in at least one storage medium, an anticoagulant protocol including a maximum amount of anticoagulant, automatically administering anticoagulant according to the anticoagulant protocol, and inhibiting further administration of anticoagulant after determining that the maximum amount of anticoagulant has been administered.

[0058] Another aspect of the invention relates to at least one computer-readable medium encoded with instructions that, when executed by at least one processing device, perform a control method for controlling administration of anticoagulant in a dialysis system, the method including electronically receiving an anticoagulant protocol including a maximum amount of anticoagulant, controlling a plurality of actuators to administer anticoagulant in accordance with the anticoagulant protocol, and inhibiting further administration of anticoagulant after determining that the maximum amount of anticoagulant has been administered.

[0059] Another aspect of the invention relates to a method for determining a fluid level in a dialysate tank of a dialysis system, the method including tracking a first number of strokes that deliver fluid to the dialysate tank, tracking a second number of strokes that drain fluid from the dialysate tank, and determining the fluid level in the dialysate tank based at least in part on the first number of strokes, the second number of strokes, and the volume per stroke.

[0060] Another aspect of the present invention relates to a method for determining a fluid level in a dialysate tank of a dialysis system, the method including filling a reference chamber of known volume to a predetermined pressure and venting the reference chamber to the dialysate tank. The method further includes determining the pressure in the dialysate tank after venting the reference chamber to the dialysate tank. Additionally, the method includes determining the fluid level in the dialysate tank based, at least in part, on the determined pressure in the dialysate tank.

[0061] Another aspect of the present invention relates to a method for returning blood to a patient in the event of a power failure condition in a dialysis system that uses compressed air to drive pumps and / or valves during the dialysis process. The method includes a dialysis system having a dialysis device with a membrane separating a blood flow path from a dialysate flow path. The method includes identifying a power failure condition in the dialysis system. The method further includes, in response to identifying the power failure condition, releasing compressed air from a tank associated with the dialysis system. Additionally, the method includes using the released compressed air to increase the pressure in the dialysate flow path, thereby returning blood in the blood flow path to the patient.

[0062] Another aspect of the present invention relates to a method for returning extracorporeal blood to a patient in an extracorporeal treatment system in the event of a power outage using a compressed gas source. The extracorporeal treatment system includes a filter having a semipermeable membrane separating a blood flow path from an electrolyte solution flow path. The compressed gas is in communication with an electrolyte solution container via a valve, and the electrolyte solution container is in communication with the electrolyte solution flow path via a valve. The method includes, in response to termination of power to one or more electrically actuated valves controlling the distribution of the compressed gas or the distribution of the electrolyte solution flow in the extracorporeal treatment system, causing one or more first electrically actuated valves to open a first fluid path between the compressed gas and the electrolyte solution container, causing one or more second electrically actuated valves to open a second fluid path between the electrolyte solution container and the filter, causing one or more third electrically actuated valves to close an alternative fluid path of the electrolyte solution flow path if the alternative fluid path diverts the electrolyte solution from the filter, and using the compressed gas to increase the pressure of the electrolyte solution flow path, thereby returning blood in the blood flow path to the patient.

[0063] Another aspect of the present invention relates to a method for returning extracorporeal blood to a patient in an extracorporeal treatment system in the event of a power failure using a compressed gas source. The extracorporeal treatment system includes a filter having a semipermeable membrane separating a blood flow path from an electrolyte solution flow path. The compressed gas is in valved communication with an electrolyte solution container, and the electrolyte solution container is in valved communication with the electrolyte solution flow path. The method includes, in response to termination of electrical power to one or more electrically actuated valves that control distribution of the compressed gas or distribution of the electrolyte solution flow in the extracorporeal treatment system, causing the one or more electrically actuated valves to open a fluid path between the compressed gas and the electrolyte solution container, and using the compressed gas to cause a flow of electrolyte solution from the electrolyte solution container to the filter, thereby returning blood in the blood flow path to the patient.

[0064] Another aspect of the present invention relates to a pressure distribution module. In one embodiment, the pressure distribution module includes one or more manifold blocks; at least one gasket; one or more output ports; one or more supply lines; and at least one valve, wherein a first manifold block includes a surface having a plurality of channels formed therein, the channels being sealed to form fluid passages by pressing the first gasket against the channels with a rigid backing plate, the supply lines being formed as passages through the manifold block that pass under one or more of the channels, each supply line being connected to an independent source of air pressure or vacuum, and the valve being fluidly connected to at least one supply line and the output port via a hole in the manifold block that fluidly connects the one or more channels to the valve, the supply line, and the output port.

[0065] In an embodiment, a pressure distribution module comprises two or more manifold blocks; two or more gaskets; one or more output ports; one or more supply lines; and at least one valve, wherein a first manifold block includes a surface having a plurality of channels formed therein, and a second manifold block includes a first surface having a plurality of channels formed therein and an opposing generally smooth second surface, the channels on the first manifold block being sealed to form fluid passages by pressing one of the gaskets against the channels with the generally smooth second surface of the second manifold block, the supply lines being formed by passages through the manifold blocks that pass under at least some of the channels, each supply line being connected to an independent source of air pressure or vacuum when the module is configured in an operative configuration, and at least one valve being fluidly connected from one or more of the channels to at least one of the supply lines and to at least one output port via at least one hole that passes through the valve, the supply line, and the output port.

[0066] Another aspect of the present invention relates to a hemodialysis system. In one embodiment, the hemodialysis system includes a plurality of pneumatically actuated membrane pumps and valves for controlling the flow of blood and dialysate through a hemodialysis machine, the pumps and valves being driven by a pressure source having a first positive pressure, a pressure source having a second positive pressure less than the first positive pressure, or a pressure source having a negative pressure, wherein the pumps and valves in contact with blood in the extracorporeal circuit of the system are fluidly connected to the second positive or negative pressure source when the system is connected to a patient.

[0067] In an embodiment, the hemodialysis system includes a plurality of diaphragm-based reciprocating pumps; a plurality of diaphragm-based valves; and a pressure distribution module including a plurality of valves requiring power for operation and configured to provide pressurized fluid to operate the diaphragm-based reciprocating pumps and the diaphragm-based valves to control the flow of blood and dialysate within the hemodialysis system, the pressure distribution module configured to operate the pumps and valves to assume open or closed positions as needed to facilitate control of the system such that blood in the extracorporeal circuit of the system connected to a patient during operation can be pushed back to the patient in the event of a loss of power or control of the hemodialysis system.

[0068] Another aspect of the invention relates to a heater circuit for a dialysis unit. In one embodiment, the heater circuit includes a dialysate flow path carrying a flow of dialysate for use in the dialysis unit, a heater configured to heat dialysate in the dialysate flow path, a heater configured to sense a heater temperature of a portion of the heater, a pump for controllably moving fluid in the dialysate flow path, and a heater control circuit for controlling the heater using a first control loop to achieve a desired heater temperature by sending a heater control signal to control heater power, wherein one or more gains are used by the heater control circuit to generate the heater control signal, and the one or more gains vary based on an operating mode of the dialysis unit.

[0069] Another aspect of the invention relates to a dialysis unit including a field programmable gate array (FPGA). In an embodiment, the dialysis unit includes a dialysate flow circuit including a dialyzer; and a field programmable gate array (FPGA) that monitors at least the conductivity and temperature of dialysate in the dialysate flow circuit upstream of the dialyzer and that goes into a fail-safe state when the measured conductivity exceeds a value and / or falls outside a range of values, the value or range of values ​​varying for different treatment modes or for different patients.

[0070] In an embodiment, the dialysis unit includes: a dialysate flow circuit including a dialyzer and an ultrafiltration pump; and a field programmable gate array that monitors the amount of ultrafiltrate fluid drained from the patient during dialysis treatment by the dialysis unit by setting a given register to a first value, increasing the value of the register by a first incremental value with each pumping stroke of the ultrafiltration pump, and decreasing the value of the register by a second incremental value with each elapse of a predetermined time, the field programmable gate array entering a fail-safe state if the value of the register exceeds a predetermined maximum value.

[0071] In an embodiment, the dialysis unit includes a dialysate flow circuit including a dialysis machine; and an automatic computer processing device that verifies that a safety system mediated by a field programmable gate array (FPGA) is operating properly before treatment begins by exposing a sensor in a flow path in the dialysis unit to a temperature or conductivity outside a predetermined range of acceptable values, and that verifies that the FPGA safety system goes into a fail-safe state in response to a temperature or conductivity outside the predetermined range of acceptable values, and that resets the FPGA by writing to one or more registers of the FPGA within a predetermined time interval after verifying that the safety system is operating properly.

[0072] Another aspect of the invention relates to a method implemented by an operational set of processor-executable instructions configured to be executed by a computer processor. In an embodiment, the method includes the acts of determining whether a tablet is coupled to a base via a physical connection; establishing a first communications link between the tablet and the base via the physical connection; updating interface programs on the tablet and the base as needed via the first communications link; establishing a second communications link between the tablet and the base using the first communications link; and communicating data from the base to the tablet using the second communications link.

[0073] In an embodiment, the method includes the acts of communicating data between the tablet and the base as long as the link quality value exceeds a predetermined threshold; entering a headless state when the link quality value falls below the predetermined threshold; remaining in the headless state as long as the link quality value remains below the predetermined threshold; determining whether the link quality value has returned to a value above the predetermined threshold; and exiting the headless state if the link quality value has returned to a value above the predetermined threshold.

[0074] In an embodiment, the method includes the acts of communicating data between the tablet and the base as long as the link quality value exceeds a first predetermined threshold; entering a headless state when the link quality value falls below the first predetermined threshold; remaining in the headless state as long as the link quality value remains below a second predetermined threshold; determining whether the link quality value has increased to a value greater than the second predetermined threshold; and exiting the headless state if the link quality value exceeds the second predetermined threshold.

[0075] Another aspect of the invention relates to a pump system, which in an embodiment includes a rigid chamber wall; a rigid limiting structure; a flexible membrane attached to and sandwiched between the rigid chamber wall and the rigid limiting structure such that the flexible membrane and the rigid chamber wall together define a pump chamber and the flexible membrane and the rigid limiting structure together define a drive chamber, the rigid limiting structure being shaped and positioned to limit movement of the membrane and limit a maximum volume of the pump chamber; an inlet for directing flow through the rigid chamber wall into the pump chamber; an outlet for directing flow through the rigid chamber wall out of the pump chamber; and a drive system for alternately providing positive or negative pressure to the drive chamber, a controller that receives pressure information from the drive chamber pressure transducer and controls the valve mechanism with a valve control signal to apply a given pressure to the drive chamber with superimposed periodic variations, calculates a first cross correlation between the valve control signal and the drive chamber pressure, calculates a second cross correlation between the valve control signal and the drive chamber pressure offset by a quarter period, calculates a correlation coefficient by summing the squares of the first cross correlation value and the second cross correlation value, and uses the correlation coefficient when evaluating flow in the pump.

[0076] In an embodiment, the pump system comprises: a rigid chamber wall; a rigid limiting structure; a flexible membrane attached to and sandwiched between the rigid chamber wall and the rigid limiting structure such that the flexible membrane and the rigid chamber wall together define a pump chamber and the flexible membrane and the rigid limiting structure together define an actuation chamber, the rigid limiting structure being shaped and positioned to limit movement of the membrane and limit the maximum volume of the pump chamber; an inlet for directing flow through the rigid chamber wall into the pump chamber; and an inlet for directing flow through the rigid chamber wall out of the pump chamber. an outlet for directing the flow; a drive system that alternately provides positive or negative pressure to the drive chamber, the drive system comprising a tank containing a control fluid at either positive or negative pressure and a valve mechanism for controlling the flow of the control fluid between the drive chamber and the tank; a drive chamber pressure transducer for measuring the pressure in the drive chamber; and a controller that receives pressure information from the drive chamber pressure transducer and controls the valve mechanism via a valve control signal to apply a given pressure to the drive chamber with superimposed cyclical variations, the frequency of the superimposed cyclical variations being different for each of the reciprocating positive displacement pumps.

[0077] In some embodiments, the pump system includes a rigid chamber wall; a rigid limit structure; a flexible membrane attached to and sandwiched between the rigid chamber wall and the rigid limit structure, such that the flexible membrane and the rigid chamber wall together define a pump chamber and the flexible membrane and the rigid limit structure together define an actuation chamber, the rigid limit structure being shaped and positioned to limit movement of the membrane and limit the maximum volume of the pump chamber; an inlet for directing flow through the rigid chamber wall into the pump chamber; and an outlet for directing flow through the rigid chamber wall out of the pump chamber. a drive system that alternately provides positive or negative pressure to the drive chamber, the drive system comprising a tank containing a control fluid at either positive or negative pressure and a valve mechanism for controlling the flow of the control fluid between the drive chamber and the tank; a drive chamber pressure transducer for measuring the pressure in the drive chamber; and a controller that receives pressure information from the drive chamber pressure transducer and controls the valve mechanism with a valve control signal to apply a given pressure to the drive chamber with superimposed periodic variations, calculates a first cross-correlation between the valve control signal and the drive chamber pressure, and uses the first cross-correlation value when evaluating flow in the pump.

[0078] In an embodiment, the pump system comprises: a rigid chamber wall; a rigid limiting structure; a flexible membrane attached to and sandwiched between the rigid chamber wall and the rigid limiting structure such that the flexible membrane and the rigid chamber wall together define a pump chamber and the flexible membrane and the rigid limiting structure together define a drive chamber, the rigid limiting structure being shaped and positioned to limit movement of the membrane and limit a maximum volume of the pump chamber; an inlet for directing flow through the rigid chamber wall into the pump chamber; an outlet for directing flow through the rigid chamber wall out of the pump chamber; and a drive system for alternately providing positive or negative pressure to the drive chamber, the positive or negative pressure being and a valve mechanism for controlling the flow of the control fluid between the actuation chamber and the tank; an actuation chamber pressure transducer for measuring the pressure in the actuation chamber; and a controller that receives pressure information from the actuation chamber pressure transducer and controls the valve mechanism during a first period to complete a full stroke by moving a diaphragm from a position where it contacts a rigid limiting structure to a position where it contacts a rigid chamber wall, and records the value of a stroke parameter at the end of the full stroke, and during a subsequent period to complete a partial stroke by controlling the valve mechanism to move the diaphragm until the stroke parameter is a fraction of the full stroke value.

[0079] Another aspect of the invention relates to a method for performing hemodialysis using an ultrafiltration pump to control the volume of fluid removed from a patient. In an embodiment, the method includes the steps of: setting an ultrafiltration pump speed over a planned time period for hemodialysis to achieve a predetermined volume of fluid removed from the patient; periodically backflushing a predetermined volume of dialysate from a dialysate source through a dialyzer membrane into an extracorporeal blood circuit connected to the patient; and adjusting the ultrafiltration pump speed to remove the backflushed volume of fluid during the hemodialysis treatment.

[0080] Another aspect of the invention relates to a system for administering a dose of a drug to a patient whose vascular system is fluidly connected to an extracorporeal blood circuit including an arterial flow path for delivering fluid from the patient to a dialyzer and a venous flow path for delivering fluid from the dialyzer to the patient. In one embodiment, the system includes a drug vial fluidly connected to a drug pump in fluid communication with a primary fluid pump in the extracorporeal circuit via a valve; a first air bubble detector for detecting air bubbles in the arterial flow path; and drug pump valves and primary fluid pump inlet and outlet valves under the control of a controller for directing fluid flow from the dialyzer to the patient via either the arterial or venous flow path, wherein in a first configuration, the controller configures the valves to allow drug flow from the drug pump to the patient via the arterial flow path, and in a second configuration, when the controller receives a signal from the air bubble detector indicating the presence of one or more air bubbles in the arterial flow path, the controller configures the valves to allow drug flow from the drug pump to the patient via the venous flow path.

[0081] Other advantages and novel features of the present invention will become apparent from the following description of various embodiments of the present invention when considered in conjunction with the accompanying drawings. The embodiments are not limited to those described below. The specification and any cited documents may contain conflicts or inconsistencies, but the specification shall prevail. Two or more cited documents may contain conflicts or inconsistencies with each other, but the later-published document shall prevail.

[0082] Non-limiting embodiments of the present invention are disclosed with reference to the accompanying drawings, which are not intended to be drawn to scale. In the drawings, identical or nearly identical elements are typically each designated by a single reference numeral. For clarity, not every element is designated by a reference numeral in every drawing, and not every element of every embodiment of the present invention is shown to enable one skilled in the art to understand the present invention. [Brief explanation of the drawings]

