Fluid balancing system

Abstract

To provide various systems and methods for performing hemodialysis more efficiently, easily and / or at a lower cost.SOLUTION: A hemodialysis system (6000) comprises a dialysis unit (6001) and a user interface unit (6002) for displaying safety-critical information about a dialysis process. The hemodialysis system may include a dialysate flow path that includes a balancing circuit, a mixing circuit, and / or a directing circuit. The circuits may be defined in one or more cassettes. The fluid circuit may be at least partially spatially and / or thermally isolated from electrical components of the system. A gas supply is provided in fluid communication with the dialysate flow path and / or the dialyzer to force dialysate through the dialyzer and return blood to the patient.SELECTED DRAWING: Figure 61

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. [Background technology]

[0002] 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 treatment and patient outcomes.

[0003] 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.

[0004] 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. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] International Publication No. 2004 / 041081 Summary of the Invention [Problem to be solved by the invention]

[0006] SUMMARY OF THE INVENTION It is an object of the present invention to provide various systems and methods that can make hemodialysis more efficient, easier, and / or less expensive. [Means for solving the problem]

[0007] 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.

[0008] In one embodiment, the system includes four flow paths: blood, internal dialysate, external 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 located in respective cassettes. In yet another embodiment, two or more flow paths are included in a single cassette. In one embodiment, a hemodialysis system is provided having at least two flow paths, which are 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 in a single cassette. In yet another embodiment, a hemodialysis system is provided including a blood flow path through which untreated blood is pumped from a patient, passed through a dialyzer, and treated blood is returned to the patient. The blood flow path includes at least one blood flow pump disposed in 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 for delivering 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 can include 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 and through the dialyzer. The dialysate flow path includes at least one pneumatic pump. In one aspect, the invention relates to a hemodialysis system. In one embodiment, the hemodialysis system includes a blood flow path, a first cassette that defines an internal dialysate flow path, a dialyzer in communication with the blood flow path and the internal dialysate flow path, a second cassette that defines an external dialysate flow path, and a membrane that connects the first cassette to the second cassette.

[0011] 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.

[0012] 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.

[0013] 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.

[0014] In some embodiments, the hemodialysis system includes a blood flow path through which blood is pumped from a patient and passed through a 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 includes a dialysate pump; and a control fluid path through which a control fluid drives the blood flow pump and the dialysate pump.

[0015] 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.

[0016] 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.

[0017] 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.

[0018] 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.

[0019] 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.

[0020] 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.

[0021] 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.

[0022] 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.

[0023] 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.

[0024] 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 passes through the 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 that communicates with the dialyzer and includes at least one dialysate system valve; and a heater that heats the dialysate. Another aspect of the present invention relates to a valve system. In one embodiment, the valve system includes a valve housing containing multiple valves, at least two of which each have a valve chamber and a drive chamber. Each of the at least two valves is driven by a control fluid in the drive chamber. The valve system further includes a control housing having multiple fluid interface ports for communicating with the control fluid from a base unit, and multiple 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 drive chambers, thereby allowing the base unit to drive the valve by pressurizing the control fluid in the fluid interface port. In one embodiment of the present invention, the valve includes a first plate, a second plate, a third plate, and a diaphragm. 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 plate and the third plate. A partition is disposed within the recess between the first plate and the second plate. The partition has an edge, and the edge is held within the groove. The second plate includes a valve seat. The partition is pressed by air pressure to seal and hermetically 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 plate and the third plate. In an embodiment, a passage for generating air pressure is disposed between the first plate and the second plate.

[0025] In a further aspect of the present invention, a pump system is disclosed. 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.

[0026] 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.

[0027] 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 a supply inlet, fluid from the supply outlet flows to a supply line, fluid from the return line flows to a return inlet, and fluid from the return outlet flows to a cassette outlet. In other embodiments, the pumping 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.

[0028] In some embodiments, the pump mechanism includes a pod pump comprising a rigid spheroidal wall defining a rigid pump volume and having an inlet and an outlet, a pump diaphragm disposed within the spheroidal wall and connected to the spheroid, and a port connecting the pod pump to a pneumatic drive system for actuating the diaphragm to move fluid in and out of the pump volume. In some embodiments, the pump diaphragm separates the fluid from a gas in communication with the pneumatic drive system. In some embodiments, the balance chamber includes a rigid spheroidal wall defining a balance volume and a balance diaphragm disposed within the spheroidal wall and connected to the spheroid. In some embodiments, the balance diaphragm 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 includes a valve mechanism disposed at each of the supply side and return side inlet and outlet. The valve mechanism is pneumatically actuated. A cassette is disclosed in a further aspect of the present invention. 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 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 communicates with the first flow path, and the second compartment communicates with the second flow path.

[0029] 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 communicates with the control fluid path, and the second compartment communicates with the second fluid path. In yet another embodiment, the cassette includes a rigid container including a first fluid path connecting the first inlet to the first outlet, a second fluid path connecting the second inlet to the second outlet, and a partition separating the rigid container into the first and second compartments. In operation, the first compartment communicates with the first fluid path, and the second compartment communicates with the second fluid path.

[0030] A further aspect of the present invention discloses a pump. In one embodiment, the pump includes a first rigid element, a second rigid element, and a diaphragm 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 a diaphragm, and further at least partially define a fluid path to the pod pump chamber. The diaphragm surrounds the pod pump chamber. 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 and second compartments are not in communication with each other. Movement of the diaphragm by fluid entering the first compartment causes pumping of fluid within the second compartment.

[0031] 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 that receives pressure information from the drive chamber pressure transducer and controls the variable valve to thereby generate a control pressure in the drive chamber. The control pressure is less than or equal to the first pressure. A further aspect of the invention discloses a method. In an embodiment, the method includes 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.

[0032] 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.

[0033] 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 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 measured volume of gas at the dialyzer. In another embodiment, the method is for measuring the clearance rate of a dialyzer. In one embodiment, the method includes applying a pressure differential across the dialyzer, measuring the flow rate of the dialyzer, and determining the clearance rate of the dialyzer based on the pressure differential and the flow rate. In another embodiment, the method is for measuring the clearance rate of a dialyzer. In one embodiment, the method includes passing water through a dialyzer, measuring the amount of ions collected by the water after passing through the dialyzer, and determining the cleaning rate of the dialyzer based on the amount of ions collected by the water after passing through the dialyzer. In another embodiment, the method includes passing water through a dialyzer, measuring the conductivity of the water, and determining the cleaning rate of the dialyzer based on the change in the conductivity of the water.

[0034] 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.

[0035] In one embodiment, the method includes providing a hemodialysis system having 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 to the dialyzer, communicating the blood flow path with 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. In another embodiment, the method includes providing a hemodialysis system having 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 to the dialyzer, communicating the blood flow path with the dialysate flow path, and passing a gas through the dialysate flow path to circulate the blood in the blood flow path.

[0036] 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.

[0037] 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.

[0038] 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 about the dialysis process via the user interface using the safety-critical information.

[0039] 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, in response to the input, transmitting a request for safety-critical information from the user interface computer to an automation computer associated with a dialyzer, 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.

[0040] 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.

[0041] In another aspect of the invention, a method of forming, for example, one or more hemodialysis systems is disclosed. In a further aspect of the invention, a method of using, for example, one or more hemodialysis systems is disclosed.

[0042] 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. [Brief explanation of the drawings]

[0043] [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] FIG. 10 illustrates 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 the display unit and the 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 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 and 62B are schematic diagrams illustrating normal and alarm screen displays that may be displayed on the user interface shown in FIG. 61. DETAILED DESCRIPTION OF THE INVENTION

[0044] 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.

[0045] 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 force 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.

[0046] 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.

[0047] 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.

[0048] 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. In some embodiments, it is 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 to remove contaminants, infectious organisms, and debris, using, for example, an ultrafilter. 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.

[0049] 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 dialysate, including using appropriate concentrations of salts, osmolality, pH, etc., is well known to those skilled in the art. As described in more detail below, dialysate need not be prepared to the same concentration as the dialysate used to treat blood. For example, dialysate can be formed simultaneously with or prior to dialysis and contained within a dialysate storage container or the like.

[0050] 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.

[0051] 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.

[0052] 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.

[0053] 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.

[0054] 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 with 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 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.

[0055] 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.

[0056] 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 may include 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.

[0057] 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 a 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 is controlled and end-of-stroke is detected as described below. The blood flow cassette 22 further includes an integrally formed spike for receiving a vial of anticoagulant.

[0058] 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.

[0059] 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.

[0060] The elements shown in FIG. 3A are described below. Briefly, the blood flow circuit 141 includes an anticoagulant supply 11 and a blood flow pump 13 that pumps blood from the patient to the dialyzer 14. While the illustrated anticoagulant supply 11 is located 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. The anticoagulant supply 11 is located downstream of the blood flow pump 13. The balancing circuit 143 also includes a dialysate pump 15 that pumps dialysate to the dialyzer 14 and a bypass pump 35. The directing circuit 142 includes a dialysate pump 159 that pumps dialysate from the dialysate tank 169 through the heater 72 and / or ultrafilter 73 and into the balancing circuit. The directing circuit 142 pumps waste from the balancing circuit 143 to a drain 31.

[0061] In one embodiment, blood flow circuit 141 is connected to directing circuit 142 through conduit 67, e.g., for sterilization, as described below. Dialysate flows from a dialysate supply to dialysate tank 169. As shown in FIG. 3A, in one embodiment, dialysate is formed in mixing circuit 25. Water from water supply 30 flows into mixing circuit 25 through directing circuit 142. Dialysate ingredients 49 (e.g., bicarbonate and acid) are further added into mixing circuit 25, and a series of mixing pumps 180, 183, and 184 are used to form the dialysate. The dialysate is then transported to directing circuit 142.

[0062] 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.

[0063] An example of a blood flow circuit is shown in FIG. 4. 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. 4, 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 any 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.

[0064] As shown in FIG. 4, the blood flow cassette 141 further includes one or more blood flow pumps 13 for moving 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. 4. 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.

[0065] 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.

[0066] 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 reverse flow). 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.

[0067] 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.

[0068] 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 and 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.

[0069] 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.

[0070] 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 is vented to atmosphere for the FMS system measurements. Alternatively, the system may be vented to a high pressure positive source and a low pressure negative source for the FMS system measurements. This provides the following advantages: (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 larger pressure differences for the FMS system measurements, resulting in better answers.

[0071] 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 that has been released from the blood by 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.

[0072] 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 thus 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 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 and exiting 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 exit 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 liquids, drugs, or other compounds into the blood circuit. If needle access is anticipated, a sealed rubber-type stopper can be used. The use of a self-sealing stopper with a dividing septum allows for sample extraction and fluid transfer using a needleless system.

[0073] 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 in its entirety, and which is further described below.

[0074] 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.

[0075] 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 a pod pump 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.

[0076] 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. The elevated flow paths 908, 910 therefore 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 shown herein for the raised channels, pod pumps, valves, and other aspects are exemplary and illustrative only. Other embodiments are apparent.

[0077] 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.

[0078] 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.

[0079] 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.

[0080] 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 figure.

[0081] 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, diaphragm 1220 completes valves 808, 814, 816, and 822, and diaphragm 1226 completes 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 diaphragm is pulled away from the hole and liquid is drawn in. When the diaphragm is pressed toward the hole, liquid is forced through. Fluid flow is directed by opening and closing valves 808, 814, 816, 822, 832, 834, and 836.

[0082] 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 the second fluid from metering pump 830 to point 826 in the fluid line.

[0083] 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.

[0084] Figures 32A and 32B show the interior of bottom plate 1100. The interior of pod pumps 820 and 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 and 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 exterior of bottom plate 1100. The air source is attached to this side of the cassette. In one embodiment, tubing connects the valves and the face of pump 1102. In some embodiments, the valves are ganged, with more than one valve driven by the same air line.

[0085] 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 mounted 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.

[0086] 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.

[0087] 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 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.

[0088] 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 pumps 15 in this figure include 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 partition separating the chamber into two separate fluid compartments, configured so that fluid entry into one compartment results in fluid exit 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 sets, so that all valves in a set open and close simultaneously.

[0089] 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, and 242, valves 211, 212, and 213 are ganged and valves 241 and 242 are ganged. Similarly, in a second synchronized and controlled set of valves 221, 222, 223, 231, and 232, valves 221, 222, and 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, and 242 are open, and the second ganged set of valves 221, 222, 223, 231, and 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 exits 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 causes the fresh dialysate contained in balancing chamber 342 to exit balancing circuit 143 and enter dialyzer 14. Additionally, pod pump 161 draws spent dialysate from dialyzer 14 into pod pump 161. This is further shown in FIG. 18A.

[0090] 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.

[0091] 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 the septum. In each balance 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 entering and leaving the dialyzer are kept approximately equal.

[0092] 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 lines sufficient to cause leakage in already-closed downstream valves, 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.