[0083] [Figure 1] 1 is a schematic diagram showing a hemodialysis system. [Figure 2A]1A-1D are high-level schematic diagrams illustrating various embodiments of a dialysis system. [Figure 2B] 1A-1D are high-level schematic diagrams illustrating various embodiments of a dialysis system. [Figure 3A] Schematic diagram showing example fluids in a dialysis system. [Figure 3B] Schematic diagram showing example fluids in a dialysis system. [Figure 4A] 1 is a schematic diagram illustrating a blood flow circuit used in one embodiment of a hemodialysis system. [Figure 4B] 1 is a schematic diagram illustrating a blood flow circuit used in one embodiment of a hemodialysis system. [Figure 4C] FIG. 4B is a perspective view of the air trap of FIG. 4A. [Figure 4D] Side view of the air trap of Figure 4A. [Figure 5] FIG. 1 is a schematic diagram illustrating a balancing circuit used in one embodiment of a hemodialysis system. [Figure 6] 1 is a schematic diagram showing a directing circuit used in a hemodialysis system. [Figure 7A] 1 is a schematic diagram showing a mixing circuit used in a hemodialysis system. [Figure 7B] 1 is a schematic diagram showing a mixing circuit used in a hemodialysis system. [Figure 8A] FIG. [Figure 8B] FIG. [Figure 8C] FIG. [Figure 9] 10A and 10B are cross-sectional views illustrating valves incorporated into an embodiment of a fluid-control cassette. [Figure 10] 10 is a cross-sectional view of a pod pump incorporated into an embodiment of a fluid control cassette. [Figure 11A] Schematic diagrams showing various pneumatic control systems for pod pumps. [Figure 11B] Schematic diagrams showing various pneumatic control systems for pod pumps. [Figure 12] Graph showing how the pressure applied to the pod pump is managed. [Figure 13A] FIG. 10 illustrates the detection of an occlusion. [Figure 13B] FIG. 10 illustrates the detection of an occlusion. [Figure 14] FIG. 4 is a diagram showing a control algorithm in one embodiment. [Figure 15] FIG. 1 illustrates a standard discrete PI regulator for a controller in one embodiment. [Figure 16] FIG. 1 illustrates a dual housing cassette configuration in one embodiment. [Figure 17A] FIG. 10 is a diagram of priming parts of a system in one embodiment of the invention. [Figure 17B] FIG. 10 is a diagram of priming parts of a system in one embodiment of the invention. [Figure 17C] FIG. 10 is a diagram of priming parts of a system in one embodiment of the invention. [Figure 18A] FIG. 1 illustrates the flow rate of dialysate from the dialysate tank through the dialyzer and out the drain in one embodiment of the invention. [Figure 18B] FIG. 1 illustrates the flow rate of dialysate from the dialysate tank through the dialyzer and out the drain in one embodiment of the invention. [Figure 19] FIG. 10 illustrates emptying of the dialysate tank in another embodiment of the invention. [Figure 20] FIG. 10 illustrates purging of the system with air at the end of a procedure in one embodiment of the invention. [Figure 21A] FIG. 10 illustrates the pumping of air by an anticoagulant pump in accordance with another embodiment of the invention. [Figure 21B] FIG. 10 illustrates the pumping of air by an anticoagulant pump in accordance with another embodiment of the invention. [Figure 21C] FIG. 10 illustrates the pumping of air by an anticoagulant pump in accordance with another embodiment of the invention. [Figure 22A] FIG. 10 illustrates an integrity test in an embodiment of the invention. [Figure 22B] FIG. 10 illustrates an integrity test in an embodiment of the invention. [Figure 22C] FIG. 10 illustrates an integrity test in an embodiment of the invention. [Figure 22D] FIG. 10 illustrates an integrity test in an embodiment of the invention. [Figure 23] FIG. 10 shows a recirculation flow path in another embodiment of the invention. [Figure 24A] FIG. 10 illustrates priming of a system with dialysate in accordance with yet another embodiment of the invention. [Figure 24B] FIG. 10 illustrates priming of a system with dialysate in accordance with yet another embodiment of the invention. [Figure 24C] FIG. 10 illustrates priming of a system with dialysate in accordance with yet another embodiment of the invention. [Figure 24D] FIG. 10 illustrates priming of a system with dialysate in accordance with yet another embodiment of the invention. [Figure 25] FIG. 10 illustrates priming of an anticoagulant pump in accordance with yet another embodiment of the invention. [Figure 26A] FIG. 10 illustrates the removal of dialysate from the blood flow circuit in one embodiment of the invention. [Figure 26B] FIG. 10 illustrates the removal of dialysate from the blood flow circuit in one embodiment of the invention. [Figure 26C] FIG. 10 illustrates the removal of dialysate from the blood flow circuit in one embodiment of the invention. [Figure 26D] 10A-10C illustrate the removal of dialysate from the blood flow circuit in one embodiment of the invention. [Figure 26E] FIG. 10 illustrates the removal of dialysate from the blood flow circuit in one embodiment of the invention. [Figure 26F] FIG. 10 illustrates the removal of dialysate from the blood flow circuit in one embodiment of the invention. [Figure 27A] FIG. 10 illustrates the delivery of anticoagulant pills to a patient in another embodiment of the invention. [Figure 27B] FIG. 10 illustrates the delivery of anticoagulant pills to a patient in another embodiment of the invention. [Figure 27C] FIG. 10 illustrates the delivery of anticoagulant pills to a patient in another embodiment of the invention. [Figure 28] 1 illustrates solution injection in one embodiment of the invention. [Figure 29A] Schematic showing how an emergency cleaning process can be carried out. [Figure 29B]Schematic showing how an emergency cleaning process can be carried out. [Figure 30A] 10A and 10B are isometric and plan views of the outer top plate of an embodiment of the cassette. [Figure 30B] 10A and 10B are isometric and plan views of the outer top plate of an embodiment of the cassette. [Figure 30C] 10A and 10B are isometric and plan views of the inner top plate of an embodiment of the cassette. [Figure 30D] 10A and 10B are isometric and plan views of the inner top plate of an embodiment of the cassette. [Figure 30E] FIG. 10 is a side view of the top plate of the exemplary cassette. [Figure 31A] 10A and 10B are isometric and top views of the fluid side of an embodiment of a cassette midplate; [Figure 31B] 10A and 10B are isometric and top views of the fluid side of an embodiment of a cassette midplate; [Figure 31C] 10A and 10B are isometric and top views of the air side of the midplate of an exemplary cassette; [Figure 31D] 10A and 10B are isometric and top views of the air side of the midplate of an exemplary cassette; [Figure 32A] 10A and 10B are isometric and plan views of the inside of the bottom plate of an embodiment of the cassette. [Figure 32B] 10A and 10B are isometric and plan views of the inside of the bottom plate of an embodiment of the cassette. [Figure 32C] 10A and 10B are isometric and plan views of the exterior of the bottom plate of an embodiment of a cassette. [Figure 32D] 10A and 10B are isometric and plan views of the exterior of the bottom plate of an embodiment of a cassette. [Figure 32E] FIG. 10 is a side view of the bottom plate of the exemplary cassette. [Figure 33A] FIG. 10 is a top view of an assembled cassette with vials attached according to an embodiment. [Figure 33B] FIG. 10 is a bottom view of an assembled cassette with vials attached according to an embodiment. [Figure 33C] 10 is an exploded view of an assembled cassette with vials attached in accordance with an embodiment. FIG. [Figure 33D] 10 is an exploded view of an assembled cassette with vials attached in accordance with an embodiment. FIG. [Figure 34A] FIG. 10 is an isometric bottom view of an exemplary embodiment of a cassette midplate. [Figure 34B] FIG. 10 is an isometric top view of an exemplary embodiment of a cassette midplate. [Figure 34C] FIG. 10 is an isometric bottom view of an exemplary embodiment of a cassette midplate. [Figure 34D] FIG. 10 is a side view of the midplate of the cassette in accordance with an embodiment. [Figure 35A] 10A and 10B are isometric and plan views of the top plate of an embodiment of a cassette. [Figure 35B] 10A and 10B are isometric and plan views of the top plate of an embodiment of a cassette. [Figure 35C] 1 is an isometric view of the top plate of an embodiment of the cassette. [Figure 35D] 1 is an isometric view of the top plate of an embodiment of the cassette. [Figure 35E] FIG. 10 is a side view of the top plate of the exemplary cassette. [Figure 36A] FIG. 10 is an isometric bottom view of an embodiment of a bottom plate of a cassette according to an embodiment. [Figure 36B] FIG. 10 is an isometric bottom view of an embodiment of a bottom plate of a cassette according to an embodiment. [Figure 36C] FIG. 10 is an isometric plan view of the bottom plate of an embodiment of the cassette. [Figure 36D] FIG. 10 is an isometric plan view of the bottom plate of an embodiment of the cassette. [Figure 36E] FIG. 10 is a side view of the bottom plate of the exemplary cassette. [Figure 37] FIG. 37 is an isometric front view of the drive side of the midplate of a cassette with valves shown in an embodiment corresponding to FIG. 36; [Figure 38A] Schematic diagram showing the outer top plate of an embodiment of a cassette. [Figure 38B] 10 is a schematic diagram showing the interior top plate of an embodiment of a cassette. [Figure 38C]FIG. 10 is a side view of the top plate of the cassette according to the embodiment. [Figure 39A] 10 is a schematic diagram illustrating the fluid side of the midplate of an embodiment of a cassette. [Figure 39B] FIG. 10 is a front view of the air side of the midplate of the cassette according to the embodiment; [Figure 39C] FIG. 10 is a side view of the midplate of the cassette according to the embodiment. [Figure 40A] FIG. 10 is a side view of the interior of the bottom plate of the cassette in an embodiment. [Figure 40B] 10 is a schematic diagram showing the outside of the bottom plate of an embodiment of the cassette. [Figure 40C] FIG. 10 is a side view of the midplate of the cassette according to the embodiment. [Figure 41A] 10A and 10B are isometric and front views of an outer top plate of an embodiment of a cassette; [Figure 41B] 10A and 10B are isometric and front views of an outer top plate of an embodiment of a cassette; [Figure 41C] 10A and 10B are isometric and front views of the interior top plate of an embodiment of a cassette. [Figure 41D] 10A and 10B are isometric and front views of the interior top plate of an embodiment of a cassette. [Figure 41E] FIG. 10 is a side view of the top plate of the cassette according to the embodiment. [Figure 42A] 10A and 10B are isometric and front views of the fluid side of an embodiment of a cassette midplate; [Figure 42B] 10A and 10B are isometric and front views of the fluid side of an embodiment of a cassette midplate; [Figure 42C] 10A and 10B are isometric and front views of the air side of the midplate of an exemplary cassette; [Figure 42D] 10A and 10B are isometric and front views of the air side of the midplate of an exemplary cassette; [Figure 42E] FIG. 10 is a side view of the midplate of the cassette according to the embodiment. [Figure 43A] 10A and 10B are isometric and front views of the interior side of the bottom plate of an exemplary cassette; [Figure 43B] 10A and 10B are isometric and front views of the interior side of the bottom plate of an exemplary cassette; [Figure 43C] 10A and 10B are isometric and front views of the exterior of the bottom plate of the cassette in an embodiment. [Figure 43D] 10A and 10B are isometric and front views of the exterior of the bottom plate of the cassette in an embodiment. [Figure 43E] FIG. 10 is a side view of the bottom plate of the cassette according to the embodiment. [Figure 44A] FIG. 10 is a plan view showing an assembled cassette in the embodiment. [Figure 44B] FIG. 10 is a bottom view of an assembled cassette according to an embodiment. [Figure 44C] FIG. 10 is an exploded view of an assembled cassette according to an embodiment. [Figure 44D] FIG. 10 is an exploded view of an assembled cassette according to an embodiment. [Figure 45] FIG. 1 is a cross-sectional view of an assembled cassette system according to an embodiment. [Figure 46A] FIG. 1 is a front view showing an assembled cassette system according to an embodiment. [Figure 46B] 1 is an isometric view of an assembled cassette system according to an embodiment. [Figure 46C] 1 is an isometric view of an assembled cassette system according to an embodiment. [Figure 46D] FIG. 1 is an exploded view of an assembled cassette system according to an embodiment. [Figure 46E] FIG. 1 is an exploded view of an assembled cassette system according to an embodiment. [Figure 47A] 1 is an isometric view of a pod of a cassette system according to an embodiment; [Figure 47B] 1 is an isometric view of a pod of a cassette system according to an embodiment; [Figure 47C] FIG. 2 is a side view showing a pod of the cassette system according to the embodiment. [Figure 47D] 1 is an isometric view of one half of a pod of a cassette system according to an embodiment. [Figure 47E]1 is an isometric view of one half of a pod of a cassette system according to an embodiment. [Figure 48A] 10A and 10B show images of the membrane of a pod of a cassette system in an embodiment. [Figure 48B] 10A and 10B show images of the membrane of a pod of a cassette system in an embodiment. [Figure 49] FIG. 2 is an exploded view showing a pod of the cassette system according to the embodiment. [Figure 50A] FIG. 10 is an exploded view of the fluid lines of the check valve of the cassette system in one embodiment. [Figure 50B] FIG. 10 is an exploded view of the fluid lines of the check valve of the cassette system in one embodiment. [Figure 50C] 1 is an isometric view of an embodiment of the fluid lines of a cassette system. [Figure 51A] FIG. 1 is a schematic diagram illustrating fluid flow paths of an integrally formed cassette system in one embodiment. [Figure 51B] FIG. 1 is a schematic diagram illustrating fluid flow paths of an integrally formed cassette system in one embodiment. [Figure 52A] 1A-1C are various schematic diagrams illustrating blocks for connecting pneumatic tubes to a manifold in a system according to one embodiment of the present invention. [Figure 52B] 1A-1C are various schematic diagrams illustrating blocks for connecting pneumatic tubes to a manifold in a system according to one embodiment of the present invention. [Figure 52C] 1A-1C are various schematic diagrams illustrating blocks for connecting pneumatic tubes to a manifold in a system according to one embodiment of the present invention. [Figure 52D] 1A-1C are various schematic diagrams illustrating blocks for connecting pneumatic tubes to a manifold in a system according to one embodiment of the present invention. [Figure 52E] 1A-1C are various schematic diagrams illustrating blocks for connecting pneumatic tubes to a manifold in a system according to one embodiment of the present invention. [Figure 52F] 1A-1C are various schematic diagrams illustrating blocks for connecting pneumatic tubes to a manifold in a system according to one embodiment of the present invention. [Figure 53]FIG. 10 is a schematic diagram showing a sensor manifold according to another example. [Figure 54] FIG. 54 is a diagram showing the flow paths within the sensor manifold shown in FIG. 53. [Figure 55] FIG. 54 is a side view of the sensor manifold shown in FIG. 53. [Figure 56A] 56B is a cross-sectional view of the sensor manifold shown in FIG. 53 taken along line AA in FIG. 56B. [Figure 56B] FIG. 54 is a front view showing the sensor manifold shown in FIG. 53. [Figure 57] FIG. 54 is an exploded view of the sensor manifold shown in FIG. 53. [Figure 58] 54 shows the edge connector of the printed circuit board and media corresponding to the sensor manifold shown in FIG. 53. [Figure 59] Fluid design diagram of a hemodialysis system. [Figure 60] 1 is a perspective view of an embodiment of a combined user interface and treatment device. [Figure 61] 61 is a schematic diagram showing the hardware configuration of each of the display unit and user interface unit shown in FIG. 60. [Figure 62] 62 is a schematic diagram illustrating software processes that may be executed on the automation computer and user interface computer shown in FIG. 61. [Figure 62A] 63 is a schematic diagram illustrating the interaction of the software processes shown in relation to FIG. 62. [Figure 62B] Schematic diagram showing an alternative hardware configuration for the dialysis unit of Figure 61, including a hardware interface board with a field programmable gate array (FPGA) safety system. [Figure 63] Schematic diagram showing the flow of information between the hardware and software components of the user interface computer and the automation computer. [Figure 64] 64 is a schematic diagram illustrating a hierarchical state machine (HSM) that may be used in the UI controller shown in FIG. 63. [Figure 65]62A-62C are schematic diagrams illustrating normal and alarm screen displays that may be displayed on the user interface shown in FIG. 61. [Figure 66] Schematic diagram showing how the Therapy Layer interfaces with other layers such as the Machine Layer and the User Interface Model Layer. [Figure 67] Schematic diagram showing an example implementation of the machine layer shown in Figure 66. [Figure 67A-1] Schematic diagram showing an example implementation of dialyzer impedance clearance rate manipulation. [Figure 67A-2] Schematic diagram showing an example implementation of dialyzer impedance clearance rate manipulation. [Figure 67B] Schematic diagram showing an example of implementation of dialysate circulation operation. [Figure 67C] Schematic showing an example implementation of the heparin vial linkage test procedure. [Figure 67D] Schematic diagram showing an example implementation of a heparin administration operation. [Figure 67E] Schematic diagram showing an example implementation of a tank draining operation. [Figure 68-1] Schematic diagram showing an example implementation of the recycling preparation application. [Figure 68-2] Schematic diagram showing an example implementation of the recycling preparation application. [Figure 69A] Schematic showing an example implementation of the Blood Path Cleaning application. [Figure 69B] Schematic showing an example implementation of the Blood Path Cleaning application. [Figure 70A] Schematic showing an example implementation of a disinfection application. [Figure 70B] Schematic showing an example implementation of a disinfection application. [Figure 71] Schematic showing an example implementation of an endotoxin cleanup application. [Figure 72] Schematic diagram showing an example implementation of a treatment preparation application. [Figure 73A] Schematic diagram showing an example implementation of the Patient Connect application. [Figure 73B] Schematic diagram showing an example implementation of the Patient Connect application. [Figure 73C]Schematic diagram showing an example implementation of the Patient Connect application. [Figure 73D] Schematic diagram showing an example implementation of the Patient Connect application. [Figure 74A] Schematic diagram showing an example implementation of a dialysis application. [Figure 74B] Schematic diagram showing an example implementation of a dialysis application. [Figure 75A-1] Schematic showing an example implementation of a solvent injection application. [Figure 75A-2] Schematic showing an example implementation of a solvent injection application. [Figure 75B] Schematic showing an example implementation of a solvent injection application. [Figure 75C] Schematic showing an example implementation of a solvent injection application. [Figure 75D] Schematic showing an example implementation of a solvent injection application. [Figure 75E] Schematic showing an example implementation of a solvent injection application. [Figure 76A] 1 is a schematic diagram illustrating an example implementation of a rinseback application. [Figure 76B-1] 1 is a schematic diagram illustrating an example implementation of a rinseback application. [Figure 76B-2] 1 is a schematic diagram illustrating an example implementation of a rinseback application. [Figure 76C] 1 is a graph showing ultrafiltrate fluid flow in one implementation of a hemodialysis machine. [Figure 76D] 10 is a graph showing ultrafiltrate fluid flow, including periodic backflushing of fluid across the dialyzer membrane, in another implementation of the hemodialysis machine. [Figure 76E] 1 is a graph showing ultrafiltration fluid flow during hemodialysis, including the additional infusion or withdrawal of fluid from the patient. [Figure 76F] 10 is a screen diagram for displaying on a graphical user interface to summarize the results of hemodialysis treatment. [Figure 77] Schematic diagram showing an example implementation of a sampling application. [Figure 78A] FIG. 1 is a schematic diagram showing an example implementation of a part replacement application. [Figure 78B] FIG. 1 is a schematic diagram showing an example implementation of a part replacement application. [Figure 78C] FIG. 1 is a schematic diagram showing an example implementation of a part replacement application. [Figure 79A] Schematic showing an example implementation of a chemical mounting application. [Figure 79B] Schematic showing an example implementation of a chemical mounting application. [Figure 80] FIG. 1 is a diagram showing the pathway between the pressurized air tank and the dialysate tank in a hemodialysis system. [Figure 81] FIG. 1 is a fluidic schematic diagram of a hemodialysis system showing the blood flow path and the dialysate flow path used to measure the clearance rate of the dialyzer in an embodiment of the present invention. [Figure 82] 10 is a plot of measured and modeled conductivity data versus pump stroke number used in determining the cleaning rate of a dialysis machine in accordance with an embodiment of the present invention. [Figure 83] A plot relating the dialyzer parameter K, determined from data such as that shown in Figure 82, to measured urea clearance. [Figure 84] Schematic diagram of a balancing circuit including a balancing chamber and associated blood leak sensor. [Figure 85] FIG. 10 is a cross-sectional front view of an embodiment of a balance chamber and blood leak sensor. [Figure 86] FIG. 86 is a bottom view of the embodiment of FIG. 85. [Figure 87] FIG. 86 is a lower left perspective view of the embodiment of FIG. 85. [Figure 88] FIG. 2 is a perspective view of the blood leakage sensor bracket in this embodiment. [Figure 89] FIG. 1 is a schematic diagram of an example dialysis system with an air trap and accumulator in the water supply line. [Figure 90] FIG. 2 is a front view of the air trap in the embodiment. [Figure 91] Underside view of the air trap of Figure 90. [Figure 92] 91 is a cross-sectional front view of the air trap of FIG. [Figure 93]FIG. 2 is a front view of the accumulator according to the embodiment. [Figure 94] Underside view of the accumulator of Figure 93. [Figure 95] 94 is a cross-sectional front view of the air trap of FIG. 93; [Figure 96] FIG. 94 is an upper left front perspective view of the air trap of FIG. 93; [Figure 97] FIG. 2 is a plan view of the cassette system according to the embodiment. [Figure 98] Rear view of the cassette system of Figure 97. [Figure 99] FIG. 98 is a right side view of the cassette system of FIG. 97. [Figure 100] FIG. 98 is a top right rear perspective view of the cassette system of FIG. 97; [Figure 101A] 1 is an isometric view of the front of a pressure dispense module according to an embodiment of the present invention. [Figure 101B] 1 is an isometric view of the rear of a pressure distribution module according to an embodiment of the present invention. [Figure 102] 102 is an isometric view of left and right interface blocks for use with the pressure distribution module of FIG. 101; [Figure 103] 102 is an exploded view showing how the interface block is secured to the pressure distribution module of FIG. 101; [Figure 104] 1 is a detailed isometric view of the rear of a pressure dispense module in accordance with an embodiment of the present invention. [Figure 105] FIG. 2 is an exploded view of an embodiment of a multi-part air manifold. [Figure 106] Isometric view showing the flow channels of the end manifold block. [Figure 107] FIG. 10 is an exploded view of an alternative embodiment of a multi-part air manifold. [Figure 108] FIG. 10 is an exploded view of another alternative embodiment of a multi-part air manifold. [Figure 109] Isometric view of the pressure distribution module showing the variable valve and pressure sensor PCB. [Figure 110] Isometric view of the pressure distribution module showing the cartridge / valve and pressure supply attachments. [Figure 111A]Isometric view showing details of the mid-manifold block. [Figure 111B] Isometric view showing details of the mid-manifold block. [Figure 111C] Isometric view showing details of the mid-manifold block. [Figure 111D] Isometric view showing details of the mid-manifold block. [Figure 112] 1 is a schematic diagram of an exemplary pod pump with a fluid management system. [Figure 113] Schematic diagram of air delivery in a blood cassette. [Figure 114] Schematic of air delivery in the internal dialysate cassette. [Figure 115] Schematic diagram of air delivery in the external dialysate cassette. [Figure 116] Schematic diagram of air feeding in a mixing cassette. [Figure 117] Schematic of air delivery in the occluder. [Figure 118] Schematic diagram of the flow in the blood cassette. [Figure 119] Schematic of the flow in the internal dialysate cassette. [Figure 120] Schematic of the flow in the external dialysate cassette. [Figure 121] Schematic of the flow in the mixing cassette. [Figure 122] 1 is a schematic representation of a directing circuit that may be used in a hemodialysis system. [Figure 123A] Schematic diagram of the heater temperature control loop. [Figure 123B] Schematic of a heater temperature control loop nested within a fluid temperature control loop. [Figure 123C] Schematic diagram of the heater power control loop. [Figure 124] 10 is a flowchart illustrating a method for communicating between a tablet and a base in accordance with an embodiment of the present disclosure. [Figure 125] 10 is a flowchart illustrating a method for communicating between a tablet and a base in accordance with an embodiment of the present disclosure. [Figure 126]10 is a flowchart illustrating a method for communicating between a tablet and a base in accordance with an embodiment of the present disclosure. [Figure 127] 10 is a flowchart illustrating a method for communicating between a tablet and a base in accordance with an embodiment of the present disclosure. [Figure 128] 10 is a flowchart illustrating a method for communicating between a tablet and a base in accordance with an embodiment of the present disclosure. [Figure 129] 10 is a flowchart illustrating a method for communicating between a tablet and a base in accordance with an embodiment of the present disclosure. [Figure 130] Plot of simulated valve command and pressure response used in cross-correlation calculations. [Figure 131] Plot of an exemplary curve from a cross-correlation calculation. [Figure 132] Simulation plot of valve command and pressure response with varying phase angle between command and pressure. [Figure 133] Plot of cross-correlation results based on simulation of valve command and response including phase shift. [Figure 134] Pressure and cross correlation plots from the fill and delivery strokes. [Figure 135] Pressure and cross-correlation plots from the fill and delivery strokes in the presence of occlusion. [Figure 136] Schematic of a pressure-driven membrane pump actuated by a two-way valve. [Figure 137] Plot of valve actuation and resulting pump pressure during the delivery stroke. [Figure 138] Plot of pump pressure and integrated pressure change while the valve is closed for the delivery stroke. [Figure 139] Plot of pump pressure and integrated pressure change while the valve is closed for the fill stroke. [Figure 140] Schematic of a pressure-driven membrane pump actuated by a two-way valve. [Figure 141] FIG. 1 is a cutaway view of a water inlet module used in a hemodialysis machine. [Figure 142]FIG. 141 is a perspective view of the water inlet module. [Figure 143] 142 shows a water sensor used in the water inlet module of FIG. 141. [Figure 144] 2 is a diagram showing a location for the water inlet module of FIG. 1 in a hemodialysis machine. [Figure 145A] FIG. 1 is a state diagram illustrating 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 present disclosure. [Figure 145B] FIG. 1 is a state diagram illustrating 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 present disclosure. DETAILED DESCRIPTION OF THE INVENTION

[0084] The present invention relates to hemodialysis systems and similar dialysis systems, including various systems and methods that enable hemodialysis to be performed more efficiently, easily, and / or at lower cost. In an embodiment of the present invention, a novel fluid circuit for fluid flow is shown. In an embodiment, the hemodialysis system includes a blood flow path and a dialysate flow path, the dialysate flow path including one or more balancing circuits, mixing circuits, and / or directing circuits. In an embodiment, dialysate pretreatment by the mixing circuit is separate from the patient's dialysis. In an embodiment, the circuit is at least partially contained within one or more cassettes, optionally interconnected with conduits, pumps, etc. In an embodiment, the fluid circuit and / or the various fluid flow paths are at least partially spatially and / or thermally isolated from the electrical components of the hemodialysis system. In an embodiment, a gas supply is provided in communication with the dialysate flow path and / or the dialyzer. When activated, the gas supply can urge the dialysate through the dialyzer and blood in the blood flow path back into the patient's body. The system is useful, for example, in emergency situations (e.g., power outages) when it is desirable to return as much blood as possible to the patient. In another aspect of the invention, the hemodialysis system further includes one or more fluid treatment devices, such as pumps, valves, mixers, etc., that can be actuated using a control fluid, such as air. In some embodiments, the control fluid is delivered to the fluid treatment devices using a removable external pump or other device. In some embodiments, the one or more fluid treatment devices are generally rigid (e.g., have a spherical shape), and optionally include a septum within the device that separates the device into a first and second compartment.

[0085] Various aspects of the present invention are directed to novel hemodialysis systems, such as hemofiltration systems, hemodiafiltration systems, and plasma exchange systems. Although various systems and methods are disclosed relating to hemodialysis, the various systems and methods may be applicable to other dialysate systems and / or extracorporeal systems capable of treating other bodily fluids, such as blood or plasma.

[0086] As described above, a hemodialysis system typically includes a blood flow path and a dialysate flow path. It should be noted that fluid flow within the flow path is not necessarily linear; there may be any number of "branches" within the flow path, with the fluid flowing from the inlet to the outlet. Examples of such branches are described in detail below. In the blood flow path, blood is drawn from the patient and passes through the dialyzer before being returned to the patient. The dialyzer processes the blood, and waste molecules (e.g., urea, creatinine, etc.) and water pass from the blood through the dialyzer and into the dialysate. The dialysate passes through the dialyzer via the dialysate flow path. In various embodiments, blood is drawn from the patient through two lines (e.g., an arterial line and a venous line, i.e., "two-needle" flow), or in some cases, blood is drawn from the patient and returned to the patient through the same needle (e.g., both lines are provided within the same needle, i.e., "single-needle" flow). In yet another example, a "Y" or "T" branch is used. Here, blood is pumped from and returned to the patient through a patient connection that has two branches (one for pumping blood and one for returning blood). The patient may be any subject requiring hemodialysis or a similar treatment, but the patient is typically a human. However, hemodialysis may also be performed on non-human subjects, such as dogs, cats, and monkeys.

[0087] Fresh dialysate is prepared in the dialysate flow path and passed through the dialyzer to treat blood from the blood flow path. The dialysate is further equalized within the dialyzer (i.e., the pressure between the dialysate and the blood is equalized) for treatment of the blood, i.e., the pressure of the dialysate passing through the dialyzer closely matches, typically exactly, the blood pressure passing through the dialyzer, or in some embodiments, within at least about 1% or about 2% of the blood pressure. After passing through the dialyzer, the used dialysate contains waste molecules (described below). In some embodiments, the dialysate is heated using a suitable heater, such as an electrical resistance heater, prior to treatment of the blood in the dialyzer. The dialysate is further filtered, for example, using an ultrafilter to remove contaminants, infectious organisms, and debris. The ultrafilter has a mesh size selected to prevent the passage of the above types of particles. For example, the mesh size may be about 0.3 micrometers or less, about 0.2 micrometers or less, about 0.1 micrometers or less, or about 0.05 micrometers or less. Dialysates are used to draw waste molecules (e.g., urea, creatinine, ions such as potassium, phosphate, etc.) and water from the blood into the dialysate through osmosis. Dialysates are well known to those skilled in the art.

[0088] Dialysis fluid typically contains various ions, such as potassium and calcium, similar to their natural concentrations in healthy blood. In some embodiments, the dialysate typically contains a higher concentration of sodium bicarbonate than that found in normal blood. Dialysis fluid is typically prepared by mixing one or more ingredients, namely, "acid" (including various types of acetic acid, glucose, NaCl, CaCl, KCl, MgCl, etc.), sodium bicarbonate (NaHCO3), and / or sodium chloride (NaCl), with water from a water supply. Preparation of dialysis fluid, including using appropriate concentrations of salts, osmolality, pH, etc., is well known to those skilled in the art. As described in more detail below, dialysis fluid need not be prepared to the same concentration as the dialysis fluid used to treat blood. For example, dialysis fluid can be formed simultaneously with or prior to dialysis and contained within a dialysis fluid storage container or the like.

[0089] Within a dialysis machine, the dialysate and blood typically do not physically contact each other but are separated by a semipermeable membrane. Semipermeable membranes are typically made of polymers such as cellulose, polyarylethersulfone, polyamide, polyvinylpyrrolidone, polycarbonate, or polyacrylonitrile. These membranes allow ions and small molecules (e.g., urea, water, etc.) to pass through the membrane, but do not allow bulky particles to pass through or convect through during blood treatment. In some instances, larger particles, such as beta-2 microglobulin, also pass through the membrane.

[0090] The dialysate and blood do not physically contact each other within the dialyzer, but are typically separated by a semipermeable membrane. Dialysis machines typically employ a "shell-and-tube" design, consisting of multiple separate tubes or fibers formed from the semipermeable membrane (through which the blood flows) and a larger "shell" (or in some embodiments, the reverse) through which the dialysate flows and which surrounds the tubes or fibers. In some embodiments, the flow of dialysate and blood through the dialyzer may be countercurrent or cocurrent. Dialysis machines are well known to those skilled in the art and are available from a number of different commercial sources.

[0091] In one embodiment, the dialysate flow path is separated into one or more circuits, i.e., a balancing circuit, a mixing circuit, and / or a directing circuit. With respect to fluid flow, it should be noted that circuits need not be fluid-separated, and fluids may flow into and out of fluid circuits. Similarly, fluids may flow sequentially from one fluid circuit to another when the fluid circuits are interconnected or interconnected. As used herein, "fluid" refers to fluids having characteristics of a fluid, including, but not limited to, gases such as air, liquids such as water, aqueous solutions, blood, dialysate, etc.

[0092] A fluid circuit is typically a distinct module that accepts any number of fluid inputs and, in some embodiments, performs one or more tasks in response to the fluid inputs before appropriately outputting the fluid. As described below in certain embodiments of the present invention, the fluid circuit may be configured as a cassette. In particular, the dialysate flow path includes a balancing circuit, a directing circuit, and a mixing circuit. In another embodiment, the blood flow path includes a blood flow circuit. Within the balancing circuit, dialysate is directed through the balancing circuit, and a pump acts on the dialysate to balance the pressure of the dialysate passing through the dialyzer with the pressure of the blood passing through the dialysate, as described above. Similarly, within the directing circuit, fresh dialysate moves from the mixing circuit to the balancing circuit, and used dialysate moves from the balancing circuit to drain. Within the mixing circuit, materials and water mix to form fresh dialysate. The blood flow circuit is used to draw blood from the patient, pass it through the dialyzer, and return it to the patient. These circuits are described in more detail below.

[0093] FIG. 2A is a high-level schematic diagram illustrating an example hemodialysis system having the fluid circuits described above. It shows a dialysis system 5 including a blood flow circuit 10 through which blood travels from a patient to a dialyzer 14 and through which treated blood passes back to the patient. The hemodialysis system in this example also includes a balancing circuit, or inner dialysate circuit 143, which pumps dialysate after the dialysate has passed through an ultrafilter 73 and then through the dialyzer 14. Used dialysate returns from the dialyzer 14 to the balancing circuit 143. A directing circuit, or outer dialysate circuit 142, processes unused dialysate before it passes through the ultrafilter 73. A mixing circuit 25 prepares dialysate using various ingredients 49 and water during and / or prior to dialysis, e.g., on demand. The directing circuit 142 also receives water from a water supply 30 and moves the water to the mixing circuit 25 for dialysate preparation. Directing circuit 142 also receives spent dialysate from balancing circuit 143 and transfers it out of system 5 through drain 31. A conduit 67 is also shown in dashed lines connecting blood flow circuit 10 and directing circuit 142 for sterilization of the hemodialysis system. In some embodiments, one or more of these circuits (e.g., blood flow circuit, balancing circuit, directing circuit, and / or mixing circuit) include cassettes containing the necessary valves and pumps to control flow through the sections. Examples of such systems are described in more detail below.

[0094] FIG. 2B is a schematic diagram of a hemodialysis system according to an embodiment of the present invention. In this diagram, a blood flow cassette 22 is used to control flow through the blood flow circuit 10, and a dialysate cassette 21 is used to control flow through the dialysate circuit. The blood flow cassette includes at least one inlet valve 24 (although alternatively includes one or more inlet valves) to control the flow of blood through the cassette 22. Additionally, an anticoagulant valve or pump 12 controls the flow of anticoagulant into the blood, and in an embodiment, the blood flow pump 13 comprises a pair of pod pumps. These pod pumps may be of the type disclosed in U.S. patent application Ser. No. 60 / 792,073, filed Aug. 14, 2006, and entitled "Extracorporeal Thermal Therapy System and Method," or U.S. patent application Ser. No. 11 / 787,212, filed Aug. 13, 2007, and entitled "Fluid Pumping System, Apparatus, and Method" (or variations thereof). All pumps and valves in this example system can be controlled by a control system, such as an electronic digital control system, although other control systems are possible in alternative embodiments.

[0095] Providing two pod pumps allows blood to flow continuously through the blood flow circuit 10, although a single pod pump could alternatively be used. The pod pump includes dynamic inlet and outlet valves (instead of static check valves at the inlet and outlet) that allow flow in the blood flow circuit 10 to be reversed under certain circumstances. For example, by reversing the flow in the blood flow circuit, the hemodialysis system can verify that the outlet of the blood flow circuit is properly connected to the patient and that treated blood is being properly returned to the patient. For example, if the patient connection becomes disconnected, such as by being dropped, reversing the blood flow pump will draw in air rather than blood. This air is detected by a standard air detector built into the system.

[0096] In another embodiment, the blood outlet valve 26 and air trap or filter 19, located downstream of the dialysis machine, are incorporated within the blood flow cassette 22. The pod pump and all valves within the blood flow cassette 22 (including the valves associated with the pod pump inlet and outlet) are pneumatically actuated. In one embodiment, the source of positive and negative gas pressure is provided by the base unit or other device that holds the cassette. However, in another embodiment, the source of positive and negative gas pressure may be provided by an external device fluidly coupled to the cassette or by a device incorporated within the system. The pump chamber is actuated as disclosed in the aforementioned U.S. patent application Ser. No. 60 / 792,073, filed Aug. 14, 2006, and entitled "Extracorporeal Thermal Therapy System and Method," and U.S. patent application Ser. No. 11 / 787,212, filed Aug. 13, 2007, and entitled "Fluid Pumping System, Device, and Method." For example, the pump may be controlled and end-of-stroke detected as described below. The blood flow cassette 22 further includes an integrally formed spike for receiving a vial of anticoagulant.

[0097] In one embodiment, the anticoagulant pump includes three fluid valves (controlled by a control fluid) and one pump compartment (although in other embodiments, more than one pump compartment is provided). The valves connect the compartments to a filtered vent, to an anticoagulant vial (or other anticoagulant supply, such as a bag or vial), or to the blood flow path. The anticoagulant pump can be powered by sequentially opening and closing the fluid valves, e.g., by controlling the pressure in the pump compartment with the control fluid. As anticoagulant is removed from the vial, it is replaced by an equal volume of air, e.g., to maintain a relatively constant pressure within the vial. Substituting air for anticoagulant as described above is accomplished, for example, by (i) opening a valve from a filtered vent to the pump compartment, (ii) forcing air into the compartment by connecting a negative pressure source to the chamber, (iii) closing the vent valve, (iv) opening a valve connecting the compartment to the vial, and (v) forcing air into the vial by connecting a positive pressure source to the compartment. Anticoagulant is pumped from the vial into the blood flow path by a similar sequence, using valves on the vial and blood flow path rather than the valves on the vent and vial.

[0098] Figure 3A is a schematic diagram illustrating an embodiment of the embodiment shown in Figure 2A. Figure 3A details how blood flow circuit 141, balancing circuit 143, directing circuit 142, and mixing circuit 25 are provided in a cassette, interrelated, and associated with dialyzer 14, ultrafilter 73, and / or heater 72 in an embodiment of the present invention. While Figure 3A illustrates only one possible hemodialysis system for the embodiment of Figure 2A, other fluid circuits, modules, flow paths, layouts, etc. are possible in alternative embodiments. Examples of such systems are described in more detail below. Further, these include U.S. patent application Ser. No. 60 / 903,582, filed February 27, 2007, entitled "Hemodialysis System and Method," U.S. patent application Ser. No. 60 / 904,024, filed February 27, 2007, entitled "Hemodialysis System and Method," U.S. patent application Ser. No. 11 / 871,680, filed October 12, 2007, entitled "Pump Cassette ... No. 11 / 871,712, filed October 12, 2007, entitled "Pump Cassette," U.S. patent application Ser. No. 11 / 871,787, filed October 12, 2007, entitled "Pump Cassette," U.S. patent application Ser. No. 11 / 871,793, filed October 12, 2007, entitled "Pump Cassette," or U.S. patent application Ser. No. 11 / 871,803, filed October 12, 2007, entitled "Cassette System Integrated Apparatus," each of which is incorporated herein by reference in its entirety.

[0099] The elements shown in FIG. 3A are described below. Briefly, blood flow circuit 141 includes anticoagulant supply 11 and blood flow pump 13, which pumps blood from the patient to dialyzer 14. While anticoagulant supply 11 is shown positioned within the blood flow path to the dialyzer, it may alternatively be located within the blood flow path to the patient or in another suitable location. Anticoagulant supply 11 is located downstream of blood flow pump 13. Balancing circuit 143 includes two pumps: dialysate pump 15, which pumps dialysate to dialyzer 14, and bypass pump 35. Directing circuit 142 includes dialysate pump 159, which pumps dialysate from dialysate tank 169 through heater 72 and / or ultrafilter 73 and into the balancing circuit. Directing circuit 142 pumps waste from balancing circuit 143 to drain 31. In some embodiments, blood flow circuit 141 is connected to directing circuit 142 via conduit 67, e.g., for sterilization, as described below. Dialysate flows from the dialysate supply to the dialysate tank 169 .

[0100] In embodiments, the present invention provides a method for producing dialysate from water contained within or supplied to the system and at least one supply of solutes contained within or supplied to the system. For example, as shown in Figures 3A, 3B, 7A, and 7B, dialysate is produced in mixing circuit 25. Water from water supply 30 flows through directing circuit 142 and enters mixing circuit 25. Dialysate ingredients 49 (e.g., bicarbonate and acid) are also added to mixing circuit 25, and a series of mixing pumps 180, 183, and 184 are used to produce dialysate, which is then sent to directing circuit 142. This method and its control to ensure acceptable dialysate quality is produced and maintained throughout treatment are described in more detail below.

[0101] One of the fluid circuits in this example system is the blood flow circuit, i.e., blood flow circuit 141 shown in FIG. 3A. In the blood flow circuit, blood from the patient is pumped through the dialyzer and returned to the patient. As will be described below, in some embodiments, the blood flow circuit is located in a cassette, but this need not be the case. In some embodiments, the flow of blood through the blood flow circuit is balanced with the flow of dialysate through the dialysate flow path, particularly through the dialyzer and balancing circuit.

[0102] FIG. 4A shows an example of a blood flow circuit. Typically, blood flows from the patient through arterial line 203, via blood pump 13, to dialyzer 14 (the flow direction during normal dialysis is indicated by arrow 205; however, in other modes of operation, flow is in another direction). Optionally, anticoagulant is introduced into the blood from an anticoagulant supply via anticoagulant pump 80. As shown in FIG. 4A, the anticoagulant enters the blood flow path after the blood has passed through blood pump 13. However, in other embodiments, the anticoagulant is added at a suitable location along the blood flow path. In other embodiments, anticoagulant supply 11 is located downstream of the blood pump. After passing through dialyzer 14 and undergoing dialysis, the blood returns to the patient through venous line 204, optionally via an air trap or blood sample port 19.

[0103] As shown in FIG. 4A, the blood flow cassette 141 further includes one or more blood flow pumps 13 to move blood through the blood flow cassette. The pumps may be, for example, pumps driven by a control fluid, as described below. In one embodiment, for example, the pumps 13 comprise two (or more) pod pumps, i.e., pod pumps 23 shown in FIG. 4A. In this embodiment, each pod pump includes a rigid chamber with a flexible diaphragm or membrane separating the chamber into a fluid compartment and a control compartment. These compartments are provided with four inlet or outlet valves: two in the fluid compartments and two in the control compartment. The valves in the chamber's control compartment are bidirectional proportional valves, one connected to a first source of control fluid (e.g., a high-pressure air source) and the other connected to a second source of control fluid (e.g., a low-pressure air source) or a vacuum sink. The fluid valves in the compartments are openable and closable to allow fluid flow when the pod pump is operating. Examples of these pod pumps are disclosed, but are not limited to, in U.S. patent application Ser. No. 60 / 792,073, filed Aug. 14, 2006, and entitled "Extracorporeal Thermal Therapy System and Method," and U.S. patent application Ser. No. 11 / 787,212, filed Aug. 13, 2007, and entitled "Fluid Pumping System, Apparatus, and Method," both of which are incorporated herein by reference in their entireties. Further details of pod pumps are provided below. When more than one pod pump is provided, the pod pumps can be operated in any suitable manner, for example, synchronously or asynchronously, in phase or out of phase.

[0104] In this embodiment, for example, the two pumps may be rotated out of phase to affect the pumping period, i.e., one pump chamber is filled and the second pump chamber is emptied. The phase relationship between 0° (pod pumps drive in the same direction) and 180° (pod pumps drive in opposite directions) can be selected to obtain the desired pumping period.

[0105] A 180° phase relationship results in continuous flow into and out of the pod pump. For example, this is preferable when continuous flow is required, such as with a dual-needle flow or a "Y" or "T" junction. However, a 0° phase relationship can be useful in single-needle flow, or in other embodiments. In a 0° phase relationship, the pod pump fills first through the needle, and the same needle is used to return blood to the patient through the blood flow path. Additionally, in some embodiments, actuation between 0° and 180° can be used to achieve a push-pull relationship across the dialysis machine (hemodiafiltration or continuous backflow). Figures 8A-8C show 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 volume of both pod pumps are plotted against the time axis. These times and fluid rates are arbitrarily selected and are shown to illustrate the relationship between the pod pumps at different phases. For example, at a 180° phase relationship, as shown in Figure 8B, the total volume remains approximately constant.

[0106] In one embodiment, as shown in FIG. 4, an anticoagulant (e.g., heparin or other anticoagulant known to those skilled in the art) is mixed with the blood in blood flow cassette 141. For example, the anticoagulant may be contained in vial 11 (or other anticoagulant supply, such as tubing or a bag), and blood flow cassette 141 may receive the anticoagulant vial with an integrally formed spike 201 (which in one embodiment is a needle) capable of piercing the vial's seal. The spike may be formed from plastic, stainless steel, or other suitable material, and in one embodiment, may be a sterilizable material. For example, the material may be sufficiently resistant to high temperatures and radiation to sterilize the material. For example, as shown in FIG. 4, spike 201 may be integrally formed with blood flow cassette 141, vial 11 may be positioned on the spike, and the spike may pierce the vial's seal. This allows the anticoagulant to mix with the blood in the blood flow path and flow into the blood flow cassette to potentially be mixed with dialysate, as described below.

[0107] In some embodiments, a third pump 80 of the blood flow cassette 141, functioning as a metering chamber, can be used to control the flow of anticoagulant into the blood within the cassette. The third pump 80 may be the same design as pump 13 or a different design. For example, the third pump 80 may be a pod pump and / or may be driven by a control fluid, such as air. For example, as shown in FIG. 4, the third pump 80 includes a rigid chamber with a flexible diaphragm separating the chamber into a fluid compartment and a control compartment. A valve in the control compartment of the chamber is connected to a first control fluid source (e.g., a high-pressure air source), while the other compartment is connected to a second control fluid source (e.g., a low-pressure air source) or a vacuum sink. The valve in the fluid compartment of the chamber opens or closes in response to the control compartment, thereby controlling the flow of anticoagulant into the blood. Further details of the pod pump are provided below. As described below in some embodiments, air is introduced into the blood flow path through a filter 81.

[0108] Fluid management system (FMS) measurements are used to measure the volume of fluid pumped through the pump chamber during a membrane stroke or to detect air in the pump chamber. Fluid management system methods are described in U.S. Patent Nos. 4,808,161, 4,826,482, 4,976,162, 5,088,515, and 5,350,357, each of which is incorporated by reference in its entirety. In some examples, the volume of fluid delivered by an anticoagulant pump, dialysate pump, or other membrane-based pump is determined using a fluid management system algorithm that uses chamber pressure changes to calculate volume measurements at the end of the fill stroke and the end of the deliver stroke. The difference between the calculated volumes at the end of the fill stroke and the end of the deliver stroke is the actual stroke volume. This actual stroke volume can be compared to the expected stroke volume for a given chamber size. If the actual volume and the expected volume differ significantly, the stroke is not properly completed and an error message is generated.

[0109] As stroke volume is collected by the scale, calculations are performed in the background to determine a calibration value for the reference chamber. The FMS system vents to atmosphere for the FMS system measurements. Alternatively, the system may vent to a high-pressure positive source and a low-pressure negative source for the FMS system measurements. This provides the following benefits: (1) If the high-pressure source is a pressure tank with a controlled pressure, there is an opportunity to cross-check the tank and chamber pressure sensors to ensure they are the same when the chamber is open to the tank. This can be used to detect pressure sensor failures or valve failures. (2) Using higher or lower pressures for venting can produce a larger pressure difference for the FMS system measurements, resulting in a better answer.

[0110] In some embodiments, the blood flow circuit 141 includes an air trap 19 incorporated into the blood flow circuit 141. The air trap 19 is used to remove air bubbles within the blood flow path. In some embodiments, the air trap 19 can separate air from the blood due to gravity. In some embodiments, the air trap 19 further includes a port for blood sampling. Air traps are well known to those skilled in the art.

[0111] According to another aspect of the present invention, an air trap 19 is provided in the blood flow path after blood exits the dialyzer and before returning to the patient. As shown in Figures 4C and 4D, the air trap 19 has a spherical or spheroidal container 6 with an inlet port 7 near the top of the container, offset from its vertical axis, and an outlet port 9 at the bottom. The curved shape of the trap's inner wall 4 guides the blood along the wall as it descends to the bottom of the container under the force of gravity, helping to remove air bubbles from the blood. Air present in the blood exiting the dialyzer 14 through the outlet 9 enters the top of the air trap 19 and remains there as the blood exits the bottom outlet and enters the venous blood line 204. By providing the inlet port 7 near the top of the trap 19, it is also possible to circulate blood through a trap with little or no air in the container (known as a "run-full" air trap). Eliminating the air-blood interface for normal blood circulation within the trap is advantageous. Providing inlet port 7 at or near the top of the vessel also allows most or all of the air present in the trap to be removed from the trap by reversing the flow of fluid through the blood line (i.e., from the bottom to the top of trap 19, venting through the inlet port of trap 19). In some embodiments, a self-sealing port 3, such as a self-sealing stopper with a dividing septum or membrane, or another configuration, is provided at the top of the trap, allowing air to be vented from the vessel (e.g., via a syringe). The blood-facing surface of the self-sealing membrane can be positioned approximately flush with the top of the trap interior to facilitate cleaning of the self-sealing port during disinfection. The self-sealing port 3 can also serve as a blood sample extraction site and / or for introducing fluids, drugs, or other compounds into the blood circuit. If needle access is anticipated, a sealed rubber-type stopper can be used. Using a self-sealing stopper with a dividing septum allows for sample extraction and fluid transfer using a needleless system.

[0112] Additional fluid connections 82 also connect blood flow circuit 10 to a patient and / or to a fluid source for priming or sterilizing the system including blood flow circuit 10. Typically, during sterilization, arterial line 203 and venous line 204 are directly connected to directing circuit 142 via conduit 67, which allows the sterilizing fluid (e.g., hot water or a combination of hot water and one or more chemicals, in some embodiments) to be returned to directing circuit 142 for recirculation through dialysis machine 14 and blood flow circuit 141. This sterilization is similar to that disclosed in U.S. Patent No. 5,651,898 to Kenley et al., which is incorporated herein by reference in its entirety, and which is further described below.

[0113] The pressure in the arterial line 203 is maintained at a subatmospheric pressure in an embodiment to pump blood from the patient. When a pod pump is used, the pressure in the blood flow pump 13 is inherently limited to the pressure available from the positive and negative pressure tanks used to power the pump. In the event of a pressure tank or valve failure, the pressure in the pump chamber approaches the tank pressure. This causes fluid pressure to rise to match the tank pressure up to the diaphragm in the "bottom" of the pod pump (i.e., it is immobile because it is in contact with a surface). The fluid pressure does not exceed safe limits and balances with natural body fluid pressure. This failure naturally stops the pod pump from operating without any intervention.

[0114] Non-limiting examples of blood flow cassettes are shown in Figures 30-33. Figures 30A and 30B show the exterior of an example cassette top plate 900. Top plate 900 contains one half of pod pumps 820, 828. This half is the fluid half through which the source fluid flows. Two fluid paths 818, 812 are shown. These paths lead to the respective pod pumps 820, 828.

[0115] The pod pumps 820, 828 include elevated flow paths 908, 910. The elevated flow paths 908, 910 allow fluid to continue flowing through the pod pumps 820, 828 after a diaphragm (not shown) reaches the end of a stroke. Thus, the elevated flow paths 908, 910 minimize diaphragms that could trap air or fluid in the pod pumps 820, 828 or block the inlets or outlets of the pod pumps 820, 828, preventing continuous flow. The elevated flow paths 908, 910 have predetermined dimensions in one embodiment, and in some embodiments, the dimensions are comparable to the dimensions of the fluid paths 818, 812. However, in other embodiments, the elevated flow paths 908, 910 are narrower, and in still other embodiments, the elevated flow paths 908, 910 can be any size, as the purpose is to control the fluid to achieve a desired flow rate or volume of the fluid. In some embodiments, the raised channels 908, 910 and fluid paths 818, 812 may be different sizes. Therefore, the dimensions provided herein for the raised channels, pod pumps, valves, and other aspects are exemplary and illustrative only. Other embodiments are apparent.

[0116] In one embodiment of this cassette, the top plate includes a spike 902 as well as a vessel pedestal 904. The spike 902 is empty in this example and is fluidly connected to the fluid path. In some embodiments, a needle is attached to the spike. In another embodiment, the needle is connected to a vessel attachment.

[0117] 30C and 30D show the interior of the top plate 900. Fried channels 908, 910 connect to inlet channels 912, 916 and outlet channels 914, 918 of the pod pumps 820, 828. The fried channels are described in detail above.

[0118] The metering pump (not shown) includes a connection to the spike airway 902 as well as a connection to the vent 906. In one embodiment, the vent 906 includes an air filter (not shown). The air filter is, in some embodiments, a particulate air filter. In some embodiments, the filter is a somicron hydrophobic air filter. In various embodiments, the size of the filter varies and depends on the desired results. The metering pump is powered by taking in air through the vent 906, pumping it through the spike airway 902 into a container of a second fluid (not shown), and then pumping a volume of the second fluid from the container (not shown) through the spike airway 902 and into the fluid line at point 826. This fluid path for the metering pump is indicated by the arrows in FIG. 30C.

[0119] Figures 31A and 31B show the fluid side of the midplate 1000. Complementary areas of the internal top plate flow channels are shown. These areas are slightly raised to indicate the conductive surface finish provided by laser welding, one mode of fabrication in this embodiment. Other modes of fabrication of the cassette are described above. Fluid inlet 810 and fluid outlet 824 are also shown in this view.

[0120] Figures 31C and 31D show the air side of midplate 1000 in one embodiment. As shown in Figure 31A, the air side of valve holes 808, 814, 816, and 822 correspond to the holes on the fluid side of the midplate. As shown in Figures 33C and 33D, diaphragms 1220 complete valves 808, 814, 816, and 822, and diaphragms 1226 complete pod pumps 820 and 828. Metering pump 830 is completed by diaphragm 1224. Valves 808, 814, 816, 822, 832, 834, and 836 are air actuated. The diaphragms are pulled away from the holes, drawing in liquid. When the diaphragms are pressed toward the holes, liquid is forced through. Fluid flow is directed by opening and closing valves 808, 814, 816, 822, 832, 834, 836.

[0121] 31A and 31C show that the metering pump includes three holes 1002, 1004, and 1006. Hole 1002 draws air into the metering pump. A second hole 1004 pushes and moves air into the spike or source container, which also draws liquid from the source container. A third hole 1006 pushes and moves a second fluid from metering pump 830 to point 826 in the fluid line.

[0122] Valves 832, 834, and 836 drive a second fluid metering pump. Valve 832 is a second fluid or spike valve. Valve 834 is an air valve, and valve 836 is a valve that controls fluid flow to region 826 of the fluid line.

[0123] Figures 32A and 32B show the inside of bottom plate 1100. The inside of pod pumps 820, 828, metering pump 830, and the drive or air chambers for valves 808, 814, 816, 822, 832, 834, and 836 are shown. Pod pumps 820, 828, metering pump 830, and valves 808, 814, 816, 822, 832, 834, and 836 are driven by an air source. Figures 32C and 32D show the outside of bottom plate 1100. The air source is attached to this side of the cassette. In one embodiment, tubing connects the valves and the surface of pump 1102. In some embodiments, the valves are ganged, with more than one valve driven by the same air line.

[0124] Figures 33A and 33B show an assembled cassette 1200 with a second fluid container (or other source) 1202. The container 1202 contains the second fluid source and is attached to a spike (not shown) by a container attachment 1206. The spike is attached within the container attachment 1206 and faces upward so as to penetrate the top of the container 1202. The container 1202 is held on the opposite side from the container attachment 1206. The spike is in fluid communication with the liquid channel, similar to the recessed air passage shown in Figures 30C and 30D. As shown, an air filter 1204 is attached to a vent (not shown, shown in Figure 30A as 906). Although not shown in Figure 33A, a container pedestal (shown in Figure 30A as 904) is located below the container attachment 1206.

[0125] In some examples, the metering pump is a fluid management system pump that, in conjunction with a reference chamber, can be monitored with a pressure transducer to determine the volume of fluid delivered. The fluid management system algorithm uses the change in pressure to calculate volume measurements at the end of the fill stroke and the end of the deliver stroke. The difference in the calculated volumes at the end of the fill stroke and the end of the deliver stroke is the actual stroke volume. This actual stroke volume can be compared to the expected stroke volume for a given size chamber. If the actual volume differs significantly from the expected volume, the stroke is not properly completed and an error message is generated. The fluid management system is vented to atmosphere for fluid management system calibration. Alternatively, the system may be vented to a high-pressure positive source and a low-pressure negative source for fluid management system calibration. In some embodiments, the metering pump (e.g., an anticoagulant pump) is primed. Priming the pump removes air from the metering pump and fluid path and ensures that the pressure within the fluid container (e.g., an anticoagulant vial) is acceptable.

[0126] The metering pump can be designed so that air in the pump chamber flows into the vial. The test involves closing all of the metering pump's fluid valves to measure the outside volume, applying a vacuum to the pump's fluid management system chamber, opening the valves to introduce fluid from the vial into the pump chamber, then measuring the outside volume (again), applying pressure to the fluid management system chamber, opening the valves to force the fluid back into the vial, then measuring the outside volume (again). The change in outside volume caused by fluid flow should correspond to the known volume of the pump chamber. If the pump chamber cannot be filled from the vial, the vial pressure is too low and air must be pumped in. Conversely, if the entire contents of the pump chamber cannot be transferred to the vial, the vial pressure is too high and some of the anticoagulant must be pumped out of the vial. The anticoagulant pumped from the vial during the test can be discarded, for example, via a drain.

[0127] During normal delivery of heparin or other medication to the blood line, the pressure within the vial can be measured periodically. When the vial pressure approaches a predetermined threshold, e.g., below atmospheric pressure, the metering pump can first introduce air into the vial via the metering pump vent, helping to restore normal vial pressure and ensure a reasonably accurate amount of medication is expelled from the vial. When the vial pressure approaches a predetermined threshold above atmospheric pressure, the metering pump can refrain from blowing any more air into the vial before next expelling medication from the vial.

[0128] Figures 33C and 33D are exploded views of the assembled cassette 1200 shown in Figures 33A and 33B, respectively. In these figures, an embodiment of the pod pump diaphragm 1226 is shown. The diaphragm gasket provides a seal between the liquid chamber (in the top plate 900) and the air or actuation chamber (in the bottom plate 1100). The dimpled texture of the diaphragm 1226 dome provides additional space for air and fluid to escape the chamber, especially at the end of the stroke.

[0129] The system of the present invention further includes a balancing circuit, such as balancing circuit 143 shown in FIG. 3A. In some embodiments, a blood flow circuit is provided in the cassette, even if not required. Within the balancing circuit, the flow of dialysate into and out of the dialyzer is balanced so that equal volumes of dialysate enter and exit the dialyzer (although this balance may be altered in certain cases by the use of a bypass pump, as described below). Additionally, in some embodiments, the flow of dialysate is balanced by the dialyzer so that the pressure of the dialysate within the dialyzer is equal to the pressure of the blood passing through the blood flow circuit.

[0130] Additionally, in some instances, the dialysate flow is balanced by the dialyzer so that the dialysate pressure within the dialyzer is approximately equal to the pressure of the blood passing through the blood circuit. In some instances, the flow of blood through the blood flow circuit 141 and the dialyzer is synchronized with the flow of dialysate in the dialysate flow path through the dialyzer. Because fluid may pass through the semipermeable membrane of the dialyzer, and because the balancing circuit pump operates at positive pressure, the balancing circuit pump can use pressure and control data from the blood flow pump to time the delivery stroke to the dialyzer to synchronize with the delivery stroke of the blood pump.

[0131] A non-limiting example of a balancing circuit is shown in Figure 5. In the balancing circuit 143, dialysate flows from an optional ultrafiltration membrane 73 to one or more dialysate pumps 15 (two as shown in Figure 5). The dialysate pump 15 in this figure includes two pod pumps 161, 162, two balancing chambers 341, 342, and a pump 35 for bypassing the balancing chambers. The balancing chambers are formed from a rigid chamber with a flexible diaphragm that separates the chamber into two separate fluid compartments, configured so that fluid entry into one compartment expels fluid from the other compartment, and vice versa. Examples of pumps that can be used as pod pumps or balance chambers are disclosed, but are not limited to, U.S. patent application Ser. No. 60 / 792,073, filed April 14, 2006, and entitled "Extracorporeal Thermal Therapy System and Method," or U.S. patent application Ser. No. 11 / 787,212, filed April 13, 2007, and entitled "Fluid Pumping System, Apparatus, and Method," both of which are incorporated herein by reference in their entireties. Additional examples of pod pumps are described in more detail below. As shown in FIG. 5, multiple valves may be "ganged," or synchronized in pairs, so that all valves in a pair open and close simultaneously.

[0132] More specifically, in one embodiment, flow balancing works as follows. Figure 5 shows that in a first synchronized and controlled set of valves 211, 212, 213, 241, 242, valves 211, 212, 213 are ganged and valves 241 and 242 are ganged; similarly, in a second synchronized and controlled set of valves 221, 222, 223, 231, 232, valves 221, 222, 223 are ganged and valves 231 and 232 are ganged. At a first point in time, the first ganged set of valves 211, 212, 213, 241, 242 are open, and the second ganged set of valves 221, 222, 223, 231, 232 are closed. Fresh dialysate flows into balancing chamber 341, and used dialysate flows from dialyzer 14 to pod pump 161. Fresh dialysate does not flow into balancing chamber 342 because valve 221 is closed. As fresh dialysate flows into balancing chamber 341, the spent dialysate in balancing chamber 341 is forced out and out of balancing circuit 143 (the spent dialysate cannot enter pod pump 161 because valve 223 is closed). At the same time, pod pump 162 forces the dialysate in the pod pump into balancing chamber 342 (through open valve 213; valves 242 and 222 are closed, ensuring the spent dialysate flows into balancing chamber 342). This forces the fresh dialysate contained in balancing chamber 342 out of balancing circuit 143 and into dialyzer 14. Additionally, pod pump 161 draws spent dialysate from dialyzer 14 into pod pump 161. This is further shown in FIG. 18A.

[0133] Once pod pump 161 and balancing chamber 341 are filled with dialysate, a first set of valves 211, 212, 213, 241, and 242 close, while a second set of valves 221, 222, 223, 231, and 232 open. Fresh dialysate flows into balancing chamber 342 instead of balancing chamber 341 because valve 212 is closed and valve 221 is open. As fresh dialysate flows into balancing chamber 342, the spent dialysate therein is forced out of the balancing circuit because valve 213 is closed. Because valve 232 is closed and valve 222 is open, the spent dialysate is prevented from flowing to pod pump 161. The fresh dialysate contained in balancing chamber 341 is thus directed into the dialyzer (because valve 241 is open and valve 212 is closed). At the end of this process, pod pump 162 and balancing chamber 342 are filled with dialysate. This returns the state of the system to that at the beginning of this specification and the cycle repeats, ensuring a constant flow of dialysate to and from the dialyzer, as further shown in Figure 18B.