[0093] When the septum approaches the walls of the balancing chambers (causing one of the balancing chambers to approach its minimum volume and the other to approach its maximum volume), positive pressure is applied to the first set of interlocking valves, causing them to close. Vacuum is applied to the second set of interlocking valves, causing them to open. The pod pump pumps dialysate into one of the other volumes of balancing chambers 341, 342. Again, an equal amount of dialysate is squeezed out of the other volume of the balancing chamber by the septum, forcing dialysate into the balance chamber volume. 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 entering and leaving the dialyzer are maintained equal.

[0094] 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.

[0095] 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 withdraw fluid from the patient.

[0096] 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.

[0097] 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.

[0098] 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 the stroke 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.

[0099] 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.

[0100] 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.

[0101] In therapy, it is preferable to keep the blood flow as constant as possible because stagnant blood flow can lead to blood clotting. Additionally, when the blood flow pump's transport fluid velocity is discontinuous, the balancing pump must frequently pause between strokes, which causes the dialysate fluid velocity to be discontinuous and / or slow.

[0102] 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.

[0103] 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.

[0104] 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.

[0105] 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.

[0106] 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.

[0107] Figures 35C and 35D are bottom views of the top plate 1000. The fluid channels are shown in this view. These channels correspond to the channels in the midplate 900 shown in Figure 34B. The top plate 1000 and the top of the midplate 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 midplate. 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.

[0108] 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 this example, the grooves 1002 form a passageway between the fluid inlet and fluid outlet sides of the pod pumps 820, 828 and balancing pods 812, 822.

[0109] The grooves 1002 provide a flow path between the inlet and outlet when the septum is at the end of the stroke so that 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).

[0110] In one embodiment, the liquid sides of the pod pumps 820, 828 and balancing pods 812, 822 include a feature that provides continuous inlet and outlet flow paths and a continuous outer ring 1004. This feature allows a seal (not shown) to be formed against the septum to be retained.

[0111] 35E is a side view of an embodiment of the top plate 1000, showing the continuous outer ring 1004 of the pod pumps 820, 828, and the balancing pods 812, 822. 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 midplate (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 midplate. 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 corresponding halves of the pod pumps 820, 828 and 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.

[0112] 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.

[0113] 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.

[0114] 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.

[0115] 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. In this example, directing circuit 142 can perform several different functions. 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.

[0116] 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.

[0117] 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, 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 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.

[0118] 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.

[0119] 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. A 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 Thermal Therapy System and Method," or U.S. patent application Ser. No. 11 / 787,212, filed April 13, 2007, and entitled "Fluid Pumping System, Device, and Method," both of which are incorporated herein in their entireties. Pod pumps are described in further detail below.

[0120] 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).

[0121] 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.

[0122] 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 temperature (as described below).

[0123] 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).

[0124] 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 and includes 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 duty cycle 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 ultrafiltration membrane or outlet temperature sensor; ErrorUF = difference between uf or outlet temperature sensor and desired temperature.

[0125] 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.

[0126] 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.

[0127] 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.

[0128] 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 disinfect and prevent the contaminants from reaching the patient's blood.

[0129] Directing circuit 142 can further direct spent dialysate through a balancing circuit to a drain, e.g., through contaminant line 39 in FIG. 6 to drain 31. 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.

[0130] 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, the 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.

[0131] Figures 41-45 show non-limiting examples of balancing cassettes. 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.

[0132] 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. Thus, 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.

[0133] 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.

[0134] 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 flow is permitted. 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. 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 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 pump 1102. In some embodiments, the valves are ganged and multiple valves are driven by the same air line.

[0135] 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.

[0136] 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 between 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.

[0137] Figure 45 is a cross-sectional view of valves 834, 836 of the assembled cassette, showing that in this embodiment, septum 1220 is assembled and positioned by being sandwiched between mid-plate 1000 and bottom plate 1100. Additionally, the cross-sectional view of Figure 45 shows valve 822 of the assembled cassette, showing that septum 1222 is positioned by being sandwiched between mid-plate 1000 and bottom plate 1100.

[0138] 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.

[0139] 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 each ingredient is added at the proper concentration when added to the mixing line.

[0140] 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.

[0141] 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.

[0142] 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.

[0143] FIG. 7B is a schematic diagram illustrating another example of a mixing circuit that may be provided in a cassette according to an embodiment. 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 the 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.

[0144] 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 make-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.

[0145] 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.

[0146] 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.

[0147] 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.

[0148] In Figures 38A and 38B, the pod pumps 820, 828 include grooves 1002 (which in alternative embodiments are grooves). The grooves 1002 shown 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 grooves in the walls of the internal pump chambers of the pod pumps.

[0149] 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.

[0150] 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 also includes a continuous feature (not shown). 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.

[0151] An embodiment of the midplate 1200 is shown in Figures 39A and 39B. The midplate 1200 is further illustrated 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.

[0152] 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 and 1316. In this embodiment, sensor cells 1314 and 1316 are included as areas of the cassette for the sensor elements. In one embodiment, the three sensor elements in two sensor cells 1314 and 1316 are housed in sensor element housings 1308, 1310, and 1312, and 1318, 1320, and 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 and 1322 house temperature sensor elements. 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.

[0153] 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.

[0154] 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 the 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 diaphragm (not shown) and an air or drive channel for mixing the liquids. Also shown are sensor cells 1314, 1316, which contain three sensor element housings 1308, 1310, 1312 and 1318, 1320, 1322.

[0155] 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.

[0156] 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 dividing each chamber into a first side and a second side, each side serving a different purpose as described above.

[0157] 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.

[0158] 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.

[0159] 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).

[0160] 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.

[0161] 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.

[0162] 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.

[0163] 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.

[0164] 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.

[0165] 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.

[0166] 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, the cassette does not include a pod pump, or a pod pump is 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.

[0167] 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 become 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 provide specific flow paths for 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.

[0168] 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.

[0169] 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).

[0170] 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.

[0171] 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.

[0172] 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 returns to the mixing cassette 500. Once 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.

[0173] FIG. 46D shows that mixing cassette 500 includes a pneumatic drive. Multiple valves and two pump chambers 8030, 8032 are provided in cassette 500 in the area designated by reference numeral 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 accuracy and because it is preferable to use smaller pumps so that full strokes, rather than partial strokes, can be used for control.

[0174] 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.

[0175] 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.

[0176] 46D and 46E show various pods 502, 504, 506, 602, 604, 702, 704, 706, and 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, or 704, a balance chamber pod 706 or 708, or a mixing chamber pod 504.

[0177] 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.

[0178] 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.

[0179] 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 and 708, and pod pumps 702 and 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, and 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.

[0180] 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.

[0181] 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.

[0182] 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.

[0183] 47A, 47D, and 47E show the chamber groove 906. The groove 906 is included in each half of the pod housing. In other embodiments, the groove is not included, and in some embodiments, the groove is included in only one half of the pod.

[0184] 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.

[0185] In various embodiments of the invention, one or more "pod pumps" are used for various purposes. The structure of the pod pump, as described above, is described 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.

[0186] 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.

[0187] Each half of the pod pump has at least one inlet valve and typically (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.

[0188] 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 thickness 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.

[0189] 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.

[0190] 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. Accordingly, the shape and dimensions of the septum will vary in various embodiments depending on these and other factors.

[0191] 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.

[0192] 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.

[0193] 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.

[0194] 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.

[0195] 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.

[0196] 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.

[0197] 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 expels fluid. Further, by controlling the valve in the second compartment, fluid is transported through the first valve and expelled through the second valve by the action of the control fluid.

[0198] 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 the conditions under which the pods are driven). 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.

[0199] In some embodiments, a pod pump is used that does not include a flexible dividing wall between chambers. In the above example, the pod pump can be used as a mixing chamber. For example, mixing chamber 189 in Figure 7A is such a pod pump.

[0200] 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.

[0201] 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.

[0202] 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.

[0203] 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.

[0204] 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.

[0205] 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 exit 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.

[0206] 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.

[0207] The septum 109 is formed with a lip 88 with a thickness 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.

[0208] 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.

[0209] 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.

[0210] 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).

[0211] 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.

[0212] 11A shows that controller 119 also receives pressure information from three pressure transducers: actuation chamber pressure transducer 114, positive pressure tank pressure transducer 115, and negative pressure tank pressure transducer 116. As their names suggest, these transducers measure the pressure in actuation chamber 112, positive pressure tank 121, and negative pressure tank 122, respectively. Controller 119 monitors the pressure in the two tanks 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 tanks 121, 122.

[0213] 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 actuation 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.

[0214] 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.

[0215] 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.

[0216] FIG. 11B shows another example of a pressure-actuated system 110 for a pod pump. In this example, pod pump 101 includes pump chamber 111, driver chamber 112, and a diaphragm 109 separating the 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.

[0217] 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. 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 from 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, may be driven by one-quarter reservoir pressure. 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 various 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.

[0218] Figure 12 is a graph showing how the pressure applied to the pod pump is controlled using variable valves. The vertical axis represents the pressure in the positive and negative tanks (121 and 122 in Figure 11A), respectively, as P R+ and P R- Denote it using P C+ and P C-and represent the positive and negative control pressures acting on the pod pump diaphragm, respectively. As shown in FIG. 12, from time T0 to approximately time T1, a positive pressure is applied to the drive chamber (to force fluid out of the pump chamber). By repeatedly increasing and decreasing the flow restriction by the positive variable valve (117 in FIG. 11A), the pressure applied to the drive chamber is maintained at approximately the desired positive control pressure P C+. 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 determines whether the drive chamber pressure is equal to the desired control pressure P C+. C+ The pressure measurement information is sent to a controller (119 in FIG. 11A) which controls the variable valve so that the pressure changes around the desired control pressure P. In the absence of a fault condition, the diaphragm presses against the solid wall of the pump chamber, thereby ending 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. When the end of stroke is detected, the controller determines that the pressure in the drive chamber has reached the desired control pressure P. C+ The controller closes the variable valve completely so that the pressure does not increase beyond .

[0219] 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 a time shortly after T1 until time T2. As with the exhaust (positive pressure), the stroke described above increases and decreases the flow restriction created by the variable valve until the pressure applied to the drive chamber reaches approximately the desired negative control pressure P C- The pressure can be maintained at a desired control pressure P (less than the negative pressure tank pressure). The pressure varies in a sinusoidal pattern around the desired control pressure. A pressure transducer in the actuation chamber sends pressure measurements to the controller, which controls the variable valve to adjust the actuation chamber pressure to the desired control pressure P C-. If there is no fault condition, the diaphragm will be pulled against the solid wall of the drive chamber, thereby terminating the tension (negative pressure) stroke. As discussed 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 FIG. 12, the end of the tension stroke occurs around time T2. When the end of stroke is detected, the drive chamber vacuum will increase to the desired negative control pressure P C- The controller fully closes the variable valve to prevent the pressure from rising above 0. When the draw stroke is complete, the positive variable valve partially opens, initiating a new discharge stroke with positive pressure.

[0220] 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.

[0221] 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, less wear and tear is caused to the valve, which would otherwise be shortened by repeatedly "hard" opening and closing the two-way valve.

[0222] The end of the stroke is detected when 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 positioned 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).

[0223] 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.

[0224] 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.

[0225] 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 time than necessary. This information can be used for error handling.

[0226] 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.

[0227] 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.

[0228] 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.

[0229] 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.

[0230] To detect subsequent command changes in pod pressure, the pod pressure signal is passed through a cross-correlation filter. 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 command pressure signal is multiplied by the previous sample of actual pressure and added to the previous correlation value. The window is shifted by one frame, and the process is repeated. The resulting signal is then discriminated 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. The absolute value of the output of this filter is passed through a second-order low-pass filter with a frequency equal to the sine wave frequency and a damping ratio of 3.0. This second-order filter is used to combine the discriminated signal and the derived signal and reduce noise in the derived signal. When the two signals are correlated, the value passing through the derived filter is large. When the two signals are uncorrelated (e.g., at the end of a stroke), the value passing through the derived filter is small. The end of stroke can be detected when the filtered cross-correlation signal falls below a predetermined threshold or drops to 1 percent of its maximum value over the stroke. This threshold or percent drop can be varied as a function of pressure and flow rate to tune performance for a given pump scenario.

[0231] Because the end-of-stroke algorithm takes approximately one period of the sine ripple to detect the end of stroke, minimizing this period (maximizing the amplitude of the sine wave) reduces the delay at the end of stroke. Low-pressure, high-pressure flows are not well tracked by the controller. Low-pressure strokes tend to have low fluid velocities, so the end-of-stroke delay is a small percentage of the total stroke time. Therefore, the frequency is low for low-pressure strokes. The frequency of the sine wave can be adjusted as a linear function of the delivery pressure. This ensures the minimum delay when the stroke is shortest. If the frequency of the sine wave for the desired pressure is changed, the filter for the cross-correlation function needs to be further adjusted. The filter is configured to continuously calculate filter coefficients based on this changing frequency.

[0232] The pod chamber pressure is further controlled using two variable solenoid valves. One solenoid valve connects the plenum to a higher pressure source, and the second solenoid valve connects the plenum to a low pressure (or vacuum) sink. Solenoid valves tend to have large neutral zones, so a non-linear offset term is added to the controller to compensate.

[0233] Figure 14 shows an example of a control algorithm. The controller in this example is a standard discrete PI regulator. The output of the PI regulator is split into two paths, one for the source valve and the other to the sink valve. An offset term is added to each of these paths to compensate for the neutral zone of the valve. The resulting command is limited to valves greater than zero (after being inverted in the case of the sink valve).

[0234] The offset terms are negative for the source valve and positive for the sink valve. Thus, both valves actuate even when the error is zero. These offsets improve the trajectory following and disturbance rejection performance of the controller, but also cause both valves to leak at steady state if the command offset is slightly greater than the actual valve neutral zone. In this case, the valves have equal and opposite leakage mass flows at steady state.

[0235] To eliminate this leakage mass flow while the control system is idle, a "power saving" block is added to close the valve if the absolute value of the error term remains small for a predetermined time, similar to using a mechanical brake on a servo motor.

[0236] As shown in Figure 15, the controller in this example uses a standard isolated PI regulator. The circuit for the PI regulator is shown. The integrator can be limited to prevent windup when the command saturates. The integrator is always allowed to unwind. Because the amount of air in the pod is different for the fill stroke and the deliver stroke, the pod response will be very different for the fill stroke and the deliver stroke. The proportional gain is adjusted differently for the deliver stroke and the fill stroke to better adjust for the different pod responses.

[0237] The PI regulator saturation limit should be determined taking into account the resulting offset value. For example, if a valve saturates at 12V and a fixed offset of 5V is added after the PI loop, the PI loop saturation limit should be set to 7V. The different positive and negative saturation limits are due to the different dead bands of the upstream and downstream valves.

[0238] During the fill stroke, the upstream fluid valve is closed and the downstream fluid valve is open, allowing fluid to enter the chamber. During the delivery stroke, the upstream fluid valve is open and the downstream fluid valve is closed, allowing fluid to exit the chamber. Between the end of one stroke and the start of the other stroke, both fluid valves are closed.

[0239] As noted in certain embodiments, the pod pumps can be powered by a control fluid, such as air, nitrogen, water, oil, or the like. The control fluid is selected to be relatively incompressible and, in some cases, relatively inexpensive and / or non-toxic. The control fluid is supplied to the system's pumps using a series of tubes or other suitable conduits. A controller controls the flow of the control fluid within the tubes or conduits. In some embodiments, the control fluid is maintained at different pressures within the tubes or conduits. For example, some of the control fluid is maintained at a positive pressure (i.e., above atmospheric pressure), some at a negative pressure (below atmospheric pressure), or even at zero pressure (i.e., a vacuum). As shown in FIG. 11A, the pod pump is controlled by a control fluid operated by a controller. As previously described, the controller (119) opens and closes valves (e.g., valves 117 and 118) at different times during a pump cycle to expose the pneumatic side of the pod pump to either positive pressure (121) or vacuum (122).

[0240] In more specific embodiments, the controller is isolated from the various fluid circuits (usually electronic) and is not in electrical contact with the fluid circuits, but a controlled fluid (e.g., air) flows between the controller and the various pumps. This configuration has advantages such as ease of maintenance (the controller and the various circuits can be repaired separately). In one embodiment, the fluid circuits are heated to disinfecting temperatures or exposed to relatively high temperatures or harsh conditions (e.g., radiation) effective for disinfection, while the controller is kept isolated from the harsh conditions by an insulating barrier (e.g., a "firewall") or the like.

[0241] Thus, in one embodiment, the system has a "cold" section (unheated) and a "hot" section that is partially heated for disinfection. The "cold" section is insulated from the "hot" section by insulating material. In one embodiment, the insulation can be formed by molding a foam material, but the insulation can also be formed by spraying, or even by cutting a sheet material.

[0242] In one embodiment, the "hot" section is heated to a relatively high temperature. For example, the "hot" section is heated to a temperature sufficient to sterilize the components within the "hot" section. Because many electronic components degrade in other ways when heated above 50°C, it is beneficial to separate the electronic components from other components being sterilized. Thus, components that may occasionally need to be sterilized are kept in the "hot" section, while components that cannot be heated to such temperatures are kept in the "cold" section. In one embodiment, the "cold" section includes a circulation system, such as a fan or grid, that allows air to flow in and out of the cold box.

[0243] The "hot" section may be fully or partially covered with insulation. In some embodiments, the insulation extends to cover access points to the "hot" section, such as doors, ports, gaskets, etc. For example, when the "hot" section is sealed, the insulation completely covers the "hot" section.

[0244] Examples of components that are within the "cold" section include power supplies, electronic components, power lines, air control components, etc. In some embodiments, at least some of the fluids entering or leaving the "hot" section pass through the "cold" section, although in other embodiments, fluids pass only through the "hot" section without passing through the "cold" section.

[0245] Examples of components within the "hot" section include cassettes, fluid lines, etc. In some embodiments, several electrical components are located in the "hot" section. These include a heater, which heats the hot box itself in addition to the fluid (see heater 72 in FIG. 3A). In other embodiments, the heater heats the entire "hot" section to the desired temperature.

[0246] In one embodiment, the "hot" section includes some or all of the fluid lines. Additionally, the "hot" section may include temperature sensors, conductivity sensors, blood leak sensors, heaters, other sensors, switches, emergency lights, etc.

[0247] In some embodiments, the manifold for air or other control fluid is moved from the "cold" section to the "hot" section. Separating components into "hot" and "cold" sections has several benefits, including the service life, reliability, or efficiency of use of electrical components. For example, by separating components into "hot" and "cold" sections, the entire hot box is heated. This allows for more efficient use of heat resulting in a more energy efficient system. This also allows for the use of standard, off-the-shelf electronic components resulting in lower costs.

[0248] In some embodiments, the control fluid used to control the pumps, valves, etc. is air, which is introduced into the system by operation of one or more air compressors. In some embodiments, the air compressors are kept separate from the blood and dialysate flow paths within the system, and air from the air compressors is introduced to the pumps via multiple lines. For example, in one embodiment, an air interface is used to introduce air from the air compressor into lines leading to the various pumps and chambers.

[0249] FIG. 16 shows a schematic diagram of a dual-housing configuration in one embodiment. This configuration is useful for cassettes containing multiple pneumatically operated pumps and valves. As the number of pumps and valves in a cassette increases significantly, the cassette containing these pumps and valves becomes larger, and the pressures associated with these pumps and valves increase, making it difficult to properly seal and position all of the pumps and valves. This difficulty can be alleviated by using two or more separate housings. The valves and pumps (pod pump 42) are housed in a main housing 41, which has connecting tubes 45 extending from pneumatic ports 44. The main housing 41 also includes inlet and outlet tubes 43, which allow fluid to flow in and out of the main housing. The connecting tubes 45 connect the pumps and valves within the main housing 41 and a small, secondary tube-holding housing 46. The tube-holding housing 46 provides air interfaces for each tube. It is easier to properly position and seal each air interface to the base unit of the vessel on the small tube-holding housing 46 than directly on the large main housing 42.

[0250] In some embodiments, the control fluid (e.g., air) is supplied to the system with one or more supply tanks or other pressure sources. For example, if two tanks are used, one supply tank is a positive pressure tank with a setpoint of 750 mmHg (gauge pressure) (approximately 100 kPa, where 1 mmHg is approximately 133.3 Pascals), and the other supply tank is a negative pressure, or vacuum, tank with a setpoint of 450 mmHg (gauge pressure) (approximately 60 kPa). This pressure differential is used to allow precise control of the variable valve on the pod pump between the supply tank and the required pod pressure. The supply pressure limit can be set based on a pressure differential sufficient to control the variable valve and the maximum pressure that can be set for the patient's blood flow pump. Thus, two tanks are used to supply pressure and control the fluid for the entire system.

[0251] In one embodiment, two independent compressors supply fluid to a supply tank. For example, the tank pressures may be controlled using any suitable technique, such as a simple bang-bang controller (a controller with an open and a closed state) or a sophisticated control mechanism. In one example of a bang-bang controller for a positive pressure tank, the compressor servicing the positive pressure tank will start if the actual pressure is the desired pressure minus hysteresis. If the actual pressure is the desired pressure plus hysteresis, the compressor servicing the positive pressure tank will stop. The same logic applies to a vacuum tank and vacuum compressor, but with the hysteresis reversed. If the pressure tank is not regulated, the compressor will stop and the valve will close.

[0252] Reducing the size of the hysteresis band allows for more precise control of the pressure tanks. However, this requires increasing the compressor operating cycle. If very precise control of these tanks is required, the bang-bang controller can be replaced by a PID controller and the compressor can use a PWM signal. Other control methods are also possible.

[0253] However, in other embodiments, other pressure sources are used, such as multiple positive pressure sources and multiple negative pressure sources. For example, to minimize leakage, multiple positive pressure sources are used, providing different positive pressures (e.g., 1000 mmHg and 700 mmHg) (approximately 133.3 kPa and 93.3 kPa). The negative pressure is -400 mmHg (approximately -53.3 kPa). In one embodiment, the negative pressure source is a vacuum pump and the positive pressure source is an air compressor.

[0254] Certain aspects of the present invention include various sensors. For example, various embodiments of the invention disclose systems and methods for fluid processing using a sensor instrument system comprising a sensor manifold. Such embodiments relate to systems and methods for diagnosing, treating, or improving various medical conditions. These inventions, by way of example, include systems and methods for delivering, measuring, controlling, and / or analyzing various types of biochemical fluids and therapeutic agents, such as dialysis fluids, and various forms of extracorporeal treatment and therapy. Further examples include water treatment systems, water distillation systems, and fluid-utilizing systems, including systems for diagnosing, treating, and improving fluids such as dialysis fluids.

[0255] Examples of embodiments of the inventions described herein include dialysis systems and methods, and more particularly, examples of embodiments of the inventions described herein include the hemodialysis systems and methods described in U.S. patent application Ser. No. 11 / 871,680, filed Oct. 12, 2007, entitled "Pump Cassette," or the commonly assigned U.S. patent application Ser. No. 11 / 871,680, filed Oct. 12, 2007, entitled "Apparatus Integrated with Cassette System."

[0256] In such systems and methods, one or more sensor manifolds are used so that media is moved from one environment to another, more conductive environment for sensor readings. For example, a cassette manifold is maintained in an area that is not affected by conditions such as temperature and humidity that are undesirable for sensor instruments, such as sensor probes, depending on various environmental conditions. Furthermore, sensor instruments and sensor systems are sensitive and more prone to malfunction than other components of the system. Using a sensor manifold to isolate the sensor instruments and sensor instrument systems from other components of the system reduces the impact of the sensor instruments and systems on other components during inspection, measurement, repair, or replacement. Inspection, measurement, repair, or replacement of a sensor manifold with minimal impact on other components of the system may be advantageously used in conjunction with a commonly-filed U.S. patent application entitled "Instrument Integrated with Cassette System." The sensor manifold is replaced somewhat more frequently than other components of the system.

[0257] Figures 53-58 illustrate various embodiments of a sensor manifold. In these embodiments, one or more fluidic media are contained within cassette manifold 4100. For example, media enters cassette manifold 4100 through connector 4101 and exits cassette manifold 4100 through connector 4102. A flow path through the cassette is formed between connectors 4101 and 4102 (shown as flow path 4225 in Figure 54). Similarly, flow paths extend between connectors 4103 and 4104; 4105 and 4106; 4107; 4108 and 4109; 4110 and 4111; and 4112 and 4113 (shown as flow paths 4223, 4220, 4222, 4224, and 4221, respectively, in Figure 54). In certain embodiments, each flow path contains media having different characteristics. In other embodiments, one or more flow paths contain the same or similar media. In certain embodiments, the same medium is flowed through multiple flow paths simultaneously to check and / or calibrate the instrumentation system of sensors associated with such flow paths.

[0258] Referring to FIG. 55, a sensor manifold 4100 for use with the sensor instruments and sensor instrument systems is shown. The cassette includes a top plate 4302 and a base 4301. A flow channel 4225 extending between the connectors 4101 and 4102 extends between the base and the top plate. The cassette can be constructed from a variety of materials. Typically, the materials used are rigid and inflexible. In a preferred embodiment, the cassette is formed from polysulfone, although in other embodiments, the cassette is formed from other rigid or thermoplastic materials. Some embodiments of the sensor manifold 4100 can be manufactured using the systems and methods disclosed in the commonly assigned U.S. patent application, entitled "Instrument Integrated with Cassette System," filed on even date herewith.