[0134] A specific example is when a vacuum (e.g., 4 psi (approximately 27.586 kPa) vacuum) is applied to a first ganged set of valves and a positive pressure (e.g., 20 psi (approximately 137.931 kPa) (1 psi is 6.89475 kPa) air pressure) is applied to a second ganged set of valves, causing them to close (or vice versa). Each pod pump pumps dialysate into one of the volumes of one of the balance chambers 341, 342. By forcing dialysate into a volume of the balance chamber, an equal amount of dialysate is squeezed out of the other volume in the balance chamber by a septum. In each balance chamber, one volume is occupied by fresh dialysate toward the dialyzer, and the other volume is occupied by used dialysate from the dialyzer. Thus, the volumes of dialysate entering and leaving the dialyzer are kept approximately equal.

[0135] It should be noted that any valve associated with a balance chamber can be opened and closed at any suitable pressure. However, it may be advantageous to apply a lower or more controlled pressure than the pressure that ultimately holds the valve closed (the "holding pressure") from the time the valve first begins to close until it fully closes. Applying a pressure equal to the holding pressure to cause the valve to close may cause a transient pressure rise in the fluid line sufficient to cause leakage in downstream valves that are already closed, adversely affecting the balance of dialysate flow into and out of the dialyzer. Closing the inlet and / or outlet valves of the dialysate pump and balance chamber at a lower or more controlled pressure can improve the balance of dialysate flow into and out of the dialyzer. In embodiments, this can be achieved, for example, by employing pulse width modulation ("PWM") to apply pressure to the valve's fluid control lines. Without being limited by the following theory, it may be advantageous to use a moderate or controlled pressure for a "slow-closing" valve, for example, for the following reasons: (1) In some instances, the pressure in the balance chamber may transiently exceed the holding pressure of the closed balance chamber outlet valve (e.g., caused by applying excessive pressure to close the balance chamber inlet valve against the mass of fluid behind the valve septum). The transient pressure increase in the fluid line may overcome the holding pressure of the closed outlet valve, causing fluid leakage between the two sides of the balance chamber and creating an imbalance in fluid delivery. (2) Furthermore, the presence of air or gas between the balance chamber and the balance chamber valve, combined with rapid valve closure, may cause excess fluid to be forced into the balance chamber without being balanced by fluid from the other side of the balance chamber.

[0136] When the septum approaches the walls of the balancing chambers (causing one volume of the balancing chamber to approach its minimum and the other volume to approach its maximum), positive pressure is applied to the first interlocking set of valves, causing them to close. Vacuum is applied to the second interlocking set of valves, causing them to open. The pod pump sends dialysate to one of the other volumes of the balancing chambers 341, 342. Again, an equal amount of dialysate is squeezed from the other volume of the balancing chamber by the septum, forcing dialysate into the volume of the balancing chamber. In each balancing chamber, one volume is occupied by fresh dialysate going to the dialyzer, and the other volume is occupied by used dialysate from the dialyzer. Thus, the volumes of dialysate going into and out of the dialyzer are maintained equal.

[0137] FIG. 5 also illustrates a bypass pump 35 capable of directing dialysate flow from the dialyzer 14 through the balance circuit 143 without passing through both pod pumps 161 and 162. In this illustration, bypass pump 35 is a pod pump similar to those described above, with a rigid chamber and a flexible diaphragm separating each chamber into a fluid compartment and a control compartment. This pump may be the same as or different from the other pod pumps and balance chambers described above. For example, this pump may be a pump such as those described in U.S. patent application Ser. No. 60 / 792,073, filed April 14, 2006, and entitled "Extracorporeal Thermotherapy System and Method," or U.S. patent application Ser. No. 11 / 787,212, filed April 13, 2007, and entitled "Fluid Pumping System, Apparatus, and Method," each of which is incorporated herein in its entirety. Pod pumps are described in more detail below.

[0138] When a control fluid is used to drive this pump, dialysate is pumped through the dialyzer without balancing the blood flow through the dialyzer. This causes fluid flow from the patient through the dialyzer to drain. The bypass is useful, for example, to reduce the amount of fluid a patient has, which typically builds up due to the patient's inability to lose fluid (primarily water) through the kidneys. As shown in Figure 5, the bypass pump 35 is controlled by a control fluid (e.g., air) independently of the drive of the pod pumps 161 and 162. This configuration allows for easy control of fluid removal from the patient without driving the balancing pumps to drain the fluid from the patient.

[0139] To obtain balanced flow across the dialyzer, the blood flow pump, the pumps in the balancing circuit, and the pumps in the directing circuit (described below) are driven in coordination to ensure that the flow into the dialyzer is equal to the flow normally out of the dialyzer. When ultrafiltration is required, the ultrafiltration pump (if there is one) is driven independently of some or all of the other blood and dialysate pumps to obtain the desired ultrafiltration rate.

[0140] To prevent dialysate outgassing, the balancing circuit pump is always held at a pressure greater than atmospheric pressure. In contrast, however, the blood flow pump and directing circuit pump use a pressure less than atmospheric pressure to pull the diaphragm toward the chamber wall for the fill stroke. Because fluid is potentially moving across the dialyzer and the balancing circuit pump is operating at a positive pressure, the balancing circuit pump can use information from the blood flow pump to operate in a balanced flow mode.

[0141] In one embodiment, when operating in the balanced mode, in the absence of pumping pressure from the blood pump, the balance circuit pump diaphragm pushes fluid across the dialyzer, preventing the balance circuit pod from filling completely. Therefore, the blood pump dynamically reports when there is a stroke. The balance pump activates when the blood pump is stroking. When the blood pump is not pumping blood, the valves controlling flow from the dialyzer to the balance pump (and the other balance valves associated with these valves, as described above) are closed, preventing fluid from moving from the blood side to the dialysate side. When the blood pump is not pumping, the balance pump effectively freezes, and stroking continues when the blood pump begins pumping again. The balance pump fill pressure is set to a minimum positive value to ensure the pump drives above atmospheric pressure with minimal impedance. Additionally, the balance pump delivery pressure is set to the blood flow pump pressure to normally match the pressure on both sides of the dialyzer, minimizing flow across the dialyzer on the inner pump stroke.

[0142] In some instances, it may be advantageous to have the dialysate pump deliver dialysate to the dialyzer at a pressure higher than the delivery pressure of the blood pump. This helps, for example, to ensure that clean dialysate is delivered to the dialyzer. In some instances, the delivery pressure on the dialysate pump is set high enough to force the internal pump to complete its stroke, but not so high that it stops blood flow through the dialyzer. Conversely, in some instances, when the dialysate pump is receiving used dialysate from the dialyzer, it may be advantageous to set the pressure within the dialysate pump lower than the outlet pressure on the blood side of the dialyzer. This helps to ensure that the receiving dialysate chamber can always be filled, and therefore that enough dialysate is available to complete a full stroke in the balance chamber. Flows across semipermeable membranes caused by such pressure differences tend to cancel each other out; otherwise, the pump algorithm attempts to match the average pressures on the dialysate and blood sides of the dialyzer.

[0143] Convection across the dialyzer membranes may be beneficial because the constant, repetitive shifting of fluid in and out of the dialyzer, while not resulting in net ultrafiltration, still helps prevent clot formation within the blood tubing and dialyzer. This, in turn, may allow for lower heparin dosages, extending the useful life of the dialyzer and facilitating cleaning and reuse of the dialyzer. Backflushing has the added benefit of further promoting solute removal by convection. In another example, a type of continuous backflushing across the dialyzer membranes can also be achieved by slightly adjusting the synchronization of the blood transport stroke and the dialysate transport stroke through the dialyzer.

[0144] In some embodiments, the pod pump 15 (FIG. 89) of the internal dialysate cassette 143 may be phased to minimize blockages on the blood side of the dialyzer 14. The internal dialysate pop pump 15 may be phased in conjunction with the blood pump 13 to alternately pump fluid to the blood side of the dialyzer 14 and back to the dialysate side with each stroke of the internal dialysate pump 15. The timing of the pump strokes, valve opening, valve closing, and pop pump drive pressure may be controlled by the automation computer 6106, which may control the pumps and valves and receive pressure data via the pneumatic distribution module 9000. Phasing the internal dialysate pump to push fluid back and forth across the dialyzer membrane has the benefit of, but not limited to, better removal of large solutes from the blood and minimal blockages on the dialyzer.

[0145] Flow within the dialyzer 14 can be controlled by pumps and valves, as shown schematically in FIG. 89. An example of the timing and function of the blood and dialysate pumps is plotted in FIG. 12K. The blood pump pod pumps 23a, 23b can operate 180 degrees out of phase to provide a nearly continuous flow of blood to the dialyzer 14. Cleaned blood and some dialysate fluid can flow from the dialyzer to the venous line 204 in the blood tubing set. Fresh dialysate can flow from the balancing pod 342 into the dialyzer, while spent dialysate and fluid from the blood side flow into the receiving pod pump 161. The other dialysate pump 162 forces spent dialysate into the balancing pod 342, allowing clean dialysate to flow from the balancing pod 342. The spent dialysate and clean dialysate are separated by a septum. The other balancing pod 341 may be filled with fresh dialysate from the external dialysate pump 159 in preparation for the next pump stroke.

[0146] Blood pump 23A may be caused to deliver blood to dialyzer 14 by opening the downstream valve, closing the upstream valve, and increasing the pod pressure measured by 193. Blood pump 23b may be caused to fill from the arterial line by opening the upstream valve, closing the downstream line, and reducing the pressure below atmospheric pressure measured by 197.

[0147] At time 12411, an exemplary sequence can be initiated for pushing and pulling fluid across the dialyzer membrane, with blood pump 23A delivering blood to the dialyzer and blood pump 23b filling. Measured pressures for the deliver and fill pumps are plotted at 12420 and 12430, respectively. Pressures 12420, 12430 can vary periodically in response to variable valves 198, 199 sinusoidally varying the valve port sizes. Automation computer 6106 can monitor pressure readings 12420 and 12430 to detect end-of-stroke in the blood pumps.

[0148] The internal dialysate pumps and valves may be controlled between times 12411 and 12412 to allow fluid from the blood in the dialyzer 14 to flow into the receiving dialysate pump pod 161. Valve 231 may be closed to prevent clean dialysate from flowing into the dialyzer 14. Valve 232 may be open and pump pod pressure 12440 may be low to allow fluid from the blood to flow into the dialysate pump pod 161. The blood pump 13 may pump blood through the dialyzer during this period 12410.

[0149] The internal dialysate valves and pumps may be controlled to flow dialysate at zero or minimal flow across the dialyzer membrane and through the dialyzer between times 12412 and 12413. Valves 231 and 213 may be opened to allow air pressure 12450 within pump pod 162 to force clean dialysate from balancing pod 342 through the dialyzer 14 and into pump pod 162. Pump 162 may force clean dialysate from balancing pod 342 by forcing spent dialysate behind membrane 341C. Blood pump 13 may continue to pump blood through the dialyzer during this period. The pressure within pump pods 161 and 162 may be varied periodically in response to variable valves 163, 164 sinusoidally varying the size of the valve ports. The automation computer 6106 can monitor the pressure readings 12440 and 12450 to detect the end of the stroke in the dialysate pump 15 .

[0150] Dialysate can flow to the blood side of the dialyzer at the end of the dialysate pump stroke. The receiving pump pod 161 may be completely filled at time 12413, while the transfer pump 162 continues to pump fresh dialysate from the balancing pod 342 until time 12414. Dialysate from the balancing pod may not be able to enter the filled pump pod 161 and may instead flow across the dialyzer membrane and enter the blood circuit. The blood pump 13 may continue to pump blood through the dialyzer during part or all of this period. Without being bound by theory, it is believed that the flow of dialysate to the blood side of the dialyzer can displace larger solutes from the pores, center, and edges of the membrane tubes. Once displaced from the surfaces, the larger solutes are then more likely to flow through or across the membrane.

[0151] In one exemplary method, operation of the dialysate pumps 161, 162 may be stopped, and the blood pump 13 switches from one pump pod to the other if the receiving pump pod 161 is not filled. The dialysate pump may be stopped to avoid false end-of-stroke signals due to pressure signals from the switching blood pump. If the automation computer 6106 detects an end-of-stroke condition on the blood pump 13 before the receiving pump pod 161 is filled, it can close the balance chamber outlet valve 231 and the pump inlet valve 232. The valves 231 and 232 may be reopened once the blood pump is restarted. If the blood pump pod completes a stroke after the receiving pump pod 161 is filled, the blood pump waits until the transfer pump pod 162 completes its stroke. The automation computer can determine whether the pump pod stroke is complete or the dialysate pump pod is filled based on correlation coefficients for determining the end-of-stroke condition.

[0152] The pump pod pressure in the dialysate circuit can be optimally set to ensure the desired direction of dialysate and blood flow without damaging the dialyzer membrane. The pressure in the transfer pod pump 162 can be set to 54 mmHg (approximately 7.2 kPa) above the blood transfer pressure. The receiving pump pod 161 can be adjusted to 25 mmHg (approximately 3.3 kPa) above ambient pressure or the blood transfer pressure minus the transmembrane pressure, whichever is greater. The transfer pump pod pressure can be increased to the maximum transmembrane pressure of the dialyzer after filling, or after the receiving pump pod 162 is filled.

[0153] In one exemplary method, the variable valves in the blood pumps 198, 199 may cycle at a different frequency than the variable valves of the dialysate pumps 163, 164 so that end-stroke detection of each pump can be measured separately. As described elsewhere, the restrictions of the pump pod variable valves are varied sinusoidally by approximately their average value. Such small changes in restriction result in similarly small changes in the measured pressure in the drive chamber. A correlation filter, described elsewhere, provides a measurement of how well the pressure responds to the variable valve variations. The resulting correlation number can be used to determine end-stroke. Pressure fluctuations in the blood pump pod 23a may be detected by a sensor on the fill pump pod 161, which can result in an erroneous end-stroke reading. However, the correlation filter rejects pressure signals at frequencies different from the variable valve frequency. To separate the pressure signals from the two pumps 161, 23a, the variable valves may oscillate at 90% of the frequency at which the blood pump variable valves oscillate.

[0154] In one exemplary method, the delivery pump delay 12410 is optimally adjusted to deliver the desired amount of dialysate into the blood circuit at the end of the dialysate stroke. A simple proportional closed-loop controller varies the delivery pump delay 12410 to achieve the desired time for dialysate entry 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 transmembrane impedance of the dialyzer.

[0155] The following sequence is then repeated: Pump pod 162 now becomes the receiving pump, which begins the process by receiving fluid from the blood side of the dialyzer, and transfer pump 161 is stationary. Then, both pumps 161 and 162 run until receiving pump 162 is filled. At this time, pump 161 does not stop, but instead delivers dialysate to the blood side.

[0156] One exemplary method is to use pumps, valves, and balance chambers to create a small, periodic flow back and forth across the dialysis machine. Other methods and pump / valve embodiments are also contemplated.

[0157] The described hardware of the internal dialysate and blood cassette that phases the dialysate and the method of phasing the dialysate is one implementation. The same method of phasing one or more pumps on at least one side of a semi-permeable filter to periodically push fluid back and forth across the filter can be applied to the flow of fluid through other semi-permeable filters, including but not limited to ultrafilters.

[0158] In therapy, it is beneficial to keep the blood flow as constant as possible, since stagnant blood flow can lead to blood clots. Also, when the blood flow pump's transport fluid velocity is discontinuous, the balancing pump must pause its strokes frequently, which results in discontinuous and / or slow dialysate fluid velocity.

[0159] However, flow through a blood pump can be discontinuous for a variety of reasons. For example, pressure is limited within the blood pump to +600 mmHg (approximately 79.993 kPa) to -350 mmHg (approximately -46.662 kPa) to provide safe pump pressures to the patient. For example, in dual-needle flow, the two pod pumps of a blood pump can be programmed to operate 180° out of phase with each other. This phase is always achieved if there are no pressure limits. However, these pressures are limited to provide safe blood flow to the patient. If impedance is high during the fill stroke (due to small needles, very viscous blood, difficult patient access, etc.), a negative pressure limit is reached, and the fill fluid rate will be slower than the desired fill fluid rate. Therefore, the delivery stroke must wait for the previous fill stroke to complete, pausing the delivery fluid rate of the blood pump. Similarly, in single needle flow, the blood pump operates at 0° phase and the pod pumps of the two blood pumps are emptied and filled simultaneously. When both pod pumps are filled, the volume of the two pod pumps is delivered. Therefore, single needle flow is discontinuous.

[0160] One way to control the pressure saturation limit is to limit the desired fluid flow rate to the slowest of the fill and delivery strokes. This results in a slower flow rate for the blood delivery, but the flow rate is known and continuous, resulting in a more accurate and continuous dialysate flow rate. Another way to make the blood flow rate more continuous for a single needle drive is to use the maximum pressure to fill the pod so that the fill time is minimized. The desired delivery time can be set to the total time of the desired stroke minus the time taken for the fill stroke. However, if the blood flow rate cannot be kept constant, the dialysate flow rate can be adjusted to compensate for the time the dialysate pump stops when the blood flow rate for the dialysate delivery is high by a set value. If this is timed correctly, the average dialysate flow rate over multiple strokes can match the desired dialysate flow rate.

[0161] Figures 34-36 show non-limiting examples of balancing cassettes. In one configuration of the cassette, shown in Figure 34A, the valves are ganged to operate simultaneously. In one embodiment, four ganged valves 832, 834, 836, and 838 are provided. In some embodiments, the ganged valves are driven by the same air line. However, in other embodiments, each valve has a corresponding air line. In some embodiments, the ganged valves allow fluid flow as described above. In some embodiments, the ganged valves further ensure that the appropriate valves are opened and closed to create the desired fluid path.

[0162] In this embodiment, the fluid valve is a volcano valve, as disclosed in detail herein. While the fluid path outlines in various embodiments are disclosed with respect to specific flow paths, the flow paths will vary based on the actuation of the valves and pumps. Additionally, the terms inlet and outlet, as well as first and second fluid, are used (in this cassette and other cassettes described below) for descriptive purposes only. In other embodiments, the inlet may be an outlet, and further, the first and second fluids may be different fluid types or the same fluid type and composition.

[0163] Figures 35A-35E show an example top plate 1000 of a cassette. Figures 35A and 35B are plan views of the top plate 1000. In this example, the pod pumps 820, 828 and balancing pods 812, 822 of the top plate are identically formed. In this example, the pod pumps 820, 828 and balancing pods 812, 822 have a total capacity of 38 ml when assembled with the bottom plate. However, in various embodiments, the total capacity may be greater or less than that of this example. A first fluid inlet 810 and a second fluid outlet 816 are shown.

[0164] Figures 35C and 35D are bottom views of the top plate 1000. The flow paths are shown in this figure. These flow paths correspond to the flow paths in the mid-plate 900 shown in Figure 34B. The top plate 1000 and the top of the mid-plate form the liquid, or fluid, side of the cassette for the pod pumps 820, 828 and on one side of the balancing pods 812, 822. Therefore, most of the fluid flow paths are located in the top plate and mid-plate. The other side of the balancing pods 812, 822 is located on the inside of the bottom plate, as shown in Figures 36A and 36B, but not shown here.

[0165] Figures 35C and 35D further illustrate that the pod pumps 820, 828 and balancing pods 812, 822 include grooves 1002. The grooves 1002 shown have a predetermined shape. However, in other embodiments, the shape of the grooves 1002 can be any desired shape. Figures 35C and 35D illustrate an example shape. In some embodiments, the grooves 1002 form passageways between the fluid inlet and fluid outlet sides of the pod pumps 820, 828 and balancing pods 812, 822.

[0166] The grooves 1002 provide a flow path, and because there is a flow path between the inlet and outlet when the septum is at the end of the stroke, pockets of fluid or air are not trapped in the pod pumps or balancing pods. The grooves 1002 are included on both the liquid and air sides of the pod pumps 820, 828 and balancing pods 812, 822 (see Figures 36A and 36B, which relate to the air sides of the pod pumps 820, 828 and the opposite sides of the balancing pods 812, 822).

[0167] In one embodiment, the liquid sides of the pod pumps 820, 828 and balancing pods 812, 822 include a feature that allows the inlet and outlet flow paths to be continuous and the outer ring 1004 to be continuous. This feature allows a seal (not shown) to be formed against the septum to be retained.

[0168] 35E is a side view of an embodiment of the top plate 1000. The continuous outer ring 1004 of the pod pumps 820, 828 and balancing pods 812, 822 are shown. Figures 36A-36E show the bottom plate 1100. Figures 36A and 36B show the inner surface of the bottom plate 1100. The inner surface is the side that contacts the bottom surface of the mid-plate (not shown here), shown in Figure 34E. The bottom plate 1100 is attached to an air line (not shown). Corresponding inlet holes 1106 for air to actuate the pod pumps 820, 828 and valves (not shown here), shown in Figure 34E, are provided in the mid-plate. Holes 1108, 1110 correspond to the second fluid inlet 824 and second fluid outlet 826, respectively, shown in Figure 34C. Also shown are grooves 1112 for fluid paths in the pod pumps 820, 828 and the corresponding halves of the balancing pods 812, 822. Unlike the top plate, the halves of the bottom plate corresponding to the pod pumps 820, 828 and balancing pods 812, 822 clearly distinguish between the pod pumps 820, 828 and balancing pods 812, 822. The pod pumps 820, 828 have air passages in the second half of the bottom plate, while the balancing pods 812, 822 have identical structures as their top half. Additionally, the balancing pods 812, 822 maintain fluid balance, whereby both sides of a bulkhead (not shown) contain liquid flow paths, and the pod pumps 820, 828 are pressure pumps that pump liquid, whereby one side contains liquid flow paths and the other side, shown in the bottom plate 1100, contains an air-driven chamber or air fluid path.

[0169] In one embodiment of the cassette, sensor elements are incorporated into the cassette to detect various properties of the pumped fluid. In one embodiment, three sensor elements are included. In one embodiment, the sensor elements are located in a sensor cell 1114. Cell 1114 houses three sensor elements in sensor element housings 1116, 1118, and 1120. In one embodiment, two of sensor housings 1116 and 1118 house conductivity sensor elements, and the third sensor element housing 1120 houses a temperature sensor element. The conductivity sensor element and temperature sensor element may be any conductivity sensor element or temperature sensor element known in the art. In one embodiment, the conductivity sensor element is a graphite post. In another embodiment, the conductivity sensor element is formed from stainless steel, titanium, platinum, or other metals that are coated for corrosion protection but still have electrical conductivity. The conductivity sensor element may include electrical wiring for transmitting 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, only temperature sensors, one or more conductivity sensors, or one or more other types of sensors. In some embodiments, the sensor elements may be located outside the cassette, in a separate cassette, or connected to the cassette by a fluid line.

[0170] Figures 36A and 36B also show the drive side of metering pump 830, as well as the corresponding air inlet hole 1106 for air to power the pump. Figures 36C and 36D show the outside of bottom plate 1100. Air line connection points 1122 for valves, pod pumps 820, 828, and metering pump 830 are shown. Again, balancing pods 812, 822 do not have air line connection points and are therefore not air powered. Also shown are corresponding openings in bottom plate 1100 for second fluid outlet 824 and second fluid inlet 826.

[0171] Figure 36E is a side view of bottom plate 1100. In the side view, a lip 1124 surrounds the inner bottom plate 1100. The lip 1124 is raised and continuous, providing a connection point for a bulkhead (not shown). The bulkhead rests on this continuous raised lip 1124, thereby creating a seal between the pod pumps 820, 828 and half of the balancing pods 812, 822 on the bottom plate 1100 and the pod pumps 820, 828 and half of the balancing pods 812, 822 on the top plate (not shown here) shown in Figures 35A-35D.

[0172] As described above, dialysate flows from the directing circuit, optionally through a heater and / or an ultrafiltration membrane, to the balancing circuit. In some embodiments, the directing circuit is provided in the cassette, although not necessarily. FIG. 3A shows directing circuit 142 as an example of a directing circuit. Directing circuit 142 can perform several different functions in this example. For example, dialysate flows from a dialysate supply (such as from a mixing circuit, as described below) through the directing circuit to the balancing circuit, and used dialysate flows from the balancing circuit to drain. Dialysate flows by driving one or more pumps included in the directing circuit. In some embodiments, the directing circuit includes a dialysate tank, which contains dialysate prior to moving the dialysate to the balancing circuit. The dialysate tank, in some embodiments, allows the dialysate production rate to differ from the dialysate usage rate of the dialyzers in the system. The directing circuit also directs water from the water supply to the mixing circuit (if one is present). Additionally, as described above, the blood flow circuit communicates with the directing circuit for operations such as disinfection.

[0173] Thus, in some embodiments, dialysate is prepared on demand, eliminating the need to store large amounts of dialysate. For example, the dialysate is prepared and then held in a dialysate tank 169. A dialysate valve 17 controls the flow of dialysate from the tank 169 to the dialysate circuit 20. The dialysate is filtered and / or heated before being sent to the dialyzer 14. A contaminant treatment valve 18 is used to control the flow of used dialysate from the dialysate circuit 20.

[0174] FIG. 6 shows an example of a directing circuit, but it is not limited thereto. In this figure, directing circuit 142 communicates dialysate from the dialysate supply through dialysate pump 159, heater 72, and ultrafiltration membrane 73, as described above, to dialysate tank 169 before entering the balancing circuit. As shown, the dialysate in the dialysate flow path flows from the dialysate supply to the dialysate tank, pump, heater, and ultrafiltration membrane (in that order), although other orders are possible in other examples. Heater 72 is used to heat the dialysate to body temperature and / or to heat the blood in the blood flow circuit so that the blood returned to the patient is at body temperature. Ultrafiltration membrane 73 is used to remove pathogens, pyrogens, etc. from the dialysate, as described below. The dialysate flows through the balancing circuit and is then directed to the dialyzer.

[0175] The dialysate tank 169 may be made of any suitable material and may be of any suitable size for storing dialysate prior to use. For example, the dialysate tank 169 may be made of plastic, metal, etc. The dialysate tank may be made of materials similar to those used to form the pod pumps, as described above.

[0176] The flow of dialysate through directing circuit 142 is controlled (at least in part) by operation of dialysate pump 159. Additionally, dialysate pump 159 controls flow through the balancing circuit. For example, as described above in FIG. 5, fresh dialysate from the directing circuit flows to balancing chambers 341 and 342 of balancing circuit 143. Pump 159 is used to force fresh dialysate through these balancing chambers. In an embodiment, dialysate pump 159 comprises a pod pump similar to those described above. The pod pump includes rigid chambers with flexible diaphragms separating each chamber into a fluid compartment and a control compartment. The control compartment is connected to a source of controlled fluid, such as an air source. Examples of pod pumps and pumps used as balance chambers are disclosed, but not limited to, in U.S. patent application Ser. No. 60 / 792,073, filed April 14, 2006, and entitled "Extracorporeal Thermotherapy System and Method," or U.S. patent application Ser. No. 11 / 787,212, filed April 13, 2007, and entitled "Fluid Pumping System, Apparatus, and Method," both of which are incorporated herein in their entireties. Pod pumps are described in further detail below.

[0177] After passing through pump 159, the dialysate flows to a heater, such as heater 72 of FIG. 6. The heater may be any suitable heating device for heating the dialysate, such as an electrical resistance heater, as known to those skilled in the art. The heater may be separate from the directing circuit, as shown in FIG. 3A, or the heater may be incorporated into the directing circuit or into another circuit (e.g., the balancing circuit).