[0259] Referring again to FIG. 55, the sensor manifold 4100 used with the sensor instrument and sensor instrument system includes a printed circuit board 4304 (PCB) and a PCB cover 4305. Various embodiments include a connector 4303 (also shown in FIGS. 53 and 56B) that mechanically couples the cassette manifold 4100 to a system, such as a hemodialysis system. The cassette manifold 4100 employs various methods to hold the layers of the sensor manifold 4100 together. Various embodiments employ screws, such as 4306 (also shown in FIG. 56B), as shown in FIG. 43, screws used in other embodiments, welding, clips, clamps, and other chemical and mechanical joining methods.

[0260] FIG. 56A shows an exemplary embodiment of a sensor manifold 4100. Connector 4401 is used to introduce or remove media from flow path 4402. Sensor probes 4404 extending into flow path 4402 are incorporated into sensor manifold 4100 to determine properties of media flowing through a particular flow path of the sensor manifold. In one embodiment, a sensor probe is used to sense the temperature or other property of the media. In another embodiment, a sensor probe is used to detect the temperature, conductivity, or other property of the media. In further embodiments, three or more sensor probes are used. In some embodiments, one or more combination probes for sensing temperature and conductivity are utilized. In other embodiments, the conductivity sensor and temperature detector may be a conventional conductivity sensor or temperature detector. In one embodiment, the conductivity sensor element (or sensor lead) is a graphite post. In other embodiments, the conductivity sensor element is formed from stainless steel, titanium, or any other material commonly used for measuring post conductivity. In certain embodiments, the conductivity sensor includes a sensor mechanism and electrical connections that transmit a signal from the sensor to a controller or other device. In various embodiments, the temperature detector may be a temperature detector typically used (or capable of being used) for temperature detection.

[0261] Referring to FIG. 56A, the sensor probe 4404 is electrically connected to a PCB 4405. In one specific embodiment, an electrically conductive epoxy is utilized between the sensor element 4404 and the PCB 4405, although any suitable electrical connection method known in the art may be used to ensure proper electrical connection. The PCB 4405 is represented by an edge connector 4406. In various embodiments, the edge connector 4406 is used to transmit sensor information from the cassette manifold 4100 to the main system. The edge connector 4406 is coupled to a media edge connector (such as media edge connector 4601 shown in FIG. 58). In various embodiments, the media edge connector 4601 is attached to the hemodialysis machine (not shown). In such embodiments, guide tracks 4310 and 4311 (as shown in FIG. 55) are utilized to coordinate the relationship between the edge connector 4406 and the media edge connector 4601. Various embodiments also include a connector 4303 (as shown in Figures 53, 55 and 56B) for mechanically coupling the cassette manifold 4100 to a system such as a hemodialysis system.

[0262] FIG. 56A shows an air trap 4410. In certain embodiments, the air trap 4410 is utilized to capture and clear air from the system. In particular, as shown in FIG. 54, media flows through a flow path 4222 between connectors 4107 and 4109 of the sensor manifold 4100. As the media flow slows around the turn of the flow path 4222 (near connector 4108), air is removed from the following media at connector 4108.

[0263] 56B, PCB cover 4305 is shown. PCB cover 4305 is coupled to sensor manifold 4100 by connector 4306. Edge connector 4406 is also shown.

[0264] According to certain embodiments, the sensor manifold 4100 is passive with respect to flow control. In such embodiments, the sensor manifold 4100 does not include a valve or pumping mechanism to control the flow of media. In such embodiments, the flow of media is controlled by the external surface of a fluid control device to the sensor manifold 4100. In other embodiments, the sensor manifold includes one or more known mechanical valves, pneumatic valves, or other types. In such embodiments, the sensor manifold includes one or more pumping mechanisms, including pneumatic pumping mechanisms, mechanical pumping mechanisms, or other types of known pumping mechanisms. Examples of such valves and pumping mechanisms include the valves and pumping mechanisms described in U.S. patent application Ser. No. 11 / 871,680, filed Oct. 12, 2007, entitled "Pump Cassette," or the U.S. patent application filed on even date herewith, entitled "Apparatus Integrated With Cassette System." 57 shows the base 4301 of the connector 4401. The top plate 4302 is shown along with the connector 4303. The sensor probe 4501 extends through the top plate 4302 into the flow channel 4503. The sensor probe 4501 may be any of a variety of forms, including those sensor probes described herein.

[0265] The sensing probes, such as sensing probe 4501, can all be the same, can be individually selected from a variety of sensors based on the type of function to be performed, or the same probe can be individually modified based on the type of function to be performed. Similarly, the configuration of the flow path, such as the length and shape of the flow path, can be selected based on the function to be performed. As an example, a temperature sensor, such as a thermistor, can be used to detect the temperature of the target medium within the flow path. Also, as an example, to measure the conductivity of the target medium, one sensing probe configured to measure temperature and conductivity and one sensing probe configured to measure only conductivity can be used. In other embodiments, two or more sensing probes configured to measure both temperature and conductivity can be used. In various embodiments of such a configuration, for example, a second temperature sensor can be present that is not used during normal operation, or a second temperature can be used for redundant temperature measurements, or a second temperature can be used for redundant temperature measurements.

[0266] Referring again to FIG. 57, PCB 4502 is shown with electrical connections 4503. As further shown in FIG. 58, PCB 4602 is shown with electrical connections 4603 for connection to the sensing probe (shown as 4501 in FIG. 45). PCB 4602 also includes openings 4604 for attachment to the top plate (shown as 4305 in FIG. 57). In certain embodiments, electrical connections 4603 may be attached to or fabricated with PCB 4602 with air gap 4606. In such embodiments, air gap 4606 may be utilized to provide protection for the electrical connections between sensing probe 4501 and PCB 4602 by allowing the various components of sensor manifold 4100 to contract and expand with less impact relative to PCB 4602.

[0267] 58, PCB 4602 is also shown with edge connector 4605. As described herein, edge connector 4605 can interface with edge connector receiver 4601, which can be coupled to a system, such as a hemodialysis system, that interfaces with sensor manifold 4100.

[0268] Various embodiments of the exemplary sensor manifold 4100 shown in Figures 53-58 can be used in combination with the hemodialysis systems and methods described in U.S. patent application Ser. No. 11 / 871,680, filed Oct. 12, 2007, and entitled "Pumping Cassette" (Attorney Docket No. DEKA-019XX), or the hemodialysis systems and methods described in concurrently filed U.S. patent application Ser. No. 11 / 871,680, entitled "Cassette System Integrated Apparatus" (Attorney Docket No. F62). In one particular embodiment, the sensor manifold 4100 includes all of the temperature and conductivity sensors shown in Figure 59. Figure 59 shows a fluidics design according to one embodiment of the invention described in the above-referenced patent application.

[0269] As an example, in various embodiments, the temperature and conductivity of the target media at position 4701, as shown in FIG. 59, can be measured using sensor manifold 4100. In such embodiments, the target media flows via flow path 4220 (as shown in FIG. 54) to tubing connector 4105 (as shown in FIG. 53) and exits at tubing connector 4106 (as shown in FIG. 53). The conductivity of the target media is measured by two sensing probes (not shown) extending into flow path 4220, at least one of which is configured to include a temperature-sensing element, such as a thermistor. The conductivity and temperature measurements of the target media can be used to determine and / or correlate various information of utility to the hemodialysis system. For example, in various embodiments at position 4701 in FIG. 59, the target media consists of water to which a bicarbonate-based solution has been added. The conductivity of the target media at position 4701 can be used to determine whether an appropriate amount of bicarbonate-based solution was added prior to position 4701. In certain embodiments, if the conductivity measurement falls outside a predetermined range or deviates from the predetermined measurement by more than a predetermined amount, the subject medium may not contain an appropriate concentration of bicarbonate-based solution. In such instances, in certain embodiments, the hemodialysis system receives an alert.

[0270] Also, by way of example, in various embodiments, the conductivity of the target medium at location 4702, as shown in FIG. 59, can be measured using sensor manifold 4100. In such embodiments, the target medium flows via flow path 4221 (as shown in FIG. 54) to tubing connector 4112 (as shown in FIG. 41) and exits at tubing connector 4113 (as shown in FIG. 53). The conductivity of the target medium is measured by two sensing probes (not shown) extending into flow path 4221, at least one of which is configured to include a temperature-sensing element, such as a thermistor. The conductivity and temperature measurements of the target medium can be used to determine and / or correlate various information of utility to the hemodialysis system. For example, in various embodiments at location 4702 of FIG. 59, the target medium consists of water to which a bicarbonate-based solution is added, followed by an acid-based solution. The conductivity of the target medium at location 4702 is used to determine whether the appropriate amount of acid-based solution (and bicarbonate-based solution in the previous step) was added before location 4702. In certain embodiments, if the conductivity measurement falls outside a predetermined range or deviates from the predetermined measurement by more than a predetermined amount, the target medium may not contain the appropriate concentrations of acid-based solution and bicarbonate-based solution. In such an instance, in certain embodiments, the hemodialysis system receives an alert.

[0271] As a further example, in various embodiments, the temperature and conductivity of the target media at location 4703 can be measured using sensor manifold 4100, as shown in FIG. 59. In such embodiments, the target media flows into and out of tubing connector 4107 (as shown in FIG. 53) via flow path 4222 (as shown in FIG. 54) and into and out of tubing connector 4109 (as shown in FIG. 53). As described herein, air can be removed from the target media by circumventing a bend in flow path 4222. In such an example, a portion of the target media is removed to drain via tubing connector 4108, expelling the air from the void space along with the target media. The conductivity of the target media is measured by two sensing probes (not shown) extending into flow path 4222, at least one of which is configured to include a temperature-sensing element, such as a thermistor. Measurements of the conductivity and temperature of the target media can be used to determine and / or correlate various information of utility to the hemodialysis system. For example, in various embodiments, the conductivity measurement at location 4703 in Figure 59 can be used to correlate with the clearance rate of the dialysis machine. In such instances, in certain embodiments, this information is then sent to the hemodialysis system.

[0272] As a further example, in various embodiments, the temperature of the target media at location 4704 can be measured using sensor manifold 4100, as shown in FIG. 59. In such embodiments, the target media flows via flow path 4223 (as shown in FIG. 54) to tubing connector 4103 (as shown in FIG. 53) and exits at tubing connector 4104 (as shown in FIG. 53). The temperature of the target media is measured by one or more sensing probes (not shown) extending into flow path 4223. Measuring the temperature of the target media at location 4704 can be used to determine and / or correlate various information of utility to the hemodialysis system. For example, in various embodiments at location 4704 in FIG. 59, the temperature of the target media is determined downstream of heating device 4706. If the temperature deviates from a predetermined range or deviates from a predetermined measurement by more than a predetermined amount, the hemodialysis system receives an alert. For example, in one embodiment, the target media can be recirculated through heating device 4706 until the temperature of the target media is within a predetermined range.

[0273] As a further example, in various embodiments, the temperature and conductivity of the target media at location 4705 can be measured using sensor manifold 4100, as shown in FIG. 59. In such an embodiment, the target media flows via flow path 4224 (as shown in FIG. 54) to tubing connector 4110 (as shown in FIG. 53) and exits at tubing connector 4111 (as shown in FIG. 53). The conductivity of the target media is measured by two sensing probes (not shown) extending into flow path 4224, at least one of which is configured to include a temperature-sensing element such as a thermistor. The conductivity measurement or temperature measurement of the target media can be used to determine and / or correlate various information of utility to the hemodialysis system. For example, the temperature and conductivity measurement at location 4705 can be used as an additional safety check to determine whether the temperature, conductivity, and their correlation, composition of the target media are within acceptable ranges before the target media reaches dialysis machine 4707 and, therefore, the patient. In certain embodiments, if the temperature and / or conductivity measurements fall outside a predetermined range or deviate from the predetermined measurement by more than a predetermined amount, the hemodialysis system receives an alert.

[0274] For various embodiments described herein, the cassette can be formed from any material, including plastic and metal. The plastic can be flexible, rigid, semi-flexible, semi-rigid, or any combination thereof. In some of these embodiments, the cassette includes one or more thermal wells. In some embodiments, one or more sensing probes and / or one or more other devices for transferring information about one or more characteristics of such target media are in direct contact with the target media. In some embodiments, the cassette is designed to hold a fluid having a flow rate or pressure. In other embodiments, one or more compartments of the cassette are designed to hold a largely stagnant media or media trapped in a conduit, even when the media is flowing.

[0275] In some embodiments, the sensor device may be used based on the need to separate the target medium from the sensing probe, however, in other embodiments, the sensing probe may be used for temperature, conductivity, and / or other detection directly with the target medium.

[0276] Another aspect of the invention relates generally to the methods and operation of systems, such as hemodialysis systems, that are primed, flow balanced, emptied, purged with air, disinfected, etc., as discussed herein.

[0277] One set of embodiments relates to priming a system with fluid. The fluid to be primed is first introduced into a dialysate tank (e.g., dialysate tank 169). Next, the ultrafilter 73 is first primed by pushing fluid from the dialysate tank 169 to ultrafilter 73 and then out to drain through line 731 via waste line 39, as shown by the bold black line in FIG. 17A. Any air present in the ultrafilter 73 naturally rises to the prime port and is flushed to drain.

[0278] Next, as shown in Figure 17B, the balancing circuit and its pump 159 are primed by pushing fluid through the ultrafilter 73, through the balancing circuit, and out to drain. The pump 159 is primed by forcing fluid upward (through the ultrafilter to drain). Air entering the dialyzer 14 is bubbled to the top of the dialyzer and out the outlet of the dialyzer to drain.

[0279] The blood flow pump and tubing are then primed by circulating fluid through the blood flow circuit and air trap and back to the directing circuit via conduit 67. As seen in FIG. 17C, the fluid passes through the ultrafilter and dialyzer, forcing the fluid through the air trap and down to drain. The air trap traps any air circulating in the blood flow circuit and sends it to drain. Priming can be stopped when the air sensor stops detecting air (and some additional fluid is allowed to flow through the system as a safety margin).

[0280] Another set of embodiments relates to adding air to the system, e.g., emptying various fluids in the system. For example, in one operation, the dialysate tank is emptied. The outlet 226 of the dialysate tank 169 is opened and the pump 159 is used to pump fluid from the dialysate tank to drain until air is detected by the pump 159 (discussed later). This is shown in FIG.

[0281] Air is also pumped into the balancing circuit in certain embodiments. This is shown in FIG. 20. The dialysate 16 outlet 226 is opened to allow air into the dialysate tank. Using pump 159, air is pumped through the outside of the ultrafilter 73. This air pressure moves fluid outside the ultrafilter inward, forcing it through the dialyzer and down to drain. During this operation, the pump 159 and the outside of the ultrafilter will fill with air.

[0282] Additionally, air is introduced into the blood flow circuit through the anticoagulant pump 80, as shown in Figure 21A. First, the air is introduced into the pod pump 23 (Figure 21A), from which it is directed either into the arterial line 203 and down to drain (Figure 21B) or into the venous line 204 (through the dialyzer 14) and down to drain (Figure 21C).

[0283] In one set of embodiments, an integrity test is performed. Because the ultrafilter and dialyzer are constructed using membrane materials that do not easily allow air to pass through when wet, an integrity test can be performed by priming the filter with water and then applying compressed air to one side of the filter. In one embodiment, an air outlet is included in one of the blood flow pumps, so the pump chamber can be used to pump air for use in the integrity test. This embodiment takes advantage of the larger pump. The air pressure forces all the water through the filter, stopping the air flow as soon as the water is replaced. However, if air flow continues, the membrane will rupture and need to be replaced. Therefore, the system is primed with water. First, the mixing circuit is primed to remove any air prior to the dialysate tank. Then, the outside of the ultrafilter is primed next, since it is believed that the ultrafilter will not pass water to the balancing circuit until the outside is primed. The balancing circuit and dialyzer are then primed. Finally, water is passed over the dialyzer to prime the blood flow circuit.

[0284] The mixing circuit is primed by first pushing water using pump 183, through line 281 and bicarbonate source 28, and into dialysate tank 169 via each of the pumps and line 186. The dialysate tank 169 is vented by pushing air bubbles upward and expelling such air via outlet 226. Once air is primed from the dialysate tank 169, the tank fills with water, and the priming flow continues from the dialysate tank through ultrafilter 73 to drain. This is seen in FIG. 22A. Next, water is primed as previously described (see FIG. 17). Next, the blood flow pod pump 23 is filled with water from the dialysate tank 169, as shown in FIG. 22B, while the balance pump 15 is emptied, as shown in FIG. 22C.

[0285] Testing is performed by using a blood flow pump to push each chamber of water past the dialyzer 14 to the balance pump chamber 15. The balance pump chamber starts empty (FIG. 22C) and is vented to atmosphere so that it is at atmospheric pressure on the dialysate side of the dialyzer 14. See FIG. 22D. Each of the blood flow circuit chambers delivers using a specific pressure, and the end of the stroke is measured to determine the flow rate.

[0286] Another integrity test is the ultrafilter flow test, in which the dialysate tank is filled with water, the ultrafilter is primed by pumping water from the dialysate tank through the ultrafilter into line 731, and water is pumped through the ultrafilter to control the flow rate and monitor the delivery pressure needed to maintain flow.

[0287] Another set of embodiments relates to disinfecting and cleaning the system. This process removes any material that accumulates during treatment and kills any active pathogens. In some instances, disinfectants are used, but typically heat is used. A dialysate tank is used to maintain the water, which is drained and replenished as needed.

[0288] The recirculation flow path is shown in FIG. 23. Flow along this path is essentially continuous, with conduit 67 connecting the blood flow circuit and the direction circuit. The main flow path is heated using heater 72, which is used to raise the temperature of the water in the recirculation flow path, e.g., to a temperature sufficient to kill any active pathogens that may be present. Some of the water flows to drain, but most is recirculated. Note that in this example, lines 48 and 731 are kept open to ensure proper disinfection. Additionally, a flow path through ultrafilter 73 is periodically selected to remove air from the ultrafilter and / or provide recirculation flow through the same path. Temperature sensors (e.g., sensors 251 and 252) may be used to ensure proper temperature adjustment. Non-limiting examples of such sensors are described in concurrently filed U.S. patent application entitled "Sensor Apparatus Systems, Devices and Methods" (Attorney Docket No. F63, now Application No. 12 / 038,474), which is incorporated herein by reference.

[0289] In one set of embodiments, the system is primed with dialysate as follows: In this operation, the pod pump 280 is filled with water (FIG. 24A), and then the water is pushed backward by the pump 183, expelling air from the top of the bicarbonate source 28. The air is collected in the pod pump 282. See FIG. 24B. The air in the pod pump 282 is then expelled through the pod pump 280 and line 186 to the dialysate tank 169. The outlet 226 of the dialysate tank 169 is left open to allow the air to be expelled from the system (FIG. 24C). Additionally, acid is pumped from the acid source 29. It is then mixed with the bicarbonate concentrate and water from the bicarbonate source 28. As shown in FIG. 24D, the pump 183 is used to provide sufficient water pressure to fill the bicarbonate source 28 with water.

[0290] The acid and bicarbonate solutions (and sodium chloride solution, if a separate sodium chloride source is present) are then metered with the incoming water to prepare the dialysate. Sensors 178 and 179 are used to ensure that the partial mixture of each component with the water is accurate. Dialysate that does not meet specifications is diverted to drain, while good dialysate is pumped into the dialysate tank 14.

[0291] In another set of embodiments, the anticoagulant pump is primed. Priming the pump removes air from the heparin pump and fluid path and ensures acceptable pressure within the anticoagulant vial. The anticoagulant pump can be designed so that air in the pump chamber flows into the vial. Testing is performed by closing all of the anticoagulant pump's fluid valves, measuring the outside volume, applying vacuum to the fluid management system chamber, opening the valves to draw fluid from the vial into the pump chamber, measuring the outside volume (again), applying pressure to the fluid management system chamber, opening the valves to draw fluid back into the vial, and 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 fill from the vial, the vial pressure is too low and air needs to be introduced. Conversely, if the pump chamber cannot flow into the vial, the vial pressure is too high and some anticoagulant needs to be pumped out of the vial. The anticoagulant drawn from the vial during this test can be discarded, for example, via a drain.

[0292] In yet another set of embodiments, while not connected to a patient, the system is flushed with dialysate. This can be done before or after treatment. Before treatment, the dialysate is diverted, with a portion sent to drain, to avoid the buildup of sterilant in the dialysate. After treatment, this operation flushes the blood flow path with dialysate, pushing any remaining blood to drain. The flow paths used in this operation are similar to those used with water, as previously described.

[0293] The acid concentrate can be pumped from the mixing chamber. Pump 184 is activated, causing pod pump 280 to pump the acid from pump 184 and acid source 29, which are mixed in line 186 and sent to drain. Similarly, as shown in FIG. 25, bicarbonate can be pumped from the mixing chamber. Pump 183 is used to introduce water from bicarbonate source 28, and pod pump 280 is then used to pass the water through line 186 to drain.

[0294] In yet another set of embodiments, dialysate prime is removed from the blood flow circuit, avoiding the need to provide priming fluid to the patient. Figures 26A and 26B show fluid flowing out of each of the balance pump chambers and to drain. Next, the dialysate side of the dialyzer 14 is closed, while blood is introduced into the blood flow path from the patient (Figure 26C). Next, the patient connections are closed, while the blood flow pump chamber 23 pushes priming fluid past the dialyzer and into the balance circuit (Figures 26D and 26E). This fluid is then pushed to drain as previously described. This operation is repeated as necessary until the priming fluid is sufficiently removed. The balance pump is then refilled with fresh dialysate, and the patient connections are maintained closed, as shown in Figure 26F.

[0295] In yet another set of embodiments, a bolus of anticoagulant can be delivered to a patient. First, as shown in FIG. 27A, a bolus of anticoagulant is pumped from a vial (or other anticoagulant source) into one chamber of pump 13. The anticoagulant pump alternates between pumping air into the vial and pumping anticoagulant out of the vial, thereby maintaining a relatively constant pressure. The remaining volume is then filled with dialysate (FIG. 27B). The combined fluid is then delivered to the patient down arterial line 203, as shown in FIG. 27B. In some instances, the same pump chamber is again filled with dialysate (see FIG. 27B), and that volume is delivered to the patient, ensuring all of the anticoagulant has been properly delivered.

[0296] In yet another embodiment, the system can perform push-pull hemodiafiltration. In such cases, the blood flow pump 13 and balance pump 15 can be synchronized to move fluid back and forth across the dialyzer. In hemodiafiltration, hydrostatic pressure is used to drive water and solutes through the dialyzer membrane from the blood flow circuit to the balance circuit, where they are discharged. Without being bound by theory, it is believed that larger solutes are more easily transported into the dialysate used by convective forces in hemodiafiltration.

[0297] In one set of embodiments, the infusion of a solution is used to deliver fluid to the patient. As shown in Figure 28, a directing circuit pump 159 is used to push fluid from the dialyzer 14 into the blood flow circuit, thereby delivering fluid (e.g., dialysate) to the patient.

[0298] According to another set of examples, after repeated use, a dialyzer may lose its efficiency and ability to function altogether due to compounds adhering to and accumulating on the membrane walls of the dialyzer. Any reference measurement may be used to determine the clearance rate of the dialyzer. However, one method for determining how much the dialyzer is loaded, i.e., how much the clearance rate of the dialyzer has decreased, is to push gas into the blood side of the dialyzer while retaining liquid on the dialysate side of the dialyzer. By measuring the volume of gas in the dialyzer, the clearance rate of the dialyzer can be determined based on the measured volume of gas in the dialyzer.

[0299] Alternatively, in another embodiment, the air pressure of the system of the present invention may determine the cleaning rate as follows: By creating a pressure differential across the dialysis machine and measuring the fluid velocity of the dialysis machine, the cleaning rate of the dialysis machine is correlated / measured or calculated based on the pressure differential and the fluid velocity. This may be done based on known correlations or pre-programmed criteria, including, for example, correlation tables, i.e., mathematical relationships. For example, a look-up table may be used, or a determined mathematical relationship may be used.

[0300] The clearance rate of the dialyzer can also be measured using a conductivity probe in the blood tubing plug-back recirculation path. After treatment, the patient is connected to the blood tubing returning to the disinfection port. The fluid in the blood tubing and dialyzer is recirculated through these disinfection port connections, and the conductivity of this solution can be measured as it passes through a conductivity measurement cell in this recirculation path.

[0301] To measure the cleaning rate of a dialyzer, pure water may be circulated through the dialysate pathway and the conductivity of the fluid flowing through the blood recirculation pathway is continuously monitored. The pure water removes ions from the solution in the blood flow circuit recirculation pathway at a rate proportional to the cleaning rate of the dialyzer. The cleaning rate of a dialyzer can be determined by measuring the rate at which the conductivity of the solution in the blood flow circuit recirculation pathway changes.

[0302] The cleaning rate of the dialyzer can be measured by circulating pure water on the one hand and dialysate on the other hand and measuring the amount of fluid passing through the dialyzer using conductivity. In one set of embodiments, it is desirable to return as much blood as possible to the patient during a power outage. Because one embodiment of a hemodialysis system uses compressed gas to power the various pumps and valves used, other embodiments can utilize such compressed gas to return blood from the system to the patient during a power outage. Following this method and referring to FIG. 29A, dialysate is pumped across the dialyzer 14 to cleanse the blood in the blood flow circuit 19 and return it to the patient. Compressed air is used to pump dialysate into the dialyzer 14. Valve 77 releases the compressed air to activate this function. This method can be used when a power outage or other disturbance prevents the dialysis machine from cleaning and returning the patient's blood in the manner that it normally does at the end of treatment.

[0303] Compressed air is used to increase the pressure on the dialysate side of the dialyzer 14, forcing the dialysate from within the dialyzer to the blood side, which forces the patient's blood back into the patient's body. The patient or an assistant monitors the treatment and secures the tubing between the blood flow circuit and the patient once adequately purified blood is returned.