[0178] In some embodiments, the dialysate is heated to a temperature that prevents the blood passing through the dialyzer from becoming cold. For example, the temperature of the dialysate is controlled so that the dialysate is at or above the temperature of the blood passing through the dialyzer. In the above example, the blood is heated somewhat as described above to offset heat loss caused by the blood passing through various elements of the blood flow circuit. Additionally, as described below, in some embodiments, the heater is coupled to a control system so that incorrectly heated dialysate (i.e., dialysate that is too heated or too cold) is recirculated (e.g., back to the dialysate tank) instead of passing through the dialyzer via line 731. The heater may be integrally formed as part of a fluid circuit, such as a directing circuit or balancing circuit, or, as shown in FIG. 3A, the heater may be a separate element within the dialysate flow path.

[0179] In some embodiments, heaters are also used for disinfection or sterilization. For example, water passing through a hemodialysis system is heated using a heater to a temperature suitable for disinfection or sterilization, e.g., 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 embodiments, the water is recirculated through various elements, as described below, and / or heat loss within the system is minimized by using a heater to heat the water to the disinfection or sterilization temperatures described below.

[0180] The heater includes a control system that can control the heater as described above (e.g., heating the dialysate to body temperature for dialyzing the patient, heating the water temperature to a disinfecting temperature for purifying the system).

[0181] Non-limiting examples of heater controllers are described below. The controller is selected to handle pulsating flow rates and various fluid velocities, as well as various inlet fluid temperatures. Additionally, the heater control must function properly when flow is directed to each of the different flow paths (dialysis, disinfection, recirculation, etc.). In one embodiment, the heater controller is used on the SIP1 board, with an IR (infrared) temperature sensor on the ultrafiltration membrane and an IR temperature sensor on the tank. In another embodiment, the board is located in a box with less heat loss and uses a conductivity sensor for the inlet temperature sensor. In another embodiment, the controller is a simple proportional controller that uses the temperatures of both the tank (heater inlet) and the ultrafiltration membrane (heater outlet). For example: powerHeater=massFlow*((tankPGain*errorTank)+(UFPGain*errorUF) PowerHeater = Heater usage rate command (0 to 100%); MassFlow = fluid mass flow rate;TankPGain = proportional gain for tank or inlet temperature sensor; ErrorTank = Difference between tank or inlet temperature sensor and desired temperature; UFPGain = proportional gain for the ultrafiltration membrane or outlet temperature sensor; ErrorUF=uf or difference between outlet temperature sensor and desired temperature.

[0182] A PWM command is generated from the heater duty cycle command (0-100%). In an embodiment, the controller reduces the mass flow rate if the desired temperature is not maintained and the heater becomes saturated. Heater Control In the alternative embodiment of heater 72 in FIG. 122, the dialysate flow path may be provided such that the electric heater element and heater temperature sensor are supplemented by temperature sensors located in the flow path upstream and downstream of the heater. Temperature sensor 254 is located immediately upstream of the heater to provide information about the temperature of the incoming fluid. Redundant temperature sensors 252 and 251 are located downstream of ultrafiltration membrane 73 to measure the temperature of the dialysate entering the internal dialysate cassette. Temperature sensor 255 may be located in line 731 to measure the flow diverting from the internal cassette.

[0183] Referring to FIG. 123A, in an alternative embodiment, a "heater control mode" comprises a control loop 608 around the heater. In one embodiment, the heater control mode uses a closed-loop controller, a simple proportional-integral controller, to drive the heater temperature 612 to the desired temperature 610 by outputting a duty cycle command to the heater 72. 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 conduit within the heater 72. The heater temperature sensor may be embedded within the heater 72. The duty cycle command may be converted to a pulse-width modulated ("PWM") command with a fundamental frequency of 1 Hz. The heater current may be controlled by the PWM command using an SCR electronic component that switches on and off at zero crossings. The heater current may be controlled by a transistor switch (such as a FET, IGBT, or BJT). Assuming a 60 Hz power line frequency, a PWM frequency of 1 Hz allows for a resolution of 1 in 60.

[0184] The heater duty cycle command may have a lower limit of 0. The heater can be configured to run at 100% duty cycle or at a reduced duty cycle. The maximum duty cycle may be limited by available power. In one example, the heater's maximum duty cycle may be 70% for a total current draw of 8 amps, which allows adequate power to run the remaining components in the dialysis machine 6001. In another example, the maximum total current draw is 11 amps, and the heat duty cycle is limited to 100%. A user or professional can set the maximum duty cycle of the heater controller and the maximum power draw of the dialysis machine 6001 (shown in block form in FIG. 61) by selecting a high or low power setting via software. A lower power setting may allow the dialysis machine 6001 to be connected to the same circuit as a machine that prepares water for the dialysis machine 6001. The maximum heater command may be limited by a saturation block 619 shown in FIGS. 123A-123C. The maximum flow rate through the heater may be controlled based on the inlet temperature 254 and the available power to create a dialysate that achieves the minimum allowable dialysate temperature measured by sensors 251, 252.

[0185] The heater controller is considered asymmetric in nature because it can increase the heater temperature by using more power, but decrease the heater temperature by heat loss to the atmosphere or flowing dialysate. The control loop of FIG. 123A can operate with different integral and proportional gains 618, 616 to accommodate different levels of heat loss due to external factors, including but not limited to room temperature, incoming dialysate temperature, and dialysate fluid velocity.

[0186] The heater control mode may select different gains depending on the operating mode selected in the therapy application 6203 (FIG. 62). When an operating mode is selected that requires a high rate of fluid flow through the heater, the gains 616, 618 may be set high. When an operating mode is selected that requires a low rate of fluid flow through the heater, the gains 616, 618 may be set low. To prevent temperature overshoot, the gains may be set to a minimum or zero value when there is no flow through the heater during this mode. Because disinfection temperatures can be near the limits of material temperature and the large temperature rises associated with thermal disinfection are more likely to cause temperature overshoot, the gains 616, 618 may be set low during the disinfection operating mode to prevent overshoot at high temperatures.

[0187] A saturation block 619 can limit the output 614 of the heater control loop 608 to the output of a maximum heater utilization, which in a preferred embodiment is selectable between about 70% and about 100%.

[0188] In another example, the integrator value 620 may be limited to prevent temperature overshoot. If the heater command is at its upper limit, the integrator value 620 may not be increased until the heater command is below the upper limit. The integrator value may be decreased at any time.

[0189] To minimize heater temperature fluctuations when fluid flow through the heater is temporarily stopped, the heater control mode can temporarily suspend heater operation and save one or more control parameters to memory. In a preferred embodiment, when fluid flow through the heater is stopped for a short period of time, the heater can be turned off and the integrator value 620 can be saved. The heater can then be turned back on with the gains 616, 618 appropriate for the operating mode and the integrator value reloaded from memory.

[0190] An alternative embodiment of the heater controller, referred to as the "fluid temperature control mode," is shown in FIG. 123B. The fluid temperature control mode can add an outer control loop 638 around the inner control loop 608 of the heater control mode. The outer control loop 638 can drive the actual fluid temperature 632 to the desired fluid temperature 630 by varying the desired heater temperature 610. The fluid temperature control mode feeds this desired heater temperature 610 to the inner control loop 608, which generates a signal 614 for controlling the heater as described above in the heater control mode. The inner control loop may include modifying gains 616, 618 based on the operating mode of the dialysis unit and limiting the integrator when the heater command reaches a maximum allowable value. The fluid temperature control mode may include the following feedforward command (ffCmd) 642 based on the desired temperature 630, inlet fluid temperature 254, fluid flow rate, and gain factor:

[0191]

number

[0192]

number

[0193] The fluid temperature control mode may select different gains 636, 638 depending on the operating mode selected in the therapy application 6203 (FIG. 62). When the operating mode requires a high rate of fluid flow through the heater 72, the gains 636, 638 may be set high. When the operating mode requires a low rate of fluid flow through the heater 72, the gains 636, 638 may be set low. To prevent temperature overshoot, the gains may be set to a minimum or zero value when there is no flow through the heater 72 during the mode.

[0194] The fluid temperature control mode can limit the integrator value 640 to avoid temperature overshoot. If either the heater command 614 or the desired heater temperature 610 are at their maximum allowed values, the integrator value 640 may not be increased until both the heater command and desired heater temperature drop below their upper limits. The integrator value may be decreased at any time.

[0195] The fluid temperature control mode may optionally vary the rate of dialysate fluid from the external pump 159 to maintain the dialysate within desired temperature limits. If either the heater command 614 or the desired heater temperature 610 are at their maximum allowable values ​​for a predetermined minimum period, the dialysate fluid rate may be reduced to a rate of, for example, approximately 30 ml / min per stroke. If both the heater command and desired heater temperature fall below their upper limits for a predetermined minimum period, the desired flow rate may be increased to a rate of, for example, 30 ml / min until the flow rate returns to its original, planned value. In a preferred embodiment, the minimum period is set to the time to complete the current and previous strokes. The fluid temperature control mode uses the minimum period to create a smoother temperature response and reduce temperature overshoot. The flow through the heater may be limited to a predetermined minimum value. In a preferred embodiment, the minimum flow rate of dialysate through the heater, as measured by the external pump, is set to approximately 100 ml / min.

[0196] To minimize heater temperature fluctuations when fluid flow through the heater is stopped for a short period of time, the fluid temperature control mode is programmed to suspend heater operation and save one or more control parameters to memory. Fluid flow may be stopped periodically to allow the dialysis unit to perform functional checks, including dialysate level and fluid valve performance. In a preferred embodiment, when fluid flow through the heater is stopped for a short period of time, the heater is turned off and the dialysate fluid rate and integrator values ​​640, 620 are saved to memory. When flow resumes, the integrator values ​​and dialysate fluid rate are reloaded from memory, the heater is turned back on, and the gains 616, 618, 636, 638 are set depending on the operating mode.

[0197] In an alternative embodiment, as shown in FIG. 123C, the heater controller has a "heater only power mode" consisting of a control loop 648 around the heater. The heater only power mode can use a simple proportional-integral controller to drive a heater temperature 612 to a heater setpoint temperature 610 by outputting 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 several parameters, such as a measured inlet fluid temperature 647, a desired fluid temperature 611, an estimated fluid mass flow, and a gain factor. In a preferred embodiment, the feedforward signal 646 can be calculated as follows:

[0198]

number

[0199]

number

[0200] The heater temperature 612 may be measured by a heater temperature sensor. The inlet temperature is measured by sensor 254. The duty cycle command may be converted to a PWM command, which in one embodiment has a fundamental frequency of about 1 Hz. The heater current may be controlled by the PWM command using an SCR electronic component that turns on and off at zero crossings, or by a transistor switch such as a FET, IGBT, or BJT. Assuming a 60 Hz power line frequency, a 1 Hz PWM frequency allows for a resolution of 1 in 60.

[0201] The lower limit of the heater duty cycle command can be set to 0. The heater can be configured to run at 100% duty cycle or at a reduced duty cycle. The maximum duty cycle may be limited by available power. In a preferred embodiment, the maximum duty cycle is set to approximately 70%, limiting the total current draw to 8 amps, which should allow power to run the remaining components in the dialysis machine 6001. Alternatively, the maximum total current draw is set to 11 amps, limiting the heat duty cycle to 100%. A user or professional can set the maximum duty cycle of the heater controller and the maximum power consumption of the dialysis machine 6001 by selecting a high or low power setting via software. A lower power setting may allow the dialysis machine 6001 to be connected to the same electrical circuit as a machine that prepares water for the dialysis machine 6001. Depending on the available power, the maximum flow rate through the heater may be controlled by monitoring the inlet temperature 254 so that the prepared dialysate achieves the minimum allowable dialysate temperature as measured by sensors 251 and 252.

[0202] The heater-only power mode may select different gains depending on the operating mode selected in the therapy application 6203 (FIG. 62). When an operating mode is selected that requires a high rate of fluid flow through the heater, the gains 616, 618 may be set high. When an operating mode is selected that requires a low rate of fluid flow through the heater, the gains 616, 618 may be set low. To prevent temperature overshoot, the gains may be set to a minimum or zero value when there is no flow through the heater during this mode. Because disinfection temperatures may approach material temperature limits and large temperature increases are more likely to cause temperature overshoot, the gains 616, 618 may be set low during the disinfection operating mode to prevent temperature overshoot.

[0203] Another method for avoiding temperature overshoot involves limiting the integrator value 620. When the heater command is at its upper limit, the integrator value 620 is prevented from increasing until the heater command is below the upper limit. The integrator value can be decreased at any time.

[0204] To minimize heater temperature fluctuations when fluid flow through the heater is temporarily stopped, the heater-only power mode can temporarily suspend heater operation and save one or more control parameters to memory. In a preferred embodiment, when fluid flow through the heater is stopped for a short period of time, the heater can be turned off and the integrator value 620 can be saved to memory. The heater can then be turned back on with the gains 616, 618 set depending on the operating mode by reloading the integrator value from memory.

[0205] In one embodiment of the heater controller, several safety checks are performed during start-up to verify the functionality of the heater system, including the heater function, temperature sensor, and control electronics. Start-up safety checks may include verifying that the output of the temperature sensor is within an expected range. In one embodiment, the expected range for the temperature sensor is 0°C to 110°C.

[0206] To verify that the heater can be turned on and off, a start-up safety check may include a heater system test that turns the heater on for a short period and continues to monitor the heater temperature sensor during this on period followed by a longer off period. The test may require that the heater sensor value increase during the on period and not continue to increase during the off period. In a preferred embodiment, the heater is turned on for approximately 5 seconds, and the temperature sensor is monitored during the 5-second on period followed by a 20-second off period. In one embodiment, the test passes if the heater temperature increases by at least approximately 1.0°C and by more than approximately 6.0°C.

[0207] During operation of the dialysis unit, the heater temperature is monitored when the heater command 614 is at its maximum value to ensure proper heater function. To pass this test, the heater temperature is expected to increase by a predetermined amount over a specified period of time. In a preferred embodiment, the heater temperature is expected to increase by more than approximately 0.5°C over a one-minute period. This test can be performed while a patient is connected to the dialysis unit during operation mode.

[0208] Safety testing may monitor the heater temperature during all operations to avoid excessive fluid temperatures. If the heater temperature 612 exceeds the maximum allowable heater temperature during a given mode of operation, the heater and heater controller are disabled. In a preferred embodiment, during patient-connected operation, the maximum heater temperature is set at approximately 70°C. During disinfection mode, the maximum heater temperature is set at a higher temperature, such as approximately 100-110°C. The heater may also include a secondary safety system consisting of a thermal fuse on the heater.

[0209] A safety test can monitor two or more of the fluid temperature sensors and disable the heater 14 and heater controller if any one of the temperature sensors exceeds the maximum disinfectant fluid temperature. Preferably, all fluid temperature sensors 251, 252, 254, 255 are monitored with the maximum disinfectant fluid temperature set at approximately 100° C. One benefit of this test is that it protects against a single fluid temperature sensor failure or heater temperature sensor failure.

[0210] 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. The heater 72 and controller may be disabled in fluid temperature control mode if the external pump controller detects a blockage or air leak.

[0211] The heater controls described above are exemplary only, and it is understood that other heater control systems and other heaters are possible in alternative embodiments of the invention. The dialysate may be further filtered to remove contaminants, infectious organisms, pathogens, pyrogens, debris, etc., using, for example, an ultrafiltration membrane. The filter may be placed in a suitable location in the dialysate flow path, between the directing circuit and the balancing circuit, as shown in FIG. 3A, and / or the ultrafiltration membrane may be incorporated into either the directing circuit or the balancing circuit. When an ultrafiltration membrane is used, it is selected to have a mesh size that prevents the above types of particles from passing through the filter. For example, the mesh size may be about 0.3 micrometers or less, about 0.2 micrometers or less, about 0.1 micrometers or less, or about 0.05 micrometers or less. Those skilled in the art will recognize that filters such as ultrafiltration membranes are often readily available commercially.

[0212] In some embodiments, the ultrafiltration membrane is operated such that contaminants from the filter (e.g., the retentate stream) are transferred to a contaminant stream, such as contaminant line 39 in FIG. 6 . In some embodiments, the amount of dialysate flowing in the retentate stream can be controlled. For example, if the retentate is too cold (i.e., heater 72 does not operate or heater 72 does not heat the dialysate to a sufficient temperature), the entire dialysate stream (or at least a portion of the dialysate) is diverted to contaminant line 39 and, optionally, recycled to dialysate tank 169 using line 48. The flow from the filter may be further monitored for various reasons, such as using temperature sensors (e.g., sensors 251 and 252), conductivity sensors (to verify dialysate concentration, e.g., sensor 253), etc. Examples of such sensors are described below. Other examples are disclosed, but not limited to, in U.S. patent application Ser. No. 12 / 038,474, entitled "Sensor Apparatus, Systems, and Methods" (Docket No. F63). This document is incorporated herein in its entirety.

[0213] The ultrafiltration membrane and dialyzer are redundant screening methods for removing contaminants, infectious organisms, pathogens, pyrogens, and debris (although in other cases the ultrafiltration membrane is not provided). Therefore, for contaminants to reach the patient from the dialysate, the contaminants must pass through both the ultrafiltration membrane and the dialyzer. If one cannot filter, the other can still sterilize and prevent the contaminants from reaching the patient's blood.

[0214] Directing circuit 142 can further direct spent dialysate through a balancing circuit to a drain, e.g., contaminant line 39 to drain 31 in FIG. 6. The drain can be, for example, a local drain or a separate container for containing contaminants (e.g., spent dialysate) to be suitably located. In some embodiments, one or more check valves or "one-way" valves (e.g., check valves 215 and 216) are used to control the flow of contaminants from the directing circuit and the system. Additionally, in some embodiments, a blood leak sensor (e.g., sensor 258) is used to determine whether blood is leaking through the dialyzer into the dialysate flow path.

[0215] The drain 31 (FIG. 89) may include an air-in-line (AIL) detector 37 to monitor the balancing and directing circuits for leaks and septum ruptures. The dialysate flowing past the AIL detector 37 has previously flowed through the pump in the directing cassette, the balancing chamber and pump in the balancing cassette, and several valves. If there is a leak in any of the valves or pod pump septa, the leaked air will flow past the AIL detector in the drain 31. The AIL detector 37 can also detect gases evolved from the dialysate, possibly as it is heated. In a preferred embodiment, all detectors 37 are located on the drain 31 with an upward flow. This potentially advantageous location facilitates detection of air bubbles flowing with the dialysate, as the drain (which may be configured to any suitable extent) provides ample opportunity for the bubbles to collect before reaching the detector 37. The AIL detector 37 is positioned on the drain 31, allowing the detector to distinguish between a septum rupture and an air bubble.

[0216] Additionally, directing circuit 142 receives water from water supply 30, e.g., a water container such as a bag, and / or from a device capable of producing water, such as a commercially available reverse osmosis device. In an embodiment, as known to those skilled in the art, water entering the system is set to a predetermined purity, e.g., has an ion concentration below a predetermined value. Water entering directing circuit 142 travels to various locations, e.g., to a mixing circuit for producing fresh dialysate and / or to contaminant line 39. As described below in an embodiment, valves to drain 31 and various recirculation lines are opened, and conduit 67 is connected between directing circuit 142 and blood flow circuit 141 to allow water to flow continuously throughout the system. If heater 72 is also activated, water passing through the system is continuously heated to a temperature sufficient to disinfect the system. This disinfection method is described in more detail below.

[0217] Non-limiting examples of balancing cassettes are shown in Figures 41-45. Figures 41A and 41B show the exterior of the top plate 900 of one embodiment of the cassette. Top plate 900 contains one half of the pod pumps 820, 828. This half is the fluid or liquid source half through which the source flow flows. Inlet and outlet pod pump flow paths are shown. These flow paths lead to each pod pump 820, 828.

[0218] The pod pumps 820, 828 include elevated flow paths 908, 910. The elevated flow paths 908, 910 allow fluid to continue flowing through the pod pumps 820, 828 after a diaphragm (not shown) reaches the end of the stroke. Thus, the elevated flow paths 908, 910 minimize diaphragms that could trap air or fluid in the pod pumps 820, 828 or block the inlets or outlets of the pod pumps 820, 828, preventing flow. In this embodiment, the elevated flow paths 908, 910 have predetermined dimensions. In alternative embodiments, the elevated flow paths 908, 910 are larger or narrower. In yet another embodiment, the elevated flow paths 908, 910 can be any size, as long as the goal is to control the flow rate to obtain a desired fluid velocity or drive a desired amount of fluid. Therefore, any dimensions disclosed herein for raised channels, pod pumps, valves, or other aspects are exemplary and are merely alternative embodiments. Other embodiments will be apparent. Figures 41C and 41D show the inside of the top plate 900 of this embodiment of the cassette. Figure 41E is a side view of the top plate 900.

[0219] Figures 42A and 42B show the fluid or liquid side of the midplate 1000. Figures 41C and 41D show the areas that complement the flow channels on the inner top plate. These areas are slightly raised to show the conductive surface finish provided by laser welding, one mode of manufacture in this embodiment. Other modes of cassette manufacture have been described above.

[0220] Figures 42C and 42D show the air side of midplate 1000 in this embodiment, or the side that faces the bottom plate (not shown here) shown in Figures 43A-43E. Valve holes 802, 808, 814, 816, 822, 836, 838, 840, 842, 844, and 856 on the air side correspond to the holes on the fluid side of midplate 1000 shown in Figures 42A and 42B. As shown in Figures 44C and 44D, diaphragm 1220 completes pod pumps 820 and 828, and diaphragm 1222 completes 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 actuated by air pressure, and when the septum is pulled away from the hole, liquid or fluid flows. When the septum is pressed toward the hole, fluid flow is prevented. Fluid flow is directed by opening and closing valves 802, 808, 814, 816, 822, 836, 838, 840, 842, 844, and 856. Figures 43A and 43B show views of the inside of bottom plate 1100. The interior of pod pumps 820 and 828 and the actuation or air chambers of valves 802, 808, 814, 816, 822, 836, 838, 840, 842, 844, and 856 are shown. The pod pumps 820, 828 and valves 802, 808, 814, 816, 822, 836, 838, 840, 842, 844, 856 are driven by an air source. Figures 43C and 43D show the outside of the bottom plate 1100. The air source is attached to this side of the cassette. In one embodiment, tubing is connected to the valves and tubing of the pump 1102. In some embodiments, the valves are ganged and multiple valves are driven by the same air line.

[0221] An assembled cassette 1200 is shown in Figures 44A and 44B. An exploded view of the assembled cassette 1200 shown in Figures 44A and 44B is shown in Figures 12C and 12D. In these figures, an embodiment of a pod pump diaphragm 1220 is shown. The diaphragm gasket seals between the liquid chamber (in the top plate 900) and the air or drive chamber (in the bottom plate 1100). In some embodiments, the dome texture of the diaphragm 1220 provides additional space for air and liquid to escape the chamber, especially at the end of the stroke. In alternative embodiments of the cassette, the diaphragm includes a double gasket. The double gasket feature in preferred embodiments exists when both sides of the pod pump contain liquid, or when sealing both sides of the chamber is desired. In these embodiments, a lip complementary to the gasket or other feature (not shown) is added to the interior bottom plate 1100, whereby the gasket seals the pod pump chamber in the bottom plate 1100.

[0222] 45 is a cross-sectional view of the cassette pod pump 828, showing details of the attachment of the bulkhead 1220. Again, in this embodiment, the gasket of the bulkhead 1220 is sandwiched by the mid-plate 1000 and bottom plate 1100. The edge of the mid-plate 1000 has features that allow the gasket to seal the chamber of the pod pump 828 attached to the top plate 900.

[0223] Figure 45 is a cross-sectional view of valves 834, 836 of the assembled cassette, showing the septum 1220 assembled and positioned by sandwiching it between the mid-plate 1000 and the bottom plate 1100 in this embodiment. Additionally, the cross-sectional view of Figure 45 shows valve 822 of the assembled cassette, showing the septum 1222 positioned by sandwiching it between the mid-plate 1000 and the bottom plate 1100.

[0224] In some embodiments, dialysate is prepared separately and delivered to the system for use in the directing circuit. However, in some embodiments, the dialysate is prepared in the mixing circuit. The mixing circuit operates to form the dialysate at a suitable time. For example, the dialysate may be produced during and / or prior to dialysis of a patient (e.g., the dialysate may be contained in a dialysate tank). To form the dialysate in the mixing circuit, water (e.g., from a water supply, optionally provided to the mixing circuit by the directing circuit) is mixed with various dialysate ingredients. For example, those skilled in the art will know suitable dialysate ingredients, such as sodium bicarbonate, sodium chloride, and / or acid, as described above. Because the dialysate is formed on demand, it may be contained in the dialysate tank in certain cases, but not necessarily in large quantities.

[0225] FIG. 7A illustrates an exemplary, non-limiting example of a mixing circuit that may be provided in a cassette in accordance with an embodiment. In FIG. 7A, water from the directing circuit flows into mixing circuit 25 driven by pump 180. In some embodiments, a portion of the water is delivered to source 49, for example, for use in transporting ingredients through the mixing circuit. As shown in FIG. 7A, water is delivered to bicarbonate source 28 (which, in some embodiments, also contains sodium chloride). In some embodiments, sodium chloride or sodium bicarbonate is provided in powder or granular form, displaced by the action of water. Bicarbonate from bicarbonate source 28 is delivered by bicarbonate pump 183 to mixing line 186, which also contains water from the directing circuit. Acid (in the form of a fluid) from acid source 29 is also pumped into mixing line 186 by acid pump 184. The ingredients (water, bicarbonate, acid, sodium chloride, etc.) are mixed in mixing chamber 189 to form the dialysis fluid that flows from mixing circuit 25. Conductivity sensors 178 and 179 are provided along the mixing line 186 to ensure that the ingredients are added at the appropriate concentrations when they are added to the mixing line. This method and its control to ensure acceptable dialysate quality is produced and maintained throughout treatment is described in more detail below.

[0226] In some embodiments, pump 180 comprises one or more pod pumps similar to those described above. Pod pumps include rigid chambers with flexible partitions separating each chamber into a fluid compartment and a control compartment. The control compartment is connected to a source of controlled fluid, such as an air source. Examples of pod pumps are disclosed, but not limited to, in U.S. patent application Ser. No. 60 / 792,073, filed April 14, 2006, and entitled "Extracorporeal Thermal Therapy System and Method," or U.S. patent application Ser. No. 11 / 787,212, filed April 13, 2007, and entitled "Fluid Pump System, Apparatus, and Method," both of which are incorporated herein by reference in their entireties. Similarly, in some embodiments, pumps 183 and / or 184 are each pod pumps. Pod pumps are described in further detail below.