[0304] In one embodiment, a tank 70 is incorporated into the hemodialysis system and filled with compressed air before treatment begins. The tank 70 is connected to the dialysate circuit 20 via a manually actuated valve 77. When treatment is completed or interrupted, the valve 77 is opened by the patient or an assistant to initiate the cleanse-return procedure. The membrane of the dialyzer 14 allows the passage of dialysate but not air. The compressed air moves the dialysate until the patient-side tubing is secured or the dialysate side of the dialyzer is filled with air.

[0305] In another embodiment, a tank containing compressed air is provided as an accessory to the dialysis machine. This tank is attached to the dialysate circuit of the machine to initiate the clean-up procedure if the procedure is stopped prematurely due to a power failure or system failure of the machine. As in the previous embodiment, the clean-up procedure ends when the patient-side tubing is secured or the dialysate side of the machine fills with air.

[0306] In another embodiment, shown in FIG. 29B, an air tank 70 is integrated into the system and attached to a fluid tank 75 with a flexible diaphragm 76 that separates the air from the dialysate. In this case, rather than forcing compressed air into the dialysate circuit 20, the compressed air presses against the diaphragm 76, increasing the pressure in the dialysate circuit 20. The amount of dialysate that can be moved is determined by the volume of the fluid chamber 75. The cleanse-return procedure ends when the patient tubing is secured or when all the fluid has been drained and the diaphragm 76 bottoms out against the wall of the fluid chamber 75.

[0307] In any of these embodiments, the operation of the system or method is periodically tested by running a dialysate machine program between treatments. During testing, the user interface prompts the user to perform a cleanse-return treatment, and the machine monitors the dialysate circuit pressure to ensure proper operation.

[0308] 29A and 29B, blood is drawn from the patient by blood flow pump 13, pumped through dialyzer 14, and returned to the patient. These components and the tubing connecting them constitute blood flow circuit 10. The blood contained in blood flow circuit 10 must be returned to the patient when treatment is completed or interrupted.

[0309] Dialysate is drawn from the dialysate tank 169 by the dialysate pump 159 and passed through the heater 72 where it is heated to body temperature. The dialysate then flows through the ultrafilter 73, which removes pathogens and pyrogens that may be present in the dialysate. The dialysate then flows through the dialyzer to provide therapy and is returned to the dialysate tank.

[0310] The bypass valve 74 can also be used to isolate the dialyzer 14 from the rest of the dialyzer circuit 20. To isolate the dialyzer 14, two valves connecting the dialysate circuit 20 to the dialyzer are closed and one valve is opened to shunt dialysate around the dialyzer.

[0311] This cleanse-return procedure can be used whether the dialyzer 14 is isolated or not, and is used when the procedure is completed or interrupted. When the dialysate machine is turned off and stopped, the pump does not run. When the patient is ready for the cleanse-return procedure, the air valve 77 is opened by the patient or an assistant. Air from the compressed air tank 70 flows into the dialysate circuit 20, increasing the pressure on the dialysate side of the dialyzer 14. This increase in pressure can be achieved by allowing air to enter the dialysate circuit directly, as shown in FIG. 29A, or indirectly by pressing on a septum 76, as shown in FIG. 29B.

[0312] Air pressure on the dialysate side of the dialyzer causes a portion of the dialysate to flow from the dialyzer 14 into the blood flow circuit. This dialysate displaces the blood, purifying it and returning it to the patient. The patient or assistant can observe the purification process by keeping an eye on the dialyzer 14 and the blood tubing. The dialysate starts in the dialyzer, displacing the blood and making it cleaner. This cleaner solution moves from the dialyzer toward the patient. Once it reaches the patient, the blood tubing clamp 71 is used to clamp the blood tubing, ending the purification-return process. If one line's purification-return process is faster than the other, the faster line can be clamped first and the slower line can be clamped later.

[0313] Once the cleanse-return procedure is complete, the blood line is clamped and the patient is released from the dialysis machine. One embodiment of the system and method, implemented as shown in Figure 29A, utilizes the hydrophilic nature of the material used to form thin tubes within the dialyzer 14. When the material is wet, dialysate can pass through but air cannot. When implementing the embodiment shown in Figure 29A, air can enter the dialyzer 14 but cannot pass beyond the blood flow circuit 10.

[0314] In either implementation, the amount of dialysate that can pass through the dialyzer 14 is limited. This limit is imposed by the size of the compressed air tank 70, the amount of dialysate contained in the dialyzer 14, and, in the embodiment shown in FIG. 7B, the size of the fluid tank 75. It is advantageous to limit the amount of dialysate pumped into the dialyzer because providing the patient with excess fluid would negate the therapeutic benefits of removing fluid during treatment.

[0315] Another aspect of the present invention relates to a user interface for the system. The user interface is operated by an individual, such as a patient, family member, assistant, professional healthcare provider, or maintenance technician, to input selections, such as treatment options, and receive information, such as information regarding the treatment procedure, treatment status, device status / status, and / or patient condition. The user interface is attached to the treatment device and controlled by one or more processors of the treatment device. In other embodiments, the user interface may be a remote device that receives, transmits, or sends and receives data and instructions regarding the treatment procedure, treatment status, and / or patient condition. The remote device may be connected to the treatment device by any suitable technology, including wireless communication using optical and / or electronic radio, Bluetooth, RF frequencies, light frequencies, IR frequencies, ultrasonic frequencies, magnetic effects, etc., to transmit and / or receive data and instructions from or to the treatment device. In some embodiments, a display may be used to indicate when data and / or instructions are received by the treatment device or the remote device. The remote device may include an input device, such as a keyboard, touch screen, or capacitive input device, for inputting data and / or instructions to the treatment device.

[0316] In some embodiments, one or more processors of the processing unit may include a unique identification code, and the remote device may include functionality for reading and learning the processing unit's unique identification code. Alternatively, the user may program the processing unit with a unique identification code. The processing unit and the remote device may use the unique identification code to substantially avoid interference with other receivers, including other processing units.

[0317] In one set of embodiments, the treatment device may include one or more processors connected to a web-enabled server, which may also drive a user interface device. In one embodiment, the device uses an external CPU (e.g., a GUI graphical user interface) to communicate via Internet Protocol with a web-embedded server built into or connected to the treatment device. The web pages may be contained within the device, or the GUI may communicate directly via IEEE 802.11b or other similar wired or wireless Ethernet equivalents. The GUI may be operated by an individual, such as the patient, family member, assistant, professional healthcare provider, or maintenance technician, to input options, such as treatment options, and to receive information, such as information about the treatment procedure, treatment status, device status / status, and / or patient condition.

[0318] In other embodiments, an embedded web server built into or connected to the treatment device can communicate with appropriate sites on the Internet. The Internet site may require a password or other user credentials for access. In other embodiments, different types of users or access providers may have access to different information. For example, a patient or professional healthcare provider may have full access to a patient's treatment options and patient information, while a family member may be granted access to specific patient information, such as the condition and duration of a given treatment or treatment frequency. A maintenance technician, dialysis center, or treatment device provider may have access to other information, such as troubleshooting, preventative maintenance, and clinical trials. The use of a web-enabled server allows one or more individuals to simultaneously access patient information for various purposes.

[0319] The use of remote devices (e.g., via wired or wireless communication, Internet Protocol, or an internet site utilizing a web-enabled server) allows dialysis centers to more effectively monitor each patient and / or efficiently monitor multiple patients simultaneously. In some embodiments, the remote devices can function as night monitors or night alarms to monitor patients during overnight dialysis treatments and alert if a patient's condition does not meet certain parameters. In some embodiments, the remote devices can also be used to alert patients, family members, assistants, professional healthcare providers, or maintenance technicians. These alarms can alert individuals to specific conditions, such as, but not limited to, fluid leaks, blockages, temperatures outside normal parameters, etc. These alarms can be audible, visual, and / or vibrating alarms.

[0320] FIG. 60 illustrates an example of a user interface / treatment device combination. Specifically, FIG. 60 illustrates a perspective view of an exemplary hemodialysis system 6000 including a dialysis unit 6001 and a user interface unit 6002. In this example, the dialysis unit 6001 includes a housing 6004 containing components suitable for performing hemodialysis. For example, the dialysis unit 6001 may include the mixing circuit 25, the blood flow circuit 10, the balancing circuit 143, and the external dialysate circuit or outer dialysate circuit 142, as described, for example, in connection with FIG. 2A . The dialysis unit 6001 may also include all patient access and dialysate fluid connections necessary for operation of the system 6000.

[0321] The user interface unit 6002 includes a user interface 6003 that a user, such as a hemodialysis patient, may use to control the operation of the dialysis unit 6001 via a connection 6006. The connection 6006 may include a suitable data connection, such as a bus, a wireless connection, a connection via a local area network (e.g., an Ethernet local area network), and / or a connection via a wide area network (e.g., the Internet). The user interface unit 6002 further includes a housing 6005 containing components for enabling operation of the user interface. In the example of FIG. 60, the user interface 6003 includes a display screen with a touch-sensitive overlay that enables touch control and interaction with a graphical user interface displayed on the screen. However, many other types of user interfaces are possible, such as a screen with separate input mechanisms, such as a keyboard and / or a pointing device. The user interface 6003 may also include other features, such as push buttons, a speaker, a microphone for receiving voice commands, etc.

[0322] Although the hemodialysis system 6000 of Figure 60 includes a user interface unit 6002 that is physically coupled remotely from the dialysis unit 6001, many alternative configurations are possible. For example, the user interface unit 6002 may be mounted on or within the dialysis unit 6001. For convenience, a user interface unit 6002 so mounted may be removable from its mounting for use at another location or position.

[0323] FIG. 61 shows an exemplary hardware configuration for each of the dialysis unit 6001 and the user interface unit 6002. Each is controlled by a separate CPU, separating time- and safety-critical software from the user experience software. Once treatment has begun, it can be completed even if the user interface computer fails or is disconnected. This can be supported by having several physical control buttons and indicator lights implemented in the user interface unit 6002, duplicated to those connected to the control processor of the dialysis unit 6001. The dialysis unit 6001 includes an automation computer (AC) 6106 that controls the hardware actuators and sensors 6107 that communicate and monitor hemodialysis-related treatment. The automation computer 6106 includes an automation control unit 6108 that includes an automated computer processing unit 6109 and automated computer-readable media 6110. The automated computer processing unit 6109 includes one or more processors capable of executing instructions and operating on data stored on the automated computer-readable media 6110. The data may relate, for example, to a hemodialysis process that has been or can be performed on a patient. The system architecture provides the automation computer 6106 with software-accessible safety sensors 6107 and the ability to command fail-safe states (safely pausing or halting treatment). Parallel independent semiconductor device-based systems can perform similar software-controlled checks to provide redundant safety systems. This can be implemented, for example, in a field programmable gate array ("FPGA"), and can also command fail-safe states independently of the software system if one or more safety checks fail. The integrity of the pneumatic, hydraulic, and electrical systems can be checked both during and between treatment sessions. Instructions may comprise, for example, an operating system (e.g., Linux), application programs, program modules, and / or other coded instructions to perform specific processes.

[0324] The automated computer-readable medium 6110 may comprise any available medium that can be accessed by the automated computer processing unit (dialysis processing unit) 6109. For example, the automated computer-readable medium 6110 may comprise computer storage media and / or communication media. Computer storage media may include one or more of volatile and / or nonvolatile memory and removable and / or non-removable media implemented in any method or technology for storage of information such as computer-readable instructions, data structures, program modules, or other data. Examples of such computer storage media include, but are not limited to, RAM, ROM, solid-state disks, EEPROM, flash memory or other memory technology, CD-ROM, digital versatile disks (DVDs) or other optical disk storage, magnetic cassettes, magnetic tape, magnetic disk storage or other magnetic storage devices, or any other medium that can be used to store the desired information and that can be accessed by the automated computer processing unit 6109. Communication media typically embodies computer-readable instructions, data structures, program modules, or other data in a modulated data signal such as a carrier wave or other transport mechanism and includes any information delivery media. The term "modulated data signal" means a signal that has one or more of its characteristics set or changed in such a manner as to encode information in the signal. By way of example, communication media includes wired media such as a wired network or direct-wired connection, and / or wireless media such as acoustic, RF, infrared and other wireless media.

[0325] The various components of the automation computer 6106, such as the automation computer-readable medium 6110 and the automation computer processing unit 6109, may be electrically coupled via a system bus. The system bus may comprise any of several types of bus structures, including a memory bus or memory controller, a peripheral bus, and a local bus utilizing any of a variety of bus architectures. By way of example, such architectures include Industry Standard Architecture (ISA), Micro Channel Architecture (MCA), Enhanced ISA (EISA), Video Electronics Standards Association (VESA), and Peripheral Component Interconnect (PCI).

[0326] The automation computer 6106 may further include a dialysis universal serial bus (USB) interface 6113 to allow various input and / or output devices to be coupled to the automation control unit 6108. Examples of such input and / or output devices include monitors, speakers, printers, keyboards, pointing devices (e.g., mice), scanners, personal digital assistants, microphones, and other peripheral devices. USB is only one example of a type of interface that can be used to connect peripheral devices. Other interfaces may be used instead.

[0327] As described above, the dialysis unit 6001 includes components for performing and monitoring the hemodialysis process. Such components include sensors and actuators 6107. To couple the automation control unit 6108 to the sensors and actuators 6107, the automation computer may include a hardware interface 6111. The hardware interface 6111 may send inputs to and receive outputs from the sensors and actuators 6107.

[0328] The automation computer 6106 may further comprise an automation network interface 6112 that allows the computer to connect to network-connected devices, such as those in a local area network (LAN) and / or a wide area network (WAN). For example, the automation network interface 6112 may comprise a LAN, such as an Ethernet LAN, and / or a WAN, such as the Internet, and may allow the dialysis unit 6001 to exchange data with the user interface unit 6002 over a network 6114, which may be wired or wireless. Of course, the dialysis unit 6001 may alternatively or additionally exchange data with the user interface unit 6002 by way of a bus or other data connection.

[0329] The user interface unit 6002 includes a user interface computer 6119 that controls a user interface that displays information to and receives input from a user, such as a graphical user interface 6115. Like the automation computer 6106, the user interface computer 6119 includes a UI control unit 6116 having a UI processing unit 6117 and a UI computer-readable medium 6118, a user USB interface 6121, and a UI network interface 6120, each the same as or similar to their counterparts in the automation computer 6106. Additionally, the user interface computer 6119 may include a graphics interface 6122 that couples the UI control unit 6116 to the graphical user interface 6115. In a preferred implementation, the software of the user interface computer 6119 is not tasked with interpreting data received from the automation computer 6106, but rather with displaying the data in an understandable manner to the user.

[0330] FIG. 62 schematically illustrates various exemplary software processes that may execute on the automation computer processing unit 6109 and UIC processing unit 6117 of the automation computer 6106 and user interface computer 6119, respectively. The illustrated processes may be launched and monitored by executive processes. For example, the automation computer processing unit 6109 and UIC processing unit 6117 may each include an automation computer executive 6201 and a UIC executive 6207 to launch processes within a given processing unit and provide a communication mechanism to determine the execution status of child processes. The executives monitor each child process to ensure that each starts and continues to run as expected. Specifically, the automation computer executive 6201 and the UIC executive 6207 may detect hung processes. If a child process terminates or fails, each executive process may take appropriate action to ensure the system continues to operate safely. This may include terminating the process and notifying the UIC executive 6207, halting the system, or restarting non-safety-critical processes. In the UIC processor, this involves notifying an operator and completing the action using a hard key. The automation computer executive 6201 and UIC executive 6207 may use Linux parent-child process relationships to receive notifications from the operating system about child process terminations. This allows for handling abnormal process terminations and expected terminations during power-off sequences. The automation computer 6106, automation computer executive 6201, and UIC executive 6207 may have a message interface between them to share information about their respective running processes. Periodic sharing of state information allows both the automation computer processing unit (processor unit) 6109 and the UIC processing unit 6117 to have a consistent view of the state of all system processes.The automation computer executive 6201 can control watchdog signals to the electronics and put the machine into a fail-safe state if any child process becomes unresponsive or requires a fail-safe state. Preferably, this control can occur directly through hardware registers without the need for an I / O server.

[0331] As shown in the example of Figure 62, the automated computer processing device 6109 includes an I / O server process 6205. The I / O server process 6205 directly accesses hardware, such as the sensors and actuators of the dialysis unit, and provides an interface that allows other processes to request reading operations. For example, the I / O server process 6205 may isolate the machine controller from the details of the hardware by providing an interface for the machine controller 6202 to read and write the sensors and actuators. In the described embodiment, only the machine controller 6202 may communicate with the I / O server process 6205. The interface may be synchronized with a message queue.

[0332] The machine controller 6202, described above, serves as an interface for controlling the operation of the machine and reporting the machine's operational status. Specifically, the machine controller 6202 implements controllers that read sensors and set actuators via the I / O server process 6205. These controllers are designed to allow programming of functions (e.g., delivery and heating) with various parameters (e.g., flow rate, phase, pressure, and temperature) to support a variety of hemodialysis therapies. Controller configuration may be established by state machines that implement higher-level machine functions, such as priming and disinfection. The state machines configure flow path and controller setpoints based on machine capabilities and higher-level commands received from the therapy application 6203, described below. The machine controller 6202 may also perform safety cross-checks on various sensors to maintain safe and effective therapy. Machine status and health information may be recorded in a database by the machine controller 6202.

[0333] The therapy application 6203 drives the patient's therapy by commanding the machine controller 6202 to perform individual operations related to the hemodialysis process. Specifically, the therapy application 6203 may execute a state machine that implements therapy and controls the system's modes. The state machine controls, for example, priming the system with dialysate, connecting the patient to the machine, dialyzing the patient, rinsing the patient's blood back into the body, cleaning the machine, disinfecting the machine, running tests on machine components, replacing old or worn components, and waiting for the patient to return for the next treatment. The therapy application 6203 issues commands to the machine controller 6202 to implement therapy operations and requests status information from the machine controller 6202. To obtain patient, therapy, and machine information, the therapy application 6203 may interface with databases for accessing information and storing treatment status information. The therapy application 6203 may interface with a user interface model 6206 process, described below, to forward user selections to the user interface and report back therapy status. The Therapy Applications 6203 implements state machines including treatment preparation, patient connection, dialysis, solution infusion, patient disconnection, recycle preparation, disinfection, cleaning, and disposable replacement. The Therapy Applications 6203 process may also include a main control module responsible for sequencing the activities of all other Therapy Applications that prepare and deliver routine treatments.

[0334] Similar to the therapy application 6203, the user interface (UI) model 6206 executes on the automated computer processing unit 6109. The UI model 6206 aggregates information describing the current state of the system and the patient and supports changing the state of the system via operator input. The UI model 6206 separates the content of the user interface display from non-content-related aspects (e.g., presentation) by allowing the content of the user interface to be changed without affecting the underlying software that controls the user interface display. In this way, changes to the UI model 6206 can be made without affecting the visual experience provided by the user interface. The UI model 6206 does not have a display directly associated with it, but rather commands the graphical user interface (GUI) 6115 (FIG. 61) of the user interface unit 6002 to display screens and return information. For example, when the user navigates to a new screen, the UI model 6206 sends information to the user interface unit 6002 that is used in generating the new screen. The UI model 6206 may also validate user data received from the user interface unit 6002 and, once validated, forward the user data or commands based thereon to the therapy application 6203 .

[0335] To create the interactive display for the graphical user interface 6115 (FIG. 61) of the user interface unit 6002, a UI view process 6208 runs on the UIC processing unit (UI processor) 6117 of the user interface computer. The UI view process 6208 does not need to keep track of screen flow or treatment status. Instead, the UI view process 6208 receives information from a UI model 6206 running on the automation computer processing unit 6109, specifying what and how to display and what input the user can receive about the current state of the procedure. As a result, the graphical user interface 6115 can be terminated and restarted without affecting the operation of the system. In addition, the graphical user interface 6115 does not need to be responsible for validating user input. All inputs and commands received by the UI view 6208 are sent to the UI model 6206 for validation there. In this way, all safety-critical aspects of the user interface can be handled by the UI model 6206. Certain processes, such as those that are not safety-related, do not require the involvement of the UI model 6206. For example, the UI model 6206 does not need to perform any function to access information stored in a database on the user interface computer.

[0336] Also running on the UIC processing unit (UI processor) 6117, the remote access application 6210 provides an interface for external devices. For example, the remote access application 6210 may provide an interface for treatment monitoring, remote services, online assistance, and other external services if permitted by the user. The remote access application 6210 may be responsible for initiating remote connections, verifying access, and supporting communications from remote sites to the UI model 6206.

[0337] The database access application 6209 stores and retrieves data from one or more databases located, for example, on the user interface computer 6119 (FIG. 61). The database access application 6209 enables the storage and retrieval of records and provides a common access point for information required by the system, such as prescription, schedule, and history information. The database access application 6209 may manage the database files so that they are backed up regularly.

[0338] 62, the functionality of the user interface software may be split between the automation computer processor 6109 and the UIC processor 6117. The UI model 6206 and UI controller 6204 may work together to separate control of the UI data and state information of the automation computer 6106 so that software and screen design changes to the UI view 6208 only affect the non-safety-critical software of the user interface computer 6119. In this way, the UI model 6206 can be tested and executed at a safety-critical level while the UI view 6208 runs as a non-safety-critical process.

[0339] Generally, treatment and machine status information displayed on the user interface computer 6119 originates exclusively from the UI model 6206. According to one embodiment, all data displayed on the user interface computer 6119 originates from the UI model 6206 and is either retrieved directly from the database layer or temporary edited data entered by the user. The only local state information displayed or stored in the UI view 6208 may be this temporary edited data and details that enable local rendering of the information. In this manner, the UI model 6206 may maintain and control the display of all identified data. If desired, non-safety-related data may be handled exclusively by the UI view 6208. For example, changes to the display language or other display changes that do not affect safety-related content may be made using the UI view 6208 without any effect on the UI model 6206.

[0340] It should be recognized that the association of software processes with the automated computer processing unit 6109 and UIC processing unit 6117 illustrated in FIG. 62 is merely one example of a software configuration for performing the functions described above. Processes may be distributed in a variety of alternative ways between the automated computer processing unit 6109 and UIC processing unit 6117, and / or other local or remote processors. Also, not all processes are required for a hemodialysis system. Certain processes may be omitted or modified while maintaining hemodialysis system functionality.

[0341] FIG. 63 is an example illustrating how information related to the user interface flows between the hardware and software components of the user interface computer 6119 and the automation computer 6106. Information may flow and be handled such that safety-critical information is processed only at or below the UI model layer. Safety-critical information relates to the operation of the hemodialysis system. For example, safety-critical information may comprise the state of a dialysis process, the state of a screen in a graphical user interface, and / or algorithms for performing or monitoring therapy. In some examples, safety-critical information may be displayed in a graphical user interface. In that case, safety-critical information may comprise content that is critical to the operation of the hemodialysis system. Non-safety-critical information displayed in the user interface may comprise aspects of the display that relate to visual presentation and are not critical to the operation of the hemodialysis system.

[0342] As illustrated in FIG. 63, the UI model 6206, UI controller 6204, and therapy applications 6203 described in connection with FIG. 62 execute on the automation computer 6106. The UI view 6208, along with auxiliary applications 6301, execute on the user interface computer 6119. The database 6302 or its interface (e.g., a database server) may also reside on the user interface computer 6119. The UI model 6206 aggregates information describing the current state of the system and the patient and commands the graphical user interface to display screens and return information. For user control of the system, it validates user data and commands before forwarding them to the therapy applications. The UI model 6206 maintains display independence for the content of the user interface. The graphical user interface preferably does not maintain machine state information, allowing the user interface to be changed or temporarily disconnected without affecting the underlying software. The graphical user interface is not responsible for validating user input, but may restrict various input ranges, leaving validation the responsibility of the UI model 6206.

[0343] Considering first the flow of information between the UI view 6208 and the UI model 6206, the UI view acts as a client of the UI model, as described below. The UI view 6208 requests the current screen state from the UI model 6206, and the UI model responds to the request. The response determines the state of the UI view 6208's primary screen. The UI model 6206 may publish data and state information in sufficient detail to allow the UI view 6208 to present different subsets of display information depending on the level of detail requested by the user. For example, the UI view 6208 could use the same information from the UI model 6206 to present the same treatment state as either an overview or a step-by-step guide. Presentation of information may be based, for example, on the mode selected by the user (e.g., "expert" or "novice"). The UI model 6206 may provide the UI view 6208 with the ability to record sub-state information, such as the current presentation mode, in the UI model. This allows the GUI to resume operation in its previous state if the user interface computer 6119 is reset.

[0344] The UI model 6206 accepts user-entered data and requests, such as a request to start treatment, from the UI view 6208. Data integrity of information submitted via the UI view 6208 can be enhanced or ensured in several ways, such as sending data submitted via the UI view 6208 through the UI model 6206 for validation. That is, data can be edited locally in the UI view 6208, while accepted data can be moved to the UI model 6206 where it can be validated before being stored in the database 6302 and / or sent to the treatment application 6203. Validation can include, for example, verifying that the entered data is within expected ranges. The entered information can also be read back from the database 6302 by the UI model 6206 before being sent to the UI view 6208 for display to the user. This process can be used to ensure that the data stored in the database 6302 is correct or as intended by the user. Data integrity can also be enhanced by requiring validation of the entered data by the user or another party.