[0227] In some embodiments, one or more pumps have a pressure sensor that monitors the pump pressure to ensure the pump compartment is completely filled and delivered. For example, to ensure the pump delivers a full stroke of fluid, (i) fill the compartment, (ii) close both fluid valves, (iii) apply pressure to the compartment by opening a valve between the positive air tank and the compartment, (iv) close the positive pressure valve, leaving pressurized air in the passage between the valve and the compartment, (v) open the fluid valve, allowing fluid to flow from the pump compartment, and (vi) monitor the pressure drop in the compartment as fluid flows from the pump compartment. The pressure drop corresponding to a full stroke is consistent and depends on the initial pressure, the volume occupied between the valve and the compartment, and / or the stroke volume. However, in other embodiments of the pod pump disclosed herein, a reference volume compartment is used, and the volume is defined by pressure and volume data.

[0228] Since the volume delivered by the water pump or other pumps is directly related to the conductivity measurement, the volume measurement is used as a cross-check on the composition of the dialysate being formed, thereby ensuring that the dialysate composition remains safe even in the event of inaccurate conductivity measurements during treatment.

[0229] FIG. 7B is a schematic diagram illustrating another example of a mixing circuit that may be provided in an embodiment of the cassette. The mixing circuit 25 in this figure includes a pod pump 181 that pumps water from a water supply along line 186. Various ingredients for making the dialysate are introduced into the water. Another pump 182 pumps sodium bicarbonate from the water supply to a source 28 (e.g., a container) containing sodium bicarbonate and / or sodium chloride to a source 188 containing sodium chloride. A third pump 183 introduces dissolved bicarbonate into the mixing line 186 (where they are mixed in mixing chamber 189), and a fourth pump 185 introduces dissolved sodium chloride into the line 186 (where they are mixed in mixing chamber 191). A fifth pump 184 introduces acid into the water prior to passing through the first pump 181. Mixing is monitored using conductivity sensors 178, 179, and 177. Each conductivity sensor measures the conductivity of a given ingredient after it is added to the mixing line 186 to ensure that the proper amount and concentration of ingredient has been added. Examples of such sensors are described below. Further examples are disclosed, but are not limited to, in U.S. patent application Ser. No. 12 / 038,474, Docket No. F63, entitled "Sensor Apparatus System, Apparatus and Method," which is incorporated herein by reference in its entirety. This method and its control to ensure acceptable dialysate quality is formed and maintained throughout treatment are described in more detail below.

[0230] FIG. 3B shows that in this embodiment, mixing circuit 25 uses two sources to make up the dialysate: a source of acid concentrate 27 and a combined source of sodium bicarbonate (NaHCO3) and sodium chloride (NaCl). In the embodiment shown in FIG. 3B, dialysate making up system 25 includes multiples of each source. In the embodiment, the system is continuously powered, with redundant dialysate sources allowing the system to function continuously, so that when one set of sources is depleted, the system can use the redundant sources and replace the first set of sources. This process is repeated as necessary, for example, until the system shuts down.

[0231] Non-limiting examples of balancing cassettes are shown in Figures 34-36. In the fluid flow cassette shown in Figure 37, the valves are each open. In this example, the valves are opened by air pressure. Furthermore, in this example, the fluid valves are volcano valves, as disclosed in detail herein.

[0232] 38A and 38B show the top plate 1100 of the cassette in one embodiment. In this embodiment, the pod pumps 820, 828 and mixing chamber 818 of the top plate 1100 are similarly formed. In this embodiment, the pod pumps 820, 828 and mixing chamber 818, when assembled with the bottom plate, provide a total volume of 38 ml. However, in other embodiments, the mixing chamber may be any desired size.

[0233] Figure 38B is a bottom view of the top plate 1100. The fluid channels are shown in this view. These channels correspond to the channels in the mid-plate 1200 shown in Figures 39A-39B. The tops of the top plate 1100 and mid-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. Therefore, most of the fluid flow paths are in the top plate 1100 and mid-plate 1200. Figure 39B shows the first fluid inlet 810 and first fluid outlet 824.

[0234] In Figures 38A and 38B, the pod pumps 820, 828 include grooves 1002 (which in alternative embodiments are channels). The illustrated grooves 1002 have a predetermined size and shape, but in alternative embodiments, the size and shape of the grooves 1002 can be any suitable size and shape. Figures 38A and 38B show the size and shape of one embodiment. In all embodiments, the grooves 1002 form passages on the fluid inlet and fluid outlet sides of the pod pumps 820, 828. In alternative embodiments, the grooves 1002 are channels in the walls of the internal pump chambers of the pod pumps.

[0235] The grooves 1002 create a flow path so that even when the septum is at end-stroke, a flow path is still located between the inlet and outlet so that pockets of fluid or air are not trapped in the pod pump. The grooves 1002 are included on both the liquid or fluid side and the air or drive side of the pod pumps 820, 828. In some embodiments, the grooves 1002 are also included in the mixing chamber 818 (see Figures 40A and 40B for the air or drive side of the pod pumps 820, 828 and the opposite side of the mixing chamber 818). In alternative embodiments, the grooves 1002 are included on only one side of the pod pumps 820, 828, or not included at all.

[0236] In an alternative embodiment of the cassette, the liquid or fluid side of the pod pumps 820, 828 includes a feature (not shown) in which the inlet and outlet flow paths are continuous and a rigid outer ring (not shown) is molded around the pump chamber, which is also continuous. This feature maintains the seal formed with the septum (not shown). Figure 38E is a side view of the top plate 1100 of this embodiment.

[0237] Figures 39A and 39B show an embodiment of the midplate 1200. The midplate 1200 is further shown in Figures 37A-37F, which correspond to Figures 39A-39B. Accordingly, Figures 37A-37F show the location of the various valves and valve passages. The location of the diaphragms (not shown) for each pod pump 820, 828 as well as the location of the mixing chamber 818 are also shown.

[0238] FIG. 39A shows an embodiment of a cassette in which sensor elements are incorporated into the cassette to detect various properties of the pumped fluid. 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, the three sensor elements in two sensor cells 1314, 1316 are housed in sensor element housings 1308, 1310, 1312 and 1318, 1320, 1322, respectively. In one embodiment, two sensor element housings 1308, 1312 and 1318, 1320 house conductivity sensor elements, and the third sensor element housing 1310, 1322 houses a temperature sensor element. The conductivity sensor element and temperature sensor element may be any conductivity or temperature sensor element known in the art. In one embodiment, the conductivity sensor is a graphite post. In another embodiment, the conductivity sensor element is formed from stainless steel, titanium, platinum, or other metals that are coated for corrosion protection but still have electrical conductivity. The conductivity sensor element may include electrical wires 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, in an alternative embodiment, a combination of temperature and conductivity sensor elements similar to those disclosed in U.S. patent application Ser. No. DEKA-024XX, filed Oct. 12, 2007, and entitled "Sensor Apparatus System, Apparatus, and Method" is used.

[0239] In alternative embodiments, no sensors on the cassette are used, only one temperature sensor is used, only one or more conductivity sensors are used, or one or more other types of sensors are used.

[0240] FIG. 39C is a side view of the mid-plate 1200 in this embodiment. FIGS. 40A and 40B show the bottom plate 1300. FIG. 40A shows the inner or internal surface of the bottom plate 1300. The inner or internal surface is the surface that contacts the bottom surface of the mid-plate (not shown). The bottom plate 1300 is attached to air or drive lines (not shown). Shown are corresponding inlet holes for air to drive the pod pumps 820, 828 and valves (not shown here, see FIGS. 37A-37F) in the mid-plate 1300. Holes 810, 824 correspond to the first fluid inlet 810 and first fluid outlet 824, respectively, shown in FIG. 39B. Shown are channels 1002 for the pod pumps 820, 828 and the other flow paths of the corresponding halves of the mixing chamber 818. Pump drive holes are also shown. Unlike the top plate, the corresponding bottom plate 1300 halves of the pod pumps 820, 828 and mixing chamber 818 clarify the distinction between the pod pumps 820, 828 and mixing chamber 818. The pod pumps 820, 828 contain air or drive channels in the bottom plate 1300, while the mixing chamber 818 has an identical structure to its top plate half. The mixing chamber 818 does not contain both a septum (not shown) and an air or drive channel for mixing the liquids. Also shown are sensor cells 1314, 1316, which include three sensor element housings 1308, 1310, 1312 and 1318, 1320, 1322.

[0241] Figure 40B shows drive ports 1306 on the outer bottom plate 1300, or on the outside of the bottom plate 1300. A drive source is connected to these drive ports 1306. The mixing chamber 818 does not have a drive port because it is not air driven. Figure 40C is a side view of the bottom plate 1300 in an embodiment.

[0242] As noted above, in various embodiments of the invention, one or more fluid circuits, such as a blood flow circuit, a balancing circuit, a directing circuit, and / or a mixing circuit, are provided in a cassette. Other cassettes, such as sensing cassettes, are disclosed in U.S. Patent Application Serial No. 12 / 038,474, entitled "Sensor Instrumentation System, Apparatus, and Method," Docket No. F63, which is incorporated herein by reference in its entirety. In some embodiments, some or all of these circuits are combined in a single cassette. In alternative embodiments, these circuits are formed individually in each cassette. In yet other embodiments, two or more fluid circuits are included in a single cassette. In some embodiments, two, three, or more cassettes are immobile relative to one another, optionally communicating with one another. For example, in one embodiment, two cassettes are coupled by a pump, such as the pod pump described above. The pod pump includes rigid chambers with a flexible partition separating each chamber into a first side and a second side, each side serving a different purpose as described above.

[0243] Examples of cassettes that may be used in the present invention are those disclosed in U.S. patent application Ser. No. 11 / 871,680, filed Oct. 12, 2007, entitled "Pump Cassette," U.S. patent application Ser. No. 11 / 871,712, filed Oct. 12, 2007, entitled "Pump Cassette," and U.S. patent application Ser. No. 11 / 871,787, filed Oct. 12, 2007, entitled "Pump Cassette." No. 11 / 871,793, filed October 12, 2007, entitled "Pump Cassette," U.S. patent application Ser. No. 11 / 871,803, filed October 12, 2007, entitled "Cassette System Integrated Apparatus," and U.S. patent application Ser. No. F62, filed October 12, 2007, entitled "Cassette System Integrated Apparatus," each of which is incorporated herein in its entirety.

[0244] The cassette may further include various features such as pod pumps, fluid lines, valves, etc. The cassettes in the embodiments disclosed herein include various alternative embodiments. However, cassettes incorporating similar functionality are contemplated. While the cassettes in the embodiments disclosed herein are implementations of the fluid designs shown, alternative cassettes incorporating various fluid flow paths and / or valve arrangements and / or pod pump arrangements and numbers are within the scope of the present invention.

[0245] In one embodiment, the cassette includes a top plate, a midplate, and a bottom plate. There are various embodiments for each plate. Typically, the top plate contains the pump chambers and fluid lines, the midplate contains the complementary fluid lines, metering pumps and valves, and the bottom plate contains the actuation chambers (and in embodiments, the top and bottom plates contain complementary portions of balance chambers or pod pumps).

[0246] Typically, the bulkhead is located between the midplate and the bottom plate, but for balance chambers and pod pumps, a portion of the bulkhead is located between the midplate and the top plate. In some embodiments, the bulkhead is attached to the cassette by overmolding, capturing, gluing, press-fitting, welding, or any other process or method, but in some embodiments, the bulkhead is separate from the top, mid, and bottom plates until the plates are assembled.

[0247] The cassettes may be constructed from a variety of materials. Typically, in various embodiments, the materials used are solid and non-flexible. In one embodiment, the plates are made from polysulfone, while in other embodiments the cassettes may be made from other solid materials. In some embodiments, the plates are made from thermoplastic or thermosetting materials.

[0248] In one embodiment, the cassette is formed by placing bulkheads in precise locations (e.g., for one or more pod pumps, if present), assembling the plates in order, and connecting the plates. In one embodiment, the plates are connected using laser welding techniques. However, in other embodiments, the plates are glued, mechanically fastened, strapped together, ultrasonically welded, or connected using other methods of connecting plates.

[0249] In embodiments, the cassette is used to pump various types of fluids from a source to a location, including nutritive and non-nutritive fluids, inorganic chemicals, organic chemicals, bodily fluids, or any other type of fluid. Additionally, in embodiments, fluids include gases, and thus, in embodiments, the cassette is used to pump gases.

[0250] The cassette functions to pump and direct fluid from a preferred location to a preferred location. However, in some embodiments, the outer pump pumps fluid into the cassette and the cassette pumps fluid out. However, in some embodiments, the pod pump functions to draw fluid into the cassette and pump fluid out of the cassette.

[0251] As described above, the flow paths are controlled by the position of the valves. Accordingly, valves may be provided in different locations, or in other embodiments, additional valves may be provided in the cassette. Additionally, the illustrated fluid lines and flow paths described above are only examples of fluid lines and flow paths. In other embodiments, more, fewer, and / or different flow paths may be provided. In yet other embodiments, no valves are provided in the cassette.

[0252] The number of pod pumps (if present in the cassette) described above varies depending on the embodiment. For example, while various embodiments described above include two pod pumps, in other embodiments, the cassette includes one pod pump. In further embodiments, the cassette includes two or more pod pumps, or no pod pumps. The pod pump may be a single pump or multiple pod pumps ganged together to form a continuous flow. Either or both cassettes may be used in various embodiments. However, as described above, in some embodiments, no pod pumps are present in the cassette, or pod pumps are included between two or more cassettes. Examples of such systems are disclosed, but are not limited to, in U.S. patent application Ser. No. F62, entitled "Cassette System Integration Apparatus," which is incorporated herein by reference in its entirety.

[0253] The various fluid inlets and fluid outlets disclosed herein are fluid ports in some embodiments. Depending on the configuration and control of the valves in an implementation, a fluid inlet may be a fluid outlet. Therefore, referring to a fluid port as a fluid inlet or a fluid outlet is for descriptive purposes only. In various embodiments, interchangeable fluid ports are provided. Fluid ports are provided to impart specific flow paths to the cassette. These fluid ports need not all be used all the time. Instead, the use of various fluid ports allows for flexibility in the use of the cassette in implementation.

[0254] FIG. 46 illustrates an alternative, non-limiting example of a cassette. FIG. 46A illustrates an integrally formed, assembled cassette system. Mixing cassette 500, middle cassette 600, and balancing cassette 700 are connected by fluid lines or conduits. Pods are provided between the cassettes. FIGS. 46B and 46C illustrate the effectiveness of the integrated cassette system in various views. FIGS. 50A, 50B, and 50C illustrate fluid lines or conduits 1200, 1300, and 1400, respectively. Fluid flows between the cassettes through these fluid lines or conduits. FIGS. 50A and 50B illustrate that the larger fluid line or conduit 1300 and the smaller fluid line or conduit 1200 are check valves. In the illustrated embodiment, the check valves are duck-hand valves, but any check valves may be used in other embodiments. 50C illustrates that fluid line or conduit 1400 is a fluid line or conduit that does not include a check valve. For purposes of description, the terms "fluid line" and "conduit" are used interchangeably with respect to 1200, 1300, and 1400.

[0255] Figures 46B and 46C, as well as Figure 51A, illustrate the fluid flow through the various cassettes in one embodiment. For ease of description, the fluid flow begins with mixing cassette 500. Figures 46B and 51A illustrate the fluid side of mixing cassette 500. The fluid side includes multiple ports 8000, 8002, 8004, 8006, 8008, and 8010-8026, which are either fluid inlets or fluid outlets. In various embodiments, the one or more fluid inlets and outlets include one or more fluid inlets for reverse osmosis ("RO") water 8004, bicarbonate, acid, and dialysate 8006. Additionally, the one or more fluid outlets, including drains, include at least one vent outlet, as well as an outlet for acid 8002 and a dialysate tank. In one embodiment, tubing (not shown) is provided behind the outlets and is the outlet (to prevent contamination). Additional outlets are also included for water, bicarbonate and water mixture, and dialysate mixture (bicarbonate with added acid and water).

[0256] The dialysate then flows from the mixing cassette 500 to the dialysate tank (not shown here, shown in FIG. 51A as 1502), through conduits, and into the dialysate cassette 700 (outer dialysate cassette 600, pumped by pod pumps 602 and 604 (604 not shown here, shown in FIGS. 46D and 46E). The flow paths within the cassette vary; therefore, the locations of the various inlets and outlets vary with the various cassette flow paths.

[0257] Figure 51B shows one embodiment of a cassette system in which the condenser cell, conductivity sensor, and temperature sensor are contained in a separate cassette 1504 outside the cassette system shown in Figures 46A-46C. This outer sensor cassette 1504 is disclosed in U.S. patent application Ser. No. 12 / 038,474, Docket No. F63, entitled "Sensor Instrumentation Systems, Apparatus, and Methods," which is incorporated herein in its entirety.

[0258] Figure 51B shows the fluid flow path for this embodiment. During the mixing process for the dialysate in this embodiment, the bicarbonate mixture leaves the mixing cassette 500, flows to the outer sensor cassette, and then back to the mixing cassette 500. When the bicarbonate mixture reaches a predetermined threshold, acid is added to the bicarbonate mixture. The bicarbonate and acid are then mixed in the mixing chamber 506, and the dialysate flows from the cassette to the sensor cassette and back to the mixing cassette 500. This method and its control to ensure acceptable dialysate quality is formed and maintained throughout treatment are described in more detail below.

[0259] FIG. 46D shows that mixing cassette 500 includes a pneumatic drive. In the area designated by reference numeral 500, multiple valves and two pump chambers 8030, 8032 are provided in cassette 500 to pump or meter the acid and bicarbonate. In some embodiments, additional or fewer metering pumps are included. Metering pumps 8030, 8032 can be any size desired. 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 is advantageous and effective when using high concentrations of acid. This is because it is desirable to use smaller pumps for precision and so that full strokes, rather than partial strokes, can be used for control.

[0260] Conduits 1200, 1300 include check valves. These conduits 1200, 1300 allow for one-way flow. In some embodiments, these conduits 1200, 1300 are all directed to drain. The location of these check valve conduits is clear from the flow path schematic in FIG. 51A. In the illustrated embodiment, fluid directed to drain passes through the mixing cassette 500. FIG. 46B shows that a fluid drain port 8006 is provided on the fluid side of the cassette 500.

[0261] After the dialysate is mixed and flows through the sensor cassette, shown at 1504 in FIG. 51B, it is determined whether the dialysate is within predetermined parameters or thresholds, and then the dialysate is pumped back to the mixing cassette 500, passes through the flat conduit 1400, is sent to the outer dialysate cassette 600, passes through the mixing cassette 500 through the check valve conduit 1200, and travels to the drain fluid outlet.

[0262] 46D and 46E show various pods 502, 504, 506, 602, 604, 702, 704, 706, 708. Each of the pod housings is constructed similarly, but the interior of the pod housing differs depending on whether the pod is a pod pump 502, 506, 602, 604, 702, 704, a balance chamber pod 706, 708, or a mixing chamber pod 504.

[0263] Figures 46D and 46E, along with Figures 51A and 51B, illustrate the various pods provided in both the fluid flow path and the cassette system. Pod 502 is a water pod pump, and 504 is a bicarbonate-water pod pump (which pumps water to bicarbonate) for mixing cassette 500. Pod 506 is a mixing chamber. Once the dialysate is mixed in mixing chamber 506, it flows from mixing cassette 500 to sensor cassette 1504, which determines whether the dialysate is acceptable, and the dialysate flows through the mixing cassette dialysate tank outlet to dialysate tank 1502. However, if the dialysate is determined to be unacceptable, the fluid is returned to fluid cassette 500 and pumped through conduit 1400 to outer dialysate cassette 600, through check valve conduit 1200, past mixing cassette 500, and out the drain outlet.

[0264] Figures 46A-46C, along with Figures 51A and 51B, show the outer dialysate cassette 600 between the mixing cassette 500 and the inner dialysate cassette 700. Pod pumps 602, 604 pump dialysate from the dialysate tank 1502 and into the balance chambers 706, 708 of the inner dialysate cassette 700 (the motive force of the dialysate). The outer dialysate cassette 600 pushes dialysate into the inner dialysate cassette (i.e., the pump of the inner dialysate cassette 700 does not pump dialysate). Thus, dialysate from the outer dialysate cassette 600 is pumped from the dialysate tank 1502 through the heater 1506, through the ultrafiltration membrane 1508, and into the inner dialysate cassette 700.

[0265] 51A and 51B, as well as FIGS. 46D and 46E, illustrate that the inner dialysate cassette 700 includes a metering pod 8038 (i.e., an ultrafiltration metering pod), balancing pods 706, 708, and pod pumps 702, 704. The inner dialysate cassette 700 also includes fluid outlets and fluid inlets. These inlets and outlets include an outlet to the dialyzer 1510, an inlet from the dialyzer 1510, and a dialysate inlet (the ultrafiltration membrane 1508 connects to a port on the inner dialysate cassette). Fluid inlets and outlets are also included for DCA and DCV connections during priming and disinfection. Various conduits (1200, 1300, 1400) function to allow fluid communication between the cassettes 500, 600, and 700 and to allow fluid flow through the mixing cassette 500 to drain. The largest check valve 1300 (also shown in Figure 50B) is used during disinfection. This tubing is oversized to accommodate blood clots and other contaminants that flow through the tubing during disinfection in the preferred embodiment.

[0266] In some embodiments, the valves and pumps of the cassette system are pneumatically actuated. A separate pneumatic source is attached to the cassette via a separate tube. Thus, each pump, balancing pod, or valve is individually connected to a pneumatic actuation manifold (not shown). Figures 52A-52F show an embodiment in which the tubes are connected to at least one block 1600. In some embodiments, multiple blocks are used to connect the various tubes. Block 1600 is dropped into the manifold and then suitably connected to a pneumatic actuator. This allows the pneumatic tubes to be easily connected to the manifold.

[0267] 46D further illustrates that in one embodiment, the cassette system includes a spring 8034 to assist in holding the system together. The spring 8034 is attached to the mixing cassette 500 and the inner dialysate cassette 700 by a grasper 8036. However, in other embodiments, other means or devices may be used to assist in maintaining the proper system in a preferred orientation, including, but not limited to, latching means, resilient means, etc.

[0268] 47A-47C show an example pod. The pod includes two fluid ports 902, 904 (inlet and outlet), and the pod may be assembled differently in various embodiments. Various embodiments of the structure are disclosed, but not limited to, in U.S. patent application Ser. No. 11 / 787,212, Docket No. E78, filed Apr. 13, 2007, and entitled "Fluid Pumping System, Apparatus, and Method," which is incorporated herein by reference in its entirety.

[0269] Figures 47A, 47D, and 47E show chamber grooves 906. Grooves 906 are included in each half of the pod housing. In other embodiments, grooves are not included, and in some embodiments, grooves are included in only one half of the pod.

[0270] Figures 48A and 48B show an embodiment of a membrane used in pod pumps 502, 504, 602, 604, 702, and 704. This membrane is described above in Figure 5A. In another embodiment, the membrane shown in Figures 5B-5D is used. Figure 49 is an exploded view of an embodiment of a pod pump.

[0271] In various embodiments of the invention, one or more "pod pumps" are used for various purposes. The structure of the pod pump is described above and below. This structure can be modified for various uses, such as a pump, balancing chamber, mixing chamber, etc. Additionally, the pod pump can be located anywhere in the system, such as in a cassette or between two or more cassettes.

[0272] Typically, a pod pump includes rigid chambers (e.g., having a suitable shape, such as a spherical shape, an ellipsoidal shape, etc.), and the pod pump includes a flexible partition dividing each chamber into a first half and a second half. In some embodiments, the rigid chambers are spheroids. As used herein, the term "spheroid" refers to a three-dimensional shape corresponding to an ellipse rotated about one of its major, major, or minor axes, and generally includes three-dimensional ovals, oblate and prolate spheroids, spheres, and similar shapes.

[0273] Each half of the pod pump has at least one inlet valve and usually (but not necessarily) at least one outlet valve (in some embodiments, the same port is used for both the inlet and outlet). For example, the valves may be on-off valves or two-way proportional valves. For example, the valves on one side of the chamber may be two-way proportional valves, one connected to a high-pressure source and the other to a low-pressure (or vacuum) sink. The valves on the other half may be opened or closed to direct the fluid.

[0274] In some embodiments, the septum has a varying cross-sectional thickness. Thinner, thicker, or variable thickness septums may be used to accommodate the stiffness, flexibility, and other properties of the selected septum material. The thickness of the thin, thick, or variable septum wall may be used to control the septum, promoting flexure in certain areas relative to other areas, thereby aiding in pumping action and controlling the flow of the primary fluid through the pump chamber. In this embodiment, the septum is shown with the thickest cross-sectional area closest to the center. However, in other embodiments, septums with varying cross-sections may be provided, with the thickest and thinnest areas located anywhere on the septum. Thus, for example, thinner cross-sections may be located near the center and thicker cross-sections may be located near the periphery of the septum. In one embodiment, the septum has at least one tangential slope; in other embodiments, the septum is completely smooth or substantially smooth.

[0275] The septum is made of a flexible material that has desirable durability and is compatible with fluids. The septum is formed from a material that flexes in response to fluid, liquid, or gas pressure or vacuum acting on the actuation chamber. The septum material is further selected for biocompatibility, temperature compatibility, and compatibility with the various primary fluids that may be pumped by the septum or introduced into the chamber, facilitating septum movement. In one embodiment, the septum is formed from high-stretch silicone. However, in other embodiments, the septum may be made from elastomers or rubbers, including, but not limited to, silicone, urethane, nitrile, EPDM, or other rubbery, elastomeric, or flexible materials.

[0276] The shape of the septum is dependent on a variety of factors, including, but not limited to, the shape of the chamber, the dimensions of the chamber, the characteristics of the primary fluid, the volume of the primary fluid pumped per stroke, and the means and mode of attachment of the septum to the housing. The dimensions of the septum are dependent on a variety of factors, including, but not limited to, the shape of the chamber, the dimensions of the chamber, the characteristics of the primary fluid, the volume of the primary fluid pumped per stroke, and the means and mode of attachment of the septum to the housing. Thus, the shape and dimensions of the septum will vary in various embodiments depending on these and other factors.

[0277] The septum can be any thickness. However, in embodiments, the thickness ranges between 0.002 inches and 0.125 inches (approximately 0.00508 cm and 0.3175 cm) (1 inch = 2.54 cm). The preferred thickness varies depending on the material used for the septum. In one embodiment, high elongation silicone is used at a thickness of 0.015 inches to 0.050 inches (approximately 0.0381 cm to 0.127 cm). However, in other embodiments, the thickness may vary.

[0278] In some embodiments, the septum is preformed to include a generally dome-shaped configuration over at least a portion of the area of ​​the septum. Further, the dimensions of the dome may vary based on some or many of the factors discussed above. However, in other embodiments, the septum does not include a preformed dome-shaped configuration.

[0279] In some embodiments, the dome of the septum is formed using fluid injection molding. However, in other embodiments, the dome can be formed using compression molding. In alternative embodiments, the septum is generally flat. In other embodiments, the dimensions, width, or height of the dome vary.