[0345] As shown in FIG. 63 , direct authority to control the therapy applications 6203 in response to input received from the user interface, thereby affecting machine state, may be restricted to the UI model / UI controller 6303 executing on the automation computer 6106. Additionally, direct authority to modify information in the database 6302 may be restricted to the UI model / UI controller 6303. In this case, at least in most circumstances, the UI view 6208 and auxiliary applications 6301 have read access to the database for actions such as viewing logs, but do not have write access to the database 6302. In this way, operations that may have safety-critical implications may be isolated on the automation computer 6106. Of course, it may be desirable for the UI view 6208 and auxiliary applications 6301 to have limited write access to the database 6302, such as writing to certain portions of the database or writing non-safety related data to the database. Additionally, in some embodiments, it may be desirable for the UI view 6208 to directly control aspects of the therapy applications 6203.

[0346] The auxiliary applications 6301 mentioned above may comprise, for example, a log viewer or a document viewer. These auxiliary applications 6301 may run on the user interface computer 6119 and operate in their own process space. However, to allow the UI view 6208 to control these applications, the auxiliary applications 6301 may be made clients of the UI view 6208. This allows the UI view 6208 to communicate with the applications in a standard way and have the UI view monitor their processes.

[0347] The UI controller 6204 may include a table-based hierarchical state machine (HSM) that determines the state of the screens displayed in the UI view 6208 based on data polled from the therapy application 6203, local timeouts, and command requests or data received from the UI view 6208. As shown in Figure 63, the UI controller 6204 may access and write data to the database 6302 upon request. The state of the hierarchical state machine of the UI controller 6204 may determine the main state of the set of screens that the UI view 6208 displays.

[0348] FIG. 64 illustrates an exemplary hierarchical state machine that the UI controller 6204 can use to determine the state of the screens displayed by the UI view 6208. As shown, the hierarchical state machine 6400 determines the state of a “normal” (i.e., non-alarm) level of interaction 6401, including the current functional state 6402 of the user interface and the current menu state 6403. The hierarchical state machine 6400 illustrated in FIG. 64 is merely an example and can be implemented in much greater detail. For example, a state 6404 called “Prepare” may encompass several states related to preparing for a procedure, including a “Source Collection” state, a “Chemical Installation” state, and a patient information entry and confirmation screen. The confirmation screen provides the user with an opportunity to return to a previous data entry screen so that inaccurate information can be corrected before exiting the “Prepare” state. The hierarchical state machine 6400 also illustrates a triggered alarm state 6405. Alarm states are described in connection with FIG. 65.

[0349] The UI view 6208 may have the ability to occupy the screen display at any time to display an alarm. An alarm state is triggered in certain circumstances, such as a fluid leak, blockage, or out-of-range temperature, that should alert a user or other individual to an abnormal or other noteworthy condition. When an alarm state occurs, the UI controller 6204 changes state. As shown in FIG. 65, when the UI view 6208 polls the UI model 6206 for the current state, the UI view 6208 changes the display view from a normal state 6501 to an alarm state 6502, which displays alarm information 6503. During an alarm state, the UI view 6208 may ensure that other information does not obscure the display of the alarm. However, even during an alarm state, the display may be configured to allow the user to activate a “Help” button to access additional information. In this case, the help information 6504 may be allocated so that it covers only a portion of the view. Safety-critical logic for the alarm display, such as mute logic, may be controlled by the automation computer 6106. For example, if a user wishes to silence an alarm, an indication of the silence request can be relayed back to the UI model / UI controller 6303, which can temporarily silence the audible alarm. In each of the alarm and normal states, alternative views 6505 and 6506, respectively, are possible.

[0350] As explained above, when an alarm occurs, the normal UI view state is terminated so that alarm state information can be displayed. When the screen is switched, local screen selection and / or edit data may be lost. Because it may be desirable to preserve this information, the UI view 6208 may request that the UI model / UI controller 6303 remember information about the screen displayed immediately prior to the alarm state (i.e., the screen associated with the normal state). If the normal state did not change upon the conclusion of the alarm, the UI view 6208 can retrieve the remembered information and restore the screen display. As an added benefit, this feature can also be used to restore a previous view if the user interface computer 6119 is inadvertently reset.

[0351] The following patent applications are incorporated herein by reference in their entirety: U.S. Patent Application No. 60 / 903,582, filed February 27, 2007, entitled "Hemodialysis System and Methods"; U.S. Patent Application No. 60 / 904,024, filed February 27, 2007, entitled "Hemodialysis System and Methods"; U.S. Patent Application No. 11 / 787,213, filed April 13, 2007, entitled "Heat Exchange Systems, Devices and Methods"; U.S. Patent Application No. 11 / 787,212, filed April 13, 2007, entitled "Fluid Pumping Systems, Devices and Methods"; U.S. patent application Ser. No. 11 / 787,112, filed April 13, 2007, entitled "Thermal and Conductivity Sensing Systems, Devices and Methods"; U.S. patent application Ser. No. 11 / 871,680, filed October 12, 2007, entitled "Pumping Cassette"; U.S. patent application Ser. No. 11 / 871,712, filed October 12, 2007, entitled "Pumping Cassette"; U.S. patent application Ser. No. 11 / 871,787, filed October 12, 2007, entitled "Pumping Cassette"; U.S. patent application Ser. No. 11 / 871,793, filed October 12, 2007, entitled "Pumping Cassette" and U.S. patent application Ser. No. 11 / 871,803, filed Oct. 12, 2007, entitled "Cassette System Integrated Apparatus."Additionally, the following are incorporated herein by reference in their entireties: U.S. Pat. No. 4,808,161, issued February 28, 1989, entitled "Pressure-Measurement Flow Control System"; U.S. Pat. No. 4,826,482, issued May 2, 1989, entitled "Enhanced Pressure-Measurement Flow Control System"; U.S. Pat. No. 4,976,162, issued December 11, 1990, entitled "Enhanced Pressure-Measurement Flow Control System"; U.S. Pat. No. 5,088,515, issued February 18, 1992, entitled "Valve System with Removable Fluid Interface"; "Interface"; U.S. Patent No. 5,350,357, issued September 27, 1994, entitled "Peritoneal Dialysis Systems Using Counter-Gravity Fluid Distribution and Pump Cassettes"; "Employing a Liquid Distribution and Pumping Cassette that Emulates Gravity Flow." Also incorporated herein by reference in their entirety are U.S. patent applications filed on even date herewith, entitled "Sensor Apparatus Systems, Devices and Methods" (attorney number F63, U.S. patent application Ser. No. 12 / 038,474), and U.S. patent applications filed on even date herewith, entitled "Cassette System Integrated Apparatus" (attorney number F62).

[0352] In addition, the following documents are incorporated herein by reference in their entirety and were filed on the same day herewith: U.S. Patent Application No. 12 / 198,947, entitled "Occluder for a Medical Infusion System"; U.S. Patent Application No. 12 / 199,055, entitled "Enclosure for a Portable Hemodialysis System"; U.S. Patent Application No. 12 / 199,062, entitled "Dialyzer Cartridge Mounting Arrangement for a Hemodialysis System"; No. 12 / 199,068, entitled "Modular Assembly for a Portable Hemodialysis System"; U.S. Patent Application No. 12 / 199,077, entitled "Blood Circuit Assembly for a Hemodialysis System"; U.S. Patent Application No. 12 / 199,166, entitled "Air Trap for a Medical Infusion Device"; U.S. Patent Application No. 12 / 199,176, entitled "Blood Line Connector for a Medical Infusion Device"; U.S. Patent Application No. 12 / 199,196, entitled "Reagent Supply for a Hemodialysis System" and U.S. patent application Ser. No. 12 / 199,452, filed Aug. 27, 2008, entitled "Hemodialysis System and Methods."

[0353] While several embodiments of the invention have been described and illustrated herein, those skilled in the art will readily envision various other means and / or configurations for performing the functions and / or obtaining the results and / or one or more advantages described herein, and each such variation / modification is deemed to be within the scope of the present invention. More generally, those skilled in the art will recognize that all parameters, dimensions, materials, and configurations described herein are exemplary, and that the actual parameters, dimensions, materials, and / or configurations will depend on the particular application in which the teachings of the present invention are used. Those skilled in the art will recognize or be able to ascertain, using routine experimentation, equivalents to the specific embodiments of the invention described herein. Accordingly, the foregoing embodiments are presented by way of example only, and it should be understood that the invention may be practiced otherwise than as specifically described and claimed, within the scope of the appended claims and equivalents thereof. The present invention relates to each individual feature, system, article, material, kit, and / or method described herein. Additionally, any combination of two or more of such features, systems, articles, materials, kits, and / or methods, even if they are not consistent with each other, is encompassed within the scope of the present invention.

[0354] All definitions should be understood to control for dictionary definitions, definitions in documents incorporated by reference, and / or ordinary meanings of the defined terms as defined and used herein.

[0355] It should be noted that as used in this specification and the appended claims, the indefinite articles "a" and "an" mean "at least one" unless the content clearly dictates otherwise.

[0356] It should be noted that as used in this specification and the appended claims, the phrase "and / or" refers to conjugated elements, i.e., "either or both" of elements that are present conjunctively in some cases and separately in other cases. Multiple elements listed with "and / or" should be construed in the same manner, i.e., "one or more" of the conjugated elements. Other elements may optionally be present other than the elements identified by the "and / or" clause, whether related or unrelated to such elements. Thus, as a non-limiting example, reference to "A and / or B," when used in conjunction with open language such as "comprising," includes, in one embodiment, A only (optionally including elements other than B); in another embodiment, B only (optionally including elements other than A); in another embodiment, both A and B (optionally including other elements); etc.

[0357] As used in this specification and the appended claims, "or" should be understood to have the same meaning as "and / or," as defined above. For example, when separating listed elements, "or" or "and / or" should be understood to be inclusive, i.e., including not only at least one of the elements or listed elements, but one or more, and optionally, elements not included in the list. Words clearly indicating otherwise, such as "only one of," "exactly one of," or, as used in the claims, "consisting of," indicate the inclusion of only one element of the elements or listed elements. Generally, as used herein, "or" when preceded by exclusive terms such as "either," "one of," "only one of," or "exactly one of" should be construed to indicate exclusive alternatives, i.e., "one or the other but not both." When used in the claims, "consisting essentially of" has its ordinary meaning as used in the field of patent law.

[0358] As used herein and in the appended claims, in reference to a list of one or more elements, the phrase "at least one" should be understood to mean at least one element selected from any one or more of the listed elements, but not necessarily including at least one of the specifically listed elements and not excluding any combination of the listed elements. This definition also allows for the optional presence of elements other than those specifically identified among the listed elements indicated by the phrase "at least one," whether or not related to the specifically identified elements. Thus, as a non-limiting example, "at least one of A and B" (or, equivalently, "at least one of A or B" or, equivalently, "at least one of A and / or B") means that in one embodiment, at least one refers to one or more As and no Bs (and optionally including elements other than B); in another embodiment, at least one refers to optionally one or more Bs and no As (and optionally including elements other than A); in yet another embodiment, at least one refers to one or more As and at least one, optionally one or more Bs (and optionally including other elements); etc.

[0359] Unless expressly indicated otherwise, it should be understood that in any claimed method comprising one or more steps or actions, the order of the steps or actions in the method is not necessarily limited to the order presented.

[0360] In the claims, transitional phrases such as "comprising," "including," "carrying," "having," "containing," "involving," "holding," "composed of," and the like, should be understood to mean open-ended, i.e., including but not limited to. Only "(essentially of)" are closed and semi-closed transitional phrases, respectively, as defined in the United States Patent Office Manual of Patent Examining Procedure, Section 2111.03.

Claims

1. A computer-readable storage medium having recorded thereon a program for causing a computer to execute the following steps, wherein the steps include: receiving inputs related to the dialysis process from a user interface associated with a user interface computer, the user interface being adapted to display information and receive inputs for controlling operation of the dialysis unit; 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; accessing the safety-critical information on behalf of the user interface computer; transmitting the safety-critical information to the user interface computer; a step of accessing screen design information stored in the user interface computer; a step of displaying information about the dialysis process on the user interface by using the safety-critical information and the screen design information; 1. A computer-readable storage medium comprising:

2. The safety-critical information is related to a display state of the user interface, the display state is based at least in part on a state of the dialysis process. The computer-readable storage medium of claim 1 .

3. The safety-critical information comprises data collected from the dialysis process. The computer-readable storage medium of claim 1 .

4. The user interface computer: configured to receive an input specifying a display mode; and and selecting a subset of the safety-critical information to use for displaying information related to the dialysis process based on the specified display mode. The computer-readable storage medium of claim 1 .

5. The procedure to be executed by the computer further comprises: receiving input related to the requested dialysis process; transmitting said input to said automated computer; and In response to receiving the input, issuing a command to the user interface to initiate the dialysis process; It is equipped with the automation computer having an interface to the dialysis unit; The computer-readable storage medium of claim 1 .

6. The procedure to be executed by the computer further comprises: verifying that the inputs related to the dialysis process are within expected ranges before issuing the commands