[0280] In various embodiments, the septum is retained by various means and methods. In one embodiment, the septum is clamped between portions of the cassette. In some embodiments, the edges of the cassette include features that grip the septum. In other embodiments, the septum is clamped to the cassette using at least one bolt or other device. In other embodiments, the septum is overmolded with a plastic portion, and the plastic is welded or glued to the cassette. In other embodiments, the septum is sandwiched between a midplate and a bottom plate. While embodiments disclose attachment of the septum to the cassette, other methods and means for attaching the septum to the cassette may be used. In alternative embodiments, the septum is directly attached to a portion of the cassette. In some embodiments, the septum has a thicker edge compared to other regions, and the septum is sandwiched by plates. In some embodiments, this thicker region is a gasket, in some embodiments an O-ring, ring, or other shaped gasket.

[0281] In some embodiments, the gasket is continuous with the bulkhead. However, in other embodiments, the gasket is a separate part from the bulkhead. In some embodiments, the gasket is formed from the same material as the bulkhead. However, in other embodiments, the gasket is formed from a separate material from the bulkhead. In some embodiments, the gasket is formed by overmolding a ring around the bulkhead. The gasket can be any shape ring or suitable seal to complement the pod pump housing in some embodiments. In some embodiments, the gasket is a compression-type gasket.

[0282] Due to the rigid chambers, pod pumps typically have a fixed volume. However, within a pod pump, the first and second compartments have different volumes due to the location of a flexible partition separating the chambers. Forcing fluid into one compartment displaces fluid in the other compartment of the chamber. However, the fluids do not directly contact each other within the pod pump due to the typically flexible partition.

[0283] Thus, in one embodiment, a pod pump used for pumping is configured to receive a control fluid in a first compartment and a fluid to be pumped in a second compartment. The control fluid may be a fluid, i.e., a liquid or a gas. In one embodiment, the control fluid is air. By evacuating the control fluid from the pod pump (e.g., by vacuum or at least a pressure lower than the pressure within the pod pump), the pod pump draws fluid (e.g., blood, dialysate, etc.) into the other compartment of the pod pump. Similarly, by forcing control fluid into the pod pump (e.g., from a high-pressure source), the pod pump evacuates the fluid. Further, by controlling the valve in the second compartment, the fluid is transported through the first valve and expelled through the second valve by the action of the control fluid.

[0284] Alternatively, pod pumps may be used to balance fluids, such as dialysate, as described above. In such cases, instead of a control fluid, fluid is directed to each compartment of the pod pump. As described above, the volume of a pod pump is typically fixed by a rigid chamber. Thus, when a first volume of fluid is pumped into a first compartment of the balancing pod, an equal volume of fluid is expelled from a second compartment of the balancing pod (assuming that the fluid is typically incompressible under pod actuation conditions). Thus, equal volumes of fluid can be moved using the balancing pod. For example, in FIG. 5, the balancing pod allows fresh dialysate to enter the first compartment and spent dialysate to enter the second compartment. The flows of fresh and spent dialysate volumes are balanced with each other.

[0285] In some embodiments, a pod pump is used that does not include a flexible dividing wall between chambers. In such examples, the pod pump can be used as a mixing chamber. For example, mixing chamber 189 in FIG. 7A is such a pod pump.

[0286] FIG. 9 shows a non-limiting example of a pod pump. This figure illustrates a cross-sectional view of a pneumatically controlled valve used in an embodiment of a cassette. As used herein, the term "pneumatic" refers to the use of air or other gas to move a flexible diaphragm or other member (the use of air is exemplary only; alternative examples include other control fluids such as nitrogen (N2), carbon dioxide, water, and oil). Three rigid portions are used: a "top" plate 91, a mid-plate 92, and a "bottom" plate (the terms "top" and "bottom" are used only to refer to the orientation shown in FIG. 9; the valve may be oriented in any direction in practice). The top and bottom plates 91 and 93 are flat on both sides, while the mid-plate 92 has channels, indentations, and holes to form various flow paths, chambers, and ports. A diaphragm 90 forms a valve chamber 97 along the mid-plate 92. Air pressure is applied through air port 96, with positive gas pressure forcing diaphragm 90 against valve seat 99 to close the valve, or negative gas pressure pulling the diaphragm away from the valve seat and opening the valve. A control gas chamber 98 is formed by diaphragm 90, top plate 91, and mid-plate 92. Mid-plate 92 includes an indentation into which diaphragm 90 rests, thereby forming control gas chamber 98 on one side of the diaphragm and valve chamber 97 on the opposite side.

[0287] Air ports 96 are formed by channels formed by the "top" surface of mid-plate 92 in conjunction with top plate 91. By providing communication between multiple valve chambers in the cassette, the valves are ganged so that all ganged valves are opened and closed simultaneously by a single source of air pressure. Channels formed in the "bottom" surface of mid-plate 92 in conjunction with the bottom plate form valve inlets 94 and valve outlets 95. Holes formed through mid-plate 92 provide communication between inlets 94 and valve chambers 97 (through valve seats 99) and between the valve chambers and outlets 95.

[0288] The septum 90 has a thickened edge 88 that fits tightly into a groove 89 in the midplate 92. The septum 90 is therefore positioned in and retained by the groove 88 prior to the top plate 91 being ultrasonically welded to the midplate 92. Therefore, the septum does not interfere with the ultrasonic welding of the two plates. The septum does not depend on the two plates being ultrasonically joined precisely in place. Therefore, the valve is easily manufactured without very tight ultrasonic welding. As shown in FIG. 9 , the top plate 91 includes additional material extending into the controlled gas chamber 98, which prevents the septum from moving too far away from the groove 89 and prevents the septum's thickened edge 88 from retracting from the groove 89.

[0289] A pressure sensor is used to monitor the pressure in the pod. For example, by alternately applying air pressure to the air side of the chamber, the diaphragm cycles back and forth across the total chamber volume. With each cycle, air pressure applies a vacuum to the pod, causing fluid to be pumped through a valve upstream of the inlet fluid port. Air pressure applies positive pressure to the pod, causing fluid to be expelled through the outlet port and downstream valve.

[0290] FIG. 10 is a cross-sectional view of an embodiment of a pod pump incorporated into an embodiment of a fluid-control cassette. In the embodiment, the cassette incorporates multiple pod pumps and multiple valves formed by the construction techniques shown in FIGS. 9 and 10. In the above embodiment, the pod pump of FIG. 10 is formed from different portions of the same three rigid sections used to form the valve of FIG. 9. These rigid sections are a "top" plate 91, a mid-plate 92, and a "bottom" plate (as noted above, the terms "top" and "bottom" only refer to the orientation shown in FIG. 9). To form the pod pump, the top plate 91 and the bottom plate 93 include generally hemispherical portions that together form the hemispherical pod pump.

[0291] A diaphragm 109 separates the pod pump's central cavity into a chamber that receives the fluid to be pumped (the pump chamber) and another chamber that receives a control gas that pneumatically drives the pump (the drive chamber). An inlet 94 allows fluid to enter the pump chamber, and an outlet allows fluid to leave the pump chamber. The inlet 94 and outlet 95 are formed between the midplate 92 and the bottom plate 93. Air pressure is applied through air ports 106 to the diaphragm 109 against one wall of the pod pump cavity with positive gas pressure, minimizing the pump chamber volume, as shown in FIG. 10, or to the diaphragm against the other wall of the pod pump cavity with negative gas pressure, maximizing the pump chamber volume.

[0292] In some embodiments, the pod pump may utilize various structures, including grooves in one or more plates exposed to the pod pump cavity, which, among other things, may prevent the septum from blocking the inlet and / or outlet flow paths for fluid and / or air.

[0293] The septum 109 is formed with a thickened lip 88 that is firmly held in the groove 89 in the mid-plate 92. Thus, like the valve chamber of FIG. 9, the septum 109 is positioned in and held by the groove 89 prior to the top plate 91 being ultrasonically welded to the mid-plate 92. Thus, the septum does not interfere with the ultrasonic welding of the two plates. The septum is not dependent on the two plates being ultrasonically joined precisely in place. Therefore, this valve is easily manufactured without the need for very tight ultrasonic welding.

[0294] Figure 11A is a schematic diagram illustrating an embodiment of a pressure drive system 110 for a pod pump such as that shown in Figure 10. In this example, air is used as the control fluid (e.g., the pump is pneumatically driven). As noted above, in other embodiments, other fluids (e.g., water) are used as the control fluid.

[0295] 11A, pressure drive system 110 applies alternating positive and negative pressure to the gas in drive chamber 112 of pod pump 101. Air pressure drive system 110 includes drive chamber pressure transducer 114, variable positive supply valve 117, variable negative supply valve 118, positive pressure gas tank 121, negative pressure gas tank 122, positive pressure tank pressure transducer 115, negative pressure tank pressure transducer 116, as well as electronic controller 119.

[0296] The positive pressure tank 121 applies a positive pressure of control gas to the drive chamber 112, pushing and moving the partition 109 to a position where the pump chamber 111 has the minimum capacity (i.e., the position where the partition is against the solid wall of the pump chamber). The negative pressure tank 122 applies a negative pressure of control gas to the drive chamber 112, pushing and moving the partition 109 in the opposite direction to a position where the pump chamber 111 has the maximum capacity (i.e., the position where the partition is against the solid wall of the drive chamber).

[0297] In this example, a valve system is used to control communication between each of these tanks 121, 122 and the actuation chamber 112. In Figure 11A, separate valves are used for each tank. Positive supply valve 117 controls communication between the positive pressure tank 121 and the actuation chamber 112, and negative supply valve 118 controls communication between the negative pressure tank 122 and the actuation chamber 112. These two valves are controlled by an electronic controller 119 (alternatively, a single three-way valve is used in place of the two separate valves 117, 118). In an embodiment, the positive supply valve 117 and the negative supply valve 118 are variable restriction valves as opposed to two-way on-off valves. The advantages of using variable valves are discussed below.

[0298] 11A shows that the controller 119 also receives pressure information from three pressure transducers: the actuation chamber pressure transducer 114, the positive pressure reservoir pressure transducer 115, and the negative pressure reservoir pressure transducer 116. As the names suggest, these transducers measure the pressure in the actuation 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, 122 to ensure they are appropriately pressurized (positively or negatively). Compressor-type pumps or pumps are used to obtain the appropriate pressures in these reservoirs 121, 122.

[0299] In one embodiment, the pressure exerted by positive pressure reservoir 121 is strong enough to press septum 109 against the rigid pump chamber wall under normal conditions. Similarly, the negative pressure (i.e., vacuum) exerted by negative pressure reservoir 122 is strong enough to press the septum against the rigid drive chamber wall under normal conditions. However, in one embodiment, these positive and negative pressures provided by reservoirs 121, 122 are well within safe limits, which are the same pressures that would open either positive supply valve 117 or negative supply valve 118, and the positive and negative pressures exerted against septum 109 are not strong enough to cause harm to the patient.

[0300] In one embodiment, the controller 119 monitors pressure information from the actuation chamber pressure transducer 114 and, based on this information, controls the valve mechanism (valves 117, 118) to move the diaphragm 109 to a position of minimum pump chamber volume, and after reaching this position, pulls the diaphragm 109 to move it to a position of maximum pump chamber volume.

[0301] The pressure drive system (including drive chamber pressure transducer 114, positive pressure reservoir pressure transducer 115, negative pressure reservoir pressure transducer 116, variable positive supply valve 117, variable negative supply valve 118, controller 119, positive pressure gas reservoir 121, and negative pressure gas reservoir 122) is located entirely or substantially outside the isolated volume, designated by reference numeral 61 in Figure 6. In some embodiments, components that come into contact with the blood or dialysate (i.e., pod pump 101, inlet valve 105, and outlet valve 107) are located in the isolated volume so that they can be more easily disinfected.

[0302] FIG. 11B shows another example of a pressure actuation system 110 for a pod pump. In this example, pod pump 101 includes pump chamber 111, driver chamber 112, and a diaphragm 109 separating them into two sides. Fluid ports 102 and 104 allow access to fluid into and out of pump chamber 111 using fluid valves (not shown). However, within pod pump 101, fluid ports 102 and 104 include "volcano" ports 126, typically having a raised shape, so that when diaphragm 109 contacts the port, it tightly seals the port. FIG. 11B also shows a three-way valve connecting pressure tanks 121 and 122. Three-way valve 123 communicates with driver chamber 112 through one port in this example.

[0303] 11A and 11B show that instead of the two tank pneumatic drive system, other types of drive systems can be used to move the bulkhead back and forth.

[0304] As mentioned above, the positive supply valve 117 and the negative supply valve 118 of the air drive system 110 of FIG. 11A are preferably variable restriction valves rather than two-way on / off valves. The use of variable valves allows the pressure applied to the drive chamber 112 and diaphragm 109 to be easily controlled by a small amount of pressure in the reservoirs 121 and 122, instead of applying full reservoir pressure to the diaphragm. Therefore, the same reservoir or set of reservoirs can be used for different pod pumps, even if the pressures required to drive the pod pumps differ. While the reservoir pressure needs to be greater than the desired pressure applied to the various pod pump diaphragms, one pod pump may be driven by half reservoir pressure, while another pod pump, driven by the same reservoir but at one-quarter reservoir pressure, may be driven by a different reservoir. Therefore, even if different pods in a dialysis system are designed to operate at different pressures, these pod pumps may all share the same reservoir or set of reservoirs, but may be driven at different pressures using different valves. The pressure used in the pod pump varies in response to conditions that arise or change during the dialysis process. For example, if the tubing in the system becomes compressed due to tubing distortion, the positive and / or negative pressure used in the pod pump may increase to compensate for the increased restriction.

[0305] FIG. 12 is a graph illustrating how the pressure applied to the pod pump is controlled using a variable valve. The vertical axis indicates the pressure in the positive and negative reservoirs (121 and 122 in FIG. 11A), respectively, using PR+ and PR-. PC+ and PC- indicate the positive and negative control pressures acting on the pod pump's diaphragm, respectively. As shown in FIG. 12, from time T0 to approximately time T1, a positive pressure is applied to the actuation chamber (to force fluid out of the pump chamber). By repeatedly increasing and decreasing the flow restriction provided by the positive variable valve (117 in FIG. 11A), the pressure applied to the actuation chamber is maintained at approximately the desired positive control pressure PC+. The pressure varies in a sinusoidal pattern around the desired control pressure. A drive chamber pressure transducer (114 in FIG. 11A) in communication with the drive chamber measures the pressure in the drive chamber and transmits the pressure measurement to a controller (119 in FIG. 11A) that controls the variable valve so that the drive chamber pressure varies around the desired control pressure PC+. Absent a fault condition, the diaphragm presses against the solid wall of the pump chamber, thereby terminating the stroke. The controller determines that the end of stroke has been reached when the pressure measured in the drive chamber does not drop as the restriction created by the variable valve decreases. In FIG. 12, the end of the exhaust stroke occurs around time T1. Once the end of stroke is detected, the controller fully closes the variable valve to prevent the drive chamber pressure from increasing above the desired control pressure PC+.

[0306] After the positive variable valve closes, the negative variable valve (118 in FIG. 11A) partially opens, allowing the negative pressure reservoir to draw gas from the drive chamber and fluid into the pump chamber. As shown in FIG. 12, negative pressure is applied to the drive chamber from shortly after T1 until time T2. As with the exhaust (positive pressure) stroke, by repeatedly increasing and decreasing the flow restriction created by the variable valve, the pressure applied to the drive chamber can be maintained at approximately the desired negative control pressure PC- (less than the negative pressure reservoir pressure). The pressure varies in a sinusoidal pattern around the desired control pressure PC-. The drive chamber pressure transducer sends pressure measurement information to the controller, which controls the variable valve to vary the drive chamber pressure around the desired control pressure PC-. If no fault conditions exist, the diaphragm is pulled against the solid wall of the drive chamber, thereby completing the pull (negative pressure) stroke. As described above, the controller determines that the end of stroke has been reached when the partial vacuum measured in the drive chamber does not drop as the restriction created by the variable valve decreases. In Figure 12, the end of the draw stroke occurs around time T2. When the end of stroke is detected, the controller fully closes the variable valve to prevent the drive chamber vacuum from rising above the desired negative control pressure PC-. Once the draw stroke is complete, the positive variable valve partially opens, initiating a new exhaust stroke with positive pressure.

[0307] Thus, each pod pump in this example uses two variable aperture valves to throttle flow from a positive pressure source to a negative pressure. The pressure in the drive chamber is monitored, and the controller uses this pressure measurement to determine the appropriate command for both valves to achieve the desired drive chamber pressure. The advantages of this configuration are that fill and deliver pressures are precisely controlled to achieve the desired flow rate while respecting pressure limits, and that the pressure varies with a small sinusoidal signature command. This signature is monitored to determine when the pump is at the end of its stroke.

[0308] Another advantage of using a variable valve instead of a two-way valve as described above is that by only partially opening and closing the variable valve, wear on the valve is reduced. Repeated "hard" opening and closing of the two-way valve shortens the valve's lifespan.

[0309] The end of the stroke is detected and the integrated value of the correlation function is very small, indicating that the stroke was blocked and not completed. By identifying the fill stroke or the transfer stroke, downstream blockages can be distinguished from upstream blockages (which is difficult for blockages that occur near the end of the stroke when the septum is located close to the chamber wall). Figures 13A and 13B show the detection of a blockage (the chamber pressure drops to zero when a blockage is detected).

[0310] Under normal operation, the integrated value of the correlation function increases as the stroke progresses. If this value remains small or does not increase (in the case of very low impedance flow or blockages), the stroke is either too short or the actual pressure does not follow the desired sinusoidal pressure pattern due to a faulty valve or a faulty pressure signal. The lack of correlation is detected and used in error handling in these cases.

[0311] Under normal circumstances, when the flow controller is running, the control loop adjusts the pressure in response to changes in fluid velocity. If the circuit impedance increases dramatically and the pressure limit saturates before flow has a chance to reach the desired rate, the flow controller will not be able to adjust the pressure higher to reach the desired fluid velocity. These conditions occur when a blood clot forms in the circuit or when the line becomes partially occluded. These are used in error handling when pressure saturation is detected when flow does not reach the desired flow rate.

[0312] If there is a valve or air pressure problem, such as a leaking fluid valve or noise in the pressure signal, the ripple will continue unclearly on the stroke and the end-of-stroke algorithm will not see enough change in the pressure ripple to detect the end of the stroke. Therefore, a safety check is added to detect if the stroke is completed more quickly than necessary. This information can be used for error handling.

[0313] In a dual pump, such as pump 13 shown in FIG. 3A, the two pump chambers cycle in opposite directions, affecting the pump period. A phase relationship ranging from 0° (both chambers function in the same direction) to 180° (chambers function in opposite directions) is selectable. Because it is not possible to move both chambers in the same direction simultaneously, the phase movement can be varied in some embodiments. If they were to move simultaneously, both the inlet and outlet valves would open and the end of stroke would not be properly detected.

[0314] Selecting a 180° phase relationship results in continuous flow into and out of the pod. This is the nominal pump mode when continuous flow is desired. A 0° phase relationship setting is useful for single-needle flow. The pod is first filled with the needle and then delivered to the same needle. Driving at a phase between 0° and 180° can be used to achieve a tension relationship across the dialyzer (hemodiafiltration or continuous backflush). Figures 8A-8C graphically illustrate these phase relationships.

[0315] The pod pump controls the flow of fluid through various subsystems. For example, a sinusoidal pressure waveform is added to a DC pressure command to form the commanded pressure signal for the pod pump. When the diaphragm is moving, the pod pressure tracks the sinusoidal command. When the diaphragm contacts the chamber wall and stops moving, the pod pressure remains constant and does not track the sinusoidal input command. The difference in the pod's subsequent pressure signal commands is used to detect the end of the stroke. From the end-of-stroke information, the time of each stroke is calculated. By knowing the pod's volume and when it completes a stroke, the flow rate for each pod is determined. The flow rate is fed back into a PI loop to calculate the required DC pressure for the next stroke.

[0316] The magnitude of the sinusoidal input is selected to be large enough relative to the actual pressure to adequately track the command, and small enough so that when subtracted from the DC pump pressure and applied to the pod, the pressure is sufficient to move the diaphragm under the expected operating conditions of fluid viscosity, head height, and circuit resistance. The frequency of the sinusoidal input is empirically selected to ensure reliable end-of-stroke detection. The more periods of the sine wave per stroke, the more accurate the end-of-stroke detection algorithm will be.

[0317] At the end of a pump stroke or during a blockage in the pod pump's outlet line, the measured pressure deviates from the expected pressure. In one embodiment, to detect deviations in the pod pump's measured pressure from the demanded pressure, the commanded pressure signal and the measured pressure signal in the pod may be sent through a cross-correlation filter. Preferably, the size of the sampling window for the cross-correlation filter is equal to the period of the input sine wave. For every sample in the window, the demanded pressure signal is multiplied by the previous sample of actual pressure and added to the previous correlation value. The window is then shifted by one frame, and the process is repeated. In one embodiment, the resulting product is then separated and passed through a second-order filter with a corner frequency equal to the frequency of the input sine wave and a damping ratio of 1. The effect of this filter is to act as a bandpass filter, isolating signals that are correlated at the frequency of the input sine wave. Optionally, the absolute value of the output of this filter may then be passed through a second-order low-pass filter with the same frequency as the sine wave frequency and a damping ratio of, for example, about 3.0. This second filter is used to integrate the differentiated signal with the resulting signal and reduce noise in the resulting signal. When the two signals are correlated, the resulting filtered value is large. When the two signals are uncorrelated (e.g., at the end of the stroke), the resulting filtered value is small. The end of the stroke can be detected when the filtered cross-correlated signal falls below a predetermined threshold or when the signal drops by a percentage of its maximum value over the stroke. This threshold or percentage drop can be varied as a function of pressure or flow rate to tune performance for specific pump scenarios.

[0318] To detect the end of stroke, the end-of-stroke algorithm typically takes approximately one period of the sine ripple, so minimizing this period (maximizing the sine wave frequency) reduces the delay at the end of stroke. Low-pressure, high-frequency flows are not tracked well by the controller. Because flow velocity tends to decrease as stroke pressure decreases, the end-of-stroke delay is a lower percentage of the total stroke time. Therefore, the frequency can be lower for low-pressure strokes. The frequency of the sine wave can be adjusted as a linear or other function of the delivery pressure. This ensures minimal delay when strokes are short. As the frequency of the sine wave at the desired pressure changes, the filter for the cross-correlation function must also be adjusted. The filter is configured to continuously calculate filter coefficients based on this changing frequency.

[0319] The pressure in the pod chamber may be controlled using two variable solenoid valves, one connecting the plenum to a higher pressure source and the other connecting the plenum to a lower pressure (or vacuum) sink. Solenoid valves tend to have large neutral zones, so a non-linear offset term may be added to the controller's algorithm to compensate. Phase-insensitive cross-correlation The system controller 119 (FIG. 11A) can analyze the pressure response to changes in flow restriction in the valves 117, 118 (e.g., variable valves) that operate the pressure-driven reciprocating pump 110 in several ways. One technique uses a cross-correlation filter that is insensitive to phase shifts in the pressure signal in the pump's drive chamber 112 compared to the signals that control the operation of the valves. Applying the phase-insensitive cross-correlation filter to the pressure and valve signal data generates a set of values ​​referred to herein as correlation coefficients. The correlation coefficients are a quantitative measure of the correlation between the pressure measured in the drive chamber 112 and the periodically changing signals that operate the opening or closing of either the variable valve 117, which supplies positive pressure to the pump drive chamber, or the variable valve 118, which supplies negative pressure to the pump drive chamber.

[0320] In one embodiment, the signal operating the variable valves 117, 118 to achieve the desired pressure in the actuation chamber 112 may be the output of a closed-loop controller that varies the valve command signal. In this embodiment, the desired pressure is varied periodically, and the controller varies the valve command signal to minimize the difference between the desired pressure and the measured pressure at each time increment. In this embodiment, a correlation coefficient may be calculated between the desired pressure to drive the valve controller and the measured pressure in the actuation chamber.

[0321] In one example, the correlation coefficient number may be used to provide estimates of the instantaneous flow rate of the pumped fluid as well as several other conditions, including end-of-stroke, partial occlusion, and total occlusion. The correlation coefficient number may be calculated using several inputs, including, but not limited to, the pressure signal received from the pump pressure sensor 114, the amplitude of the electronic signal operating the valves 117, 118 (variable valves in this example), and the frequency of the time-varying signal (e.g., ripple waveform) sent to the valve operating signal. In this example, the correlation coefficient number may be used to describe various operating parameters of the pod pump in the hemodialysis machine 6001 (represented in block form in FIG. 61 ). The correlation coefficient number may also be used in other systems in which fluid is pumped into or out of a pressure-driven reciprocating pump that includes a control or drive chamber that is exposed to positive or negative fluid pressure (e.g., air pressure, etc.) by operation of a variable valve fluidly connected to a positive and / or negative pressure source.

[0322] In one aspect, the correlation coefficient may be considered to be the vector sum of a cross-correlation of the time-varying command signal to the supply valve with the response pump pressure signal and a second cross-correlation of the displayed command signal with the constant pressure signal. This arithmetic operation results in a correlation coefficient that may be insensitive to the phase angle between the variable valve signal and the signal related to pressure changes in the pump drive chamber. In one embodiment, the cross-correlation is calculated for the pressure signal and a valve command signal that is delayed or shifted by one-quarter of the period of the input sine wave.

[0323] The principle underlying the calculation of the correlation coefficient is shown in FIG. 130. In this example, a variable valve is used to provide positive or negative air pressure to a pressure-driven reciprocating pump. The size of the sampling window 12010 for the cross-correlation filter is equal to the period of the variable valve signal 12020. The variable valve signal is preferably a DC signal with a sinusoidal waveform superimposed. In alternative embodiments, other time-varying periodic signals, such as a triangular or square wave, may be applied to the DC signal. The controller can calculate the cross-correlation between the variable valve command signal and the pressure signal by digitally sampling the variable valve command signal and the pump pressure signal and multiplying the AC component of the variable valve signal with the AC component of the measured pressure signal at each sample point in the sampling window. The product of the two AC signals is then summed at each sample point in the sampling window.

[0324] A second cross-correlation is calculated from the pressure AC signal and a variable valve command signal that is shifted in time by a quarter cycle or 90 degrees. This second cross-correlation is calculated by multiplying the AC component of the measured pressure signal by the AC component of the shifted variable valve signal at each sample point in the sampling window. The products of the two AC signals are then summed at each sample point in the sampling window.

[0325] The magnitude of the vector sum of these two cross-correlations is then calculated by taking the square root of the sum of the squares of the first cross-correlation and the second cross-correlation to obtain a correlation coefficient. One benefit of taking the vector sum of the first cross-correlation and the quarter-period shifted second cross-correlation includes reducing the sensitivity of the correlation coefficient to changes in phase between the pressure signal and the variable valve signal. Finally, to reduce noise, the pressure signal may be passed through a second-order filter with a cutoff frequency that may be equal to the frequency of the variable valve signal, for example.

[0326] A correlation angle can be calculated from the first and second cross correlations by considering the first cross correlation as a horizontal vector and the second cross correlation as a vertical vector. The correlation angle is the angle between the vector sum and the first cross correlation. This angle can be considered a measure of the phase shift of the actuation chamber pressure relative to the valve actuation signal.

[0327] The controller may be programmed in several ways to calculate the correlation coefficients. For example, the AC component of each signal may be calculated by subtracting the signal's average value from the sampled values. The variable valve signal and pressure signal may be averaged over the first few samples before the cross-correlation calculation begins. This method helps reduce the effects of noise in the pressure signal. In a preferred embodiment, the AC components of the variable valve signal and pressure signal are calculated by taking the derivative of the variable valve signal and pressure signal with respect to time. The derivative calculation is relatively flexible and robust. One implementation of this calculation to determine the first cross-correlation (A) for discrete sample points of the variable valve signal and pressure signal is shown in Equation 1 below.

[0328]

number

[0329] The same calculation can be repeated to calculate a second cross correlation with the variable valve signal shifted by a quarter period, as shown in Equation 2 below.

[0330]

number

[0331] As shown in Equation 3 below, the raw correlation coefficient number can be defined as the square root of the sum of the squares of the first cross-correlation value A and the second cross-correlation value B.

[0332]

number

[0333] Corr(i):=Raw(i-1)+α·(Raw(i)-Corr(i-1)) formula 4 where α is a smoothing coefficient with 0<α<1.

[0334] The correlation angle may be calculated from the first cross correlation value and the second cross correlation value as follows:

[0335]

number

[0336] Graphs of the first cross correlation (A) 12138, the second cross correlation (B) 12139, the phase-insensitive cross correlation 12140, and the phase-insensitive cross correlation angle 12141 are shown in FIG. 133. The cross correlation results are calculated from the two sets of sinusoids of values ​​12106, 12116 plotted in FIG. 132. The phase difference between the two sets of sinusoids changes over time in a manner that may be similar to the changing phase relationship between the variable valve command signal 12105 (FIG. 134) and the drive chamber pressure signal 12115 in a reciprocating positive displacement pump. One possible theory for the changing phase angle between the variable valve command signal 12105 and the pressure signal is that as the pump chamber 111 fills with fluid, the drive chamber volume becomes smaller, or as the pump chamber 111 empties, the drive chamber volume becomes larger, thereby changing the pressure responsiveness to the valve command.

[0337] The phase-insensitive cross correlation 12140 remains approximately constant regardless of changes in the phase angle between the two signals 12106 and 12116. The first cross correlation value 12138 and the second cross correlation value 12139 vary significantly as the phase angle changes between the two signals.

[0338] One exemplary use of this phase-insensitive correlation coefficient is shown in FIG. 134. In the figure, pressure data and correlation values ​​are plotted for the delivery and fill strokes of a pressure-driven reciprocating pump using the hardware described in FIG. 11A. The delivery stroke can be initiated by controlling one or both of the variable valves 117, 118 to pressurize the drive chamber 112 to a desired pressure, as measured by the sensor 114. Once the pressure rises to the desired level 12110, the pressure is controlled solely by the positive pressure variable valve 117. The control signal to the positive pressure variable valve 117 can be a function of the variable valve signal during pressurization and the currently measured pressure. The restriction or opening of the positive pressure variable valve can be sinusoidally varied (12105) to produce a responsive change in the measured pressure signal 12115. In one embodiment, the controller 119 can be programmed to initiate the correlation coefficient calculation (as described above) after a number of cycles to allow the signal to stabilize.

[0339] A high correlation number 12140 may indicate that the measured pressure is tracking the variable valve command signal and that the diaphragm is moving. The controller may store the maximum correlation number 12145 during the stroke. The integral of the correlation number 12150 over time may further provide a measure of the amount of liquid displaced by the pump 110.

[0340] In one exemplary method, the physical end of stroke for a membrane-type pressure-driven reciprocating pump for a delivery stroke may be defined as occurring when the membrane 109 displaces all or most of the liquid in the pump 101 and reaches the limit of its displacement against the wall of the pump chamber. The designated end of stroke may be defined as the point in time when the correlation coefficient number is approximately zero. At the physical end of stroke, the volume of the drive or control chamber 112 is fixed and the pressure within the chamber can stop fluctuating in response to the valve command signal. At the designated end of stroke 12160, the correlation coefficient number 12140 drops to zero within a short period of time after the pressure signal 12115 loses its periodicity. Although slightly delayed from the physical end of stroke, the designated end of stroke based on the correlation coefficient number more reliably indicates the physical end of stroke because it is less susceptible to signal noise and variability due to signal strength.

[0341] The fill stroke follows a similar process to the deliver stroke. The fill stroke begins when one or both of the variable valves 117, 118 bring the drive chamber 112 to the desired low pressure 12102. Once the pressure drops to the desired low pressure, the drive pressure can be controlled solely by the vacuum variable valve 118. The control signal to the vacuum variable valve 118 can be a function of the variable valve signal during pressurization and the currently measured pressure. The vacuum variable valve command signal can vary sinusoidally to produce a responsive change in the measured pressure. To improve the reliability of the calculation, the controller 119 can be programmed to begin calculating the correlation coefficient (as described above) after a number of cycles. In one exemplary method, for a membrane-type pressure-driven reciprocating pump, the physical end of the stroke for the fill stroke can be defined as occurring when the pump chamber fills with liquid and the membrane 109 reaches the limit of its displacement against the wall of the drive chamber. The designated end of the stroke can be defined as the point at which the correlation coefficient is approximately zero. At the physical end of the stroke, the volume of the actuation chamber 112 is fixed near zero and the pressure within the chamber stops fluctuating in response to the valve command signal. At the specified end 12165 of the stroke, the correlation coefficient 12140 drops to zero within a short period of time as the pressure signal loses its periodicity.

[0342] The dialysis machine is permeable to pressure waves generated by the internal dialysate pump and blood pump. The cross-correlation procedure tends to reject pressure signals in the dialysate pump that are at frequencies sufficiently different from the variable valve command signal, for example. Therefore, by programming the controller to vary the variable valve command signals of the dialysate pump and blood pump at different frequencies, the calculation of correlation coefficients for the internal dialysate pump and blood pump can be separated from each other.

[0343] The controller 119 can declare an end of stroke 12160, 12165 when the correlation number 12140 falls below a predetermined percentage of the maximum correlation number 12145. In another implementation, the controller can declare an end of stroke 12160, 12165 when the correlation number 12140 falls below a predetermined percentage of the maximum correlation number 12145 and does not increase over time. In another example, a specified end of stroke can be declared when the correlation number 12140 falls below a predetermined percentage of the average correlation number for a predetermined time interval during a pump stroke (without the further proviso that the value no longer increases over a predetermined period of time). In another implementation, the controller can declare an end of stroke 12160 when the correlation number 12140 falls below a predetermined threshold. In another implementation, the controller can declare an end stroke 12160 when the correlation number 12140 falls below a predetermined threshold and is not increasing over time.

[0344] The instantaneous flow rate from the pump may be determined from the correlation coefficient number during most of the pump stroke. The flow rate may be proportional to the correlation coefficient number. FIG. 131 shows three exemplary pressure traces 12050, 12052, 12054 in the actuation chamber 112 in response to a sinusoidally varying restriction 12020 in the valve 117. The pressure responses 12050, 12052, 12054 in the actuation chamber 112 tend to track the changing restriction of the variable valves 117, 118 as the actuation chamber volume changes as the membrane 109 moves. When flow from the fluid side of chamber 111 stops during a delivery stroke, pressure trace 12050 is an example of a pressure response. When flow stops, the volume of actuation chamber 112 becomes constant and the chamber fills until pressure 12050 reaches tank pressure 12051. If the volume of the actuation chamber 112 is constant, changing the restriction of the inlet valve 117 only changes the rate of pressure increase. Pressure trace 12054 is an example of a pressure response when the flow of fluid from the pump is relatively unrestricted; here, the membrane may be moving rapidly and the actuation chamber volume may be increasing rapidly, so restricting the air flow significantly reduces the pressure 12054 in the chamber 112. Pressure trace 12052 is an example of a low flow rate, where the pressure 12052 in the chamber changes only slightly as the valve restriction 12020 changes. The correlation coefficient is proportional to the amplitude of the pressure waveform for a given amplitude of the variable valve restriction. A pressure wave with a large amplitude may indicate a fast membrane movement and a high flow rate of fluid into and out of the pump. Therefore, a high correlation coefficient may be proportional to the flow rate. Benefits of this method of measuring instantaneous flow include improved treatment reliability, increased treatment accuracy, better flow control, and lower instrument costs.

[0345] In another implementation, the controller can declare the end of a stroke when the correlation value 12141 is undefined. The controller can calculate the progress of the stroke from the value of the correlation angle. The instantaneous flow rate may be calculated from the rate of change of the correlation angle 12141.

[0346] An occlusion is considered to exist when fluid flow into or out of the pump chamber is restricted. As shown in FIG. 135, partial and complete occlusions can be detected based on the correlation number as calculated above. A partial occlusion can result in a low correlation number and a low integrated correlation number. The controller 119 can compensate for the partial occlusion by commanding more pump strokes or increasing the maximum applied pressure. A complete occlusion can resemble the end of the stroke and can result in a similar response in the correlation number, integrated correlation number, and correlation angle. In one embodiment, the controller can monitor for occlusion detection by tracking the correlation between strokes and the integrated correlation number. For example, a complete occlusion can be declared if any of the maximum correlation number 12145, integrated correlation number 12150, or absolute value of the correlation angle at the end of the stroke has decreased by a predetermined amount from the value of the previous full stroke (e.g., a decrease to less than about 70% of the value of the previous full stroke). In another embodiment, a complete occlusion may be declared when the absolute value of the maximum correlation number, integrated correlation number, or correlation angle at the end of a stroke is less than 90% of the value of a complete stroke for three consecutive strokes. The absolute value of the maximum correlation number, integrated correlation number, or correlation angle for a complete stroke at the end of a stroke can be obtained from the most recent complete stroke. In another embodiment, a complete occlusion may be declared if the absolute value of the maximum correlation number, integrated correlation number, or correlation angle at the end of a stroke is less than a predetermined minimum value for at least two strokes. This last test can be used, for example, to detect chambers that are occluded from the start, making stroke-to-stroke comparisons difficult at best. Variable Valve Calibration The variable valves can be calibrated to determine the minimum current required to open the valve for a given pressure differential across the valve. This minimum current may be referred to as the cracking current. In an embodiment, the cracking current may vary linearly with the pressure difference between the drive chamber 112 and the tanks 121, 122. A mathematical relationship between the measured pump drive chamber pressure 114 and the cracking current may be established through a calibration procedure. In one example, one or both of the variable valves 117, 118 are used to establish a predetermined backpressure in the drive chamber 112. After both valves close, the current to one valve is increased as the pressure in the drive chamber is measured by the pressure sensor 114. The cracking current is the measured current when the measured pressure is found to increase as the current delivered to the valve gradually increases. The cracking current may be determined for two or more predetermined backpressures, and the controller can use this data to adapt an equation relating the valve's cracking current to the existing backpressure in the pump drive chamber. In one embodiment of a pump and valve system, the equation may be a linear equation.

[0347] In one aspect of the calibration procedure, the controller determines the cracking current for each variable valve associated with the pump at four initial backpressure values ​​in the pump drive chamber. This determination may be repeated multiple times (e.g., three times for a total of 12 measurements). The controller may be programmed to ignore outlier current values ​​and use the remaining data to develop a linear equation for cracking current as a function of initial backpressure. Reducing fluid imbalance caused by air bubbles in the dialysate The release of air or other gases from either fresh or used dialysate can cause a cumulative imbalance between the volume of fresh dialysate pushed through the dialyzer by the balance chamber and the volume of used dialysate in the balance chamber used to push the fresh dialysate. For example, if air bubbles cannot escape from the passageway on the used dialysate side of the balance chamber, they can alternately expand and contract, expelling additional volumes of used dialysate from the balance chamber not occupied by the fresh dialysate being forced into the dialyzer. As the internal dialysate pump pushes used dialysate into the balance chamber and an equal volume of fresh dialysate is being forced into the dialyzer, the air bubbles are compressed by the pump pressure. However, at the end of a pump stroke, when the pressure in the balance chamber drops, the air bubbles can expand, expelling an additional small amount of used dialysate from the balance chamber outlet. This additional small amount of spent dialysate accumulating over many pump strokes and attempting to exit the spent dialysate side of the balance chamber can result in a significant imbalance between the fresh dialysate being forced into the dialyzer and the fresh dialysate being expelled to drain. In one embodiment, this potential fluid imbalance can be mitigated by ensuring that the expansion of air bubbles at the end of an internal dialysate pump stroke pushes dialysate back into the pump chamber rather than the drain line. The procedure for mitigating this unoccupied fluid flow can be illustrated by considering the transfer stroke from pump 162 to balance chamber 342 in FIG. 5. At the end of the pump stroke to fill balance chamber 342 with dialysate from pump 162, outlet (drain) valve 222 is closed. Balance chamber 342 can then lock fluid by closing valves 231 and 221 while leaving transfer pump outlet valve 213 open. The controller can then release the air pressure in transfer pump 162, allowing any air bubbles in the flow path to the balance chamber to expand. Any liquid displaced by the expanding bubble will be free to travel back towards the pump 162 rather than to drain.Finally, the controller can close the transfer pump outlet valve 213 and open valve 222 to prepare the dialysate in balance chamber 342 for drain. This same procedure can be applied to pump 161 and balance pump 341. A similar procedure can also be used on the fresh dialysate side of balance chambers 341, 342. In that case, the controller can release pressure in the external dialysate pump at the end of its pump stroke to fill one of the balance chambers, while the valve between the external dialysate pump and the balance chambers remains open. Any expanding air bubbles in the flow path between the external dialysate pump and the balance chambers will tend to push the dialysate back toward the pump rather than downstream toward the dialyzer. Short strokes in blood pumps The pod pump 180 (FIG. 3A) in the blood cassette can perform shortened strokes to reduce damage to blood elements. Damage to blood elements can be reduced by ensuring that the membrane in the pod pump does not completely touch the pump chamber wall at the end of the pump stroke. The blood pump may be short-stroked while the system controller monitors the blood flow rate and monitors for blockages. At the start of pump operation, a full stroke is performed to achieve steady-state flow and determine parameters used to control the short stroke, including the required delivery pressure, required fill pressure, and time to fill the pump chamber. The flow rate may be determined from the time required to deliver fluid to fill the chamber. Steady-state flow conditions can be indicated by a) a change in average flow rate of less than about 3 ml / min, b) a maximum pump flow rate within about 15 ml / min of both fill and delivery pressure targets, and c) an average chamber delivery flow rate within about 10% of the pump flow rate at the minimum driving pressure.

[0348] The controller can short-stroke the blood pump by reducing the delivery stroke to a predetermined percentage (e.g., about 80%) of the delivery pressure determined in the steady-state phase. The reduced pressure allows the delivery stroke to be completed, for example, about 90%, by the time the pump diaphragm turns and the nearly empty chamber begins the pump fill stroke. When the chamber performing the fill stroke reaches the end of the stroke, the pump diaphragm turns. The fill stroke occurs at the pressure determined by the controller in the steady-state phase. Short-stroke behavior can be monitored by examining the maximum and integrated correlation coefficients and the time to end stroke of the same chamber during subsequent fill strokes. The controller 119 (FIG. 11a) can monitor the time to fill the pump using the end-stroke detection algorithm described above. The controller 119 can adjust the delivery pressure in the drive chamber 112 so that the time to fill the chamber is 90% of the full time determined in the steady-state phase. Alternatively, the integrated correlation value may be monitored and the end of fill is deemed to be, for example, 90% of the integrated correlation number corresponding to the completion of the final stroke period.

[0349] The blood pump 101 and controller 119 can use the correlation number during the fill stroke to detect a complete occlusion, either upstream or downstream of the pump, during the short stroke. A complete occlusion downstream will leave more blood in the chamber, thereby shortening the fill time. An end stroke may be detected by a large drop in the correlation number. A short fill time may be detected by a low integrated correlation number. Similarly, an occlusion upstream of the pump will result in a large drop in the correlation number and a lower integrated correlation number.

[0350] The short stroke regimen assumes a constant delivery impedance. However, changes in flow resistance across the dialyzer 14 or blood line, or changes in patient access, can cause the blood pump to perform a full stroke. This problem can be mitigated by relearning the required delivery pressure, fill pressure, and fill time by returning to a full stroke every 100 strokes. If the delivery and fill impedances have not changed, a check may require as few as eight full strokes. To limit hemolysis, the controller 112 may terminate therapy if an excessive number or percentage of blood pump strokes are full strokes. In one example, the controller 112 terminates therapy if more than 200 full strokes occur, or if 20% of the strokes after the initial steady-state phase are full strokes. PWM valve EOS, blockage and back pressure detection A positive or negative pressure source connected to the pod pump's drive chamber via a pulse valve and a pressure sensor coupled to the pod pump's drive chamber may be used to determine pump operating parameters, including end of stroke, occlusion, and fluid pressure upstream and downstream of the pump. One exemplary configuration is shown in FIG. 136 . A two-way valve 12260 may be required to provide positive pressure to the drive chamber 12214 of the pod pump 12212 via the fluid management system valve 12240 to transfer fluid from the pump through the valve 12220. The fluid management system valve 12240 may be rapidly opened and closed to gradually increase the pressure in the drive chamber 12214. A tightly coupled pressure sensor 12230 may measure the air pressure in the chamber 12214 and transmit that pressure to the controller 12270. A fluid management system volume 12242 and a fluid management system pressure sensor 12244 may be present but are not used in this example.

[0351] The controller can control the opening and closing of the fluid management system valve 12240 and record data from the pressure sensor 12230 to generate a time history of the valve operation 12310 and resulting pressure 12315 in the actuation chamber as shown in FIG. 137. The valve may be pulsed periodically, with the frequency, open duration, and closed duration controlled by the controller 12270. The operating frequency may be selected heuristically. The frequency may be low enough to distinguish between membrane movement and system compliance. The frequency may be selected to be high enough to meet the maximum required flow rate, while being low enough to allow fluid to be displaced.

[0352] The response of the membrane 12215 and the flow from the pump 12212 can be monitored analytically by summing the pressure drop during each pump stroke (FIG. 138). When the fluid management system valve 12240 closes, the controller can calculate the change in pressure between each time step or sample and sum the difference over a period of valve closure as follows:

[0353] ΔP CH =Σ(P i -P i-1 ) The pressure data may be filtered to remove signal noise. The chamber pressure may be low-pass filtered before calculating the pressure change. Positive pressure changes may be removed from the sum. When the fluid management system valve 12240 opens, the pressure sum 12320 may be reset to zero 12321. The controller 12270 can detect fluid flow from the pump when the absolute value of the sum of the pressure changes 12320 exceeds a defined value 12325. The controller can detect the end of a stroke with a first sum 12320 not meeting the defined value after the sum exceeds the defined value 12325. The controller can command the fluid management system valve 12240 to remain open to ensure all fluid is expelled from the pod pump 12212. The fluid management system valve 12240 is left open to improve stroke-to-stroke repeatability, which in turn improves flow rate accuracy.

[0354] The hardware configuration of FIG. 138 and the pressure data of FIGS. 137 and 138 can provide information about the fluid pressure downstream of the pod pump. Fluid will not flow out of the pod pump until the air pressure in the actuation chamber 12214 is greater than the fluid pressure downstream of the pump 12212 and valve 12220. The controller 12270 can detect fluid flow and membrane movement when the absolute value of the sum of the pressure changes 12320 exceeds a defined value 12325, as occurs in step 12317. The controller can store the average of the pressure 12315 during this step 12317 as the downstream pressure. Alternatively, the pressure at the end of step 12317 before the fluid management system valve reopens can be stored as the downstream pressure.

[0355] A complete blockage downstream of the pod pump 12212 may be determined using the hardware configuration of FIG. 136 and the pressure plots of FIGS. 137 and 138. A blockage downstream of the pump 12212 may be declared by the controller 12270 when no fluid flow or membrane movement is detected as the pressure at the driving pressure is increased to the maximum pressure 12312. The controller determines that no fluid has flowed when the pressure sum 12320 does not exceed a given value 12325.

[0356] The hardware configuration of FIG. 138 and the pressure data of FIG. 139 can provide information about the fluid pressure upstream of the pod pump during a fill stroke. The fill stroke can be initiated by opening the two-way valve 12250 and supplying negative pressure to the actuation chamber 12214 of the pod pump 12212 via the fluid management system valve 12240 to draw fluid into the pump via the valve 12210. The fluid management system valve 12240 can rapidly open and close to gradually increase the pressure in the actuation chamber 12214. A tightly coupled pressure sensor 12230 can measure the air pressure in the chamber 12214 and transmit that pressure to the controller 12270. The controller can control the opening and closing of the fluid management system valve 12240 and record the data from the pressure sensor 12230 to generate a time history of the valve operation and resulting pressure 12315 in the actuation chamber, as shown in FIG. 139.

[0357] Fluid will not flow into the pod pump until the air pressure in act...

Claims

1. 1. A system for flushing a fluid flow path coupled to a pair of diaphragm pumps, comprising: first and second diaphragm pumps, each of said diaphragm pumps having a pump chamber separated from an actuation chamber by a flexible diaphragm, each of said actuation chambers being selectively connectable to a source of positive or negative pressure by operation of a controller; a first fluid flow path coupling an inlet of the first diaphragm pump through a first inlet valve to an inlet of the second diaphragm pump through a second inlet valve; and a second fluid flow path coupling an outlet of the first diaphragm pump through a first outlet valve to an outlet of the second diaphragm pump through a second outlet valve. the inlet valve and the outlet valve each include a valve selectively coupled to a pressure source of positive pressure or negative pressure by operation of the controller; the controller directs a negative pressure to be applied to a diaphragm of the first diaphragm pump when emptied of fluid and a positive pressure to be applied to a diaphragm of the second diaphragm pump when filled with fluid while the first and second inlet valves are open and the first and second outlet valves are closed to clear the first fluid flow path or while the first and second inlet valves are closed and the first and second outlet valves are open to clear the second fluid flow path.

2. 2. The system of claim 1, wherein the controller then applies a negative pressure to the diaphragm of the second diaphragm pump when it is emptied of fluid and a positive pressure to the diaphragm of the first diaphragm pump when it is filled with fluid to reverse fluid flow between the first and second diaphragm pumps.

3. 3. The system of claim 2, wherein the controller applies alternating positive and negative pressures to the diaphragms of the first and second diaphragm pumps to move fluid flow in both directions between the first and second diaphragm pumps.

4. 2. The system of claim 1, wherein the controller applies a negative pressure to a diaphragm of the first diaphragm pump and a positive pressure to a diaphragm of the second diaphragm pump while opening the first and second inlet valves to clear the first fluid flow path after closing the first and second inlet valves and the first and second outlet valves or while opening the first and second outlet valves to clear the second fluid flow path.

5. 3. The system of claim 2, wherein the controller applies a positive pressure to a diaphragm of the first diaphragm pump and a negative pressure to a diaphragm of the second diaphragm pump while opening one of the first or second inlet valves to clear the first fluid flow path after closing the first and second inlet valves and the first and second outlet valves, or while opening the first and second outlet valves to clear the second fluid flow path.

6. 6. The system of claim 5, wherein the controller applies alternating positive and negative pressures to the diaphragms of the first and second diaphragm pumps to move fluid flow in both directions between the first and second diaphragm pumps.

7. 2. The system of claim 1, wherein the second fluid flow path is coupled to a hemodialysis inlet of a dialysis unit and a hemodialysis outlet is coupled to a venous line that may be coupled to a drain after passing through an occluder, and the controller closes the occluder when the first and second outlet valves of the first and second diaphragm pumps are opened to allow liquid to flow into the second fluid flow path between the first and second diaphragm pumps.

8. 8. The system of claim 7, wherein the dialysate inlet and the dialysate outlet of the dialysis device are coupled to a fluid balance circuit via a plurality of dialysate-side valves, and the controller closes the dialysate-side valves when the first and second outlet valves of the first and second diaphragm pumps are open.

9. 2. The system of claim 1, wherein the first fluid flow path is coupled to an arterial line that may be coupled to a drain after passing through an occluder, and the controller closes the occluder when the first and second inlet valves of the first and second diaphragm pumps are opened to allow liquid to enter the first fluid flow path between the first and second diaphragm pumps.

10. The controller:

10. The system of claim 9, further comprising the steps of draining and emptying the first or second diaphragm pump filled with fluid by closing the outlet valve of the first or second diaphragm pump filled with fluid, opening the inlet valve of the first or second diaphragm pump filled with fluid, closing the inlet valve of a corresponding first or second diaphragm pump being emptied, and opening the occluder in the arterial line.

11. 9. The system of claim 8, wherein the controller supplies fluid to the first or second diaphragm pump by opening one of the plurality of dialysate side valves coupled to the fluid balance circuit, opening the outlet valve of the first or second diaphragm pump, and applying negative pressure to a diaphragm of the first or second diaphragm pump designated by the controller to receive fluid.

12. the venous line is coupled to the drain via a drain valve, the first fluid flow path is coupled to an arterial line which is coupled to the drain via a drain valve, the venous line is coupled to the arterial line via an arterial-venous valve, the controller closes the drain valve and opens the arterial-venous valve; and (a) opening the outlet valve and closing the inlet valve of the first or second diaphragm pump when it is filled with fluid, opening the inlet valve of the second or first diaphragm pump when it is emptied, and simultaneously applying a positive pressure to the first or second diaphragm pump and a negative pressure to the emptied second or first diaphragm pump; or 8. The system of claim 7, further comprising: (b) opening the inlet valve and closing the outlet valve of the first or second diaphragm pump that is filled with fluid; closing the inlet valve of the second or first diaphragm pump that is emptied; and applying a negative pressure to the second or first diaphragm pump that is emptied simultaneously with applying a positive pressure to the first or second diaphragm pump.

13. 2. The system of claim 1, wherein the controller causes the first and second inlet valves to open and the first and second outlet valves to close, then applies a negative pressure to a diaphragm of the first diaphragm pump while the first and second inlet valves are open, and then applies a positive pressure to a diaphragm of the second diaphragm pump to wash the first fluid flow path while the first and second inlet valves are open and the first and second outlet valves are closed.

14. 2. The system of claim 1, wherein the controller causes the first and second inlet valves to close and the first and second outlet valves to open, then applies a negative pressure to a diaphragm of the first diaphragm pump while the first and second outlet valves are open, and then applies a positive pressure to a diaphragm of the second diaphragm pump to wash the first fluid flow path while the first and second outlet valves are open and the first and second inlet valves are closed.

15. The controller:

8. The system of claim 7, further comprising the steps of draining and emptying the first or second diaphragm pump filled with fluid by closing the inlet valve of the first or second diaphragm pump filled with fluid, opening the outlet valve of the first or second diaphragm pump filled with fluid, closing the outlet valve of a corresponding first or second diaphragm pump being emptied, and opening the occluder of the venous line.

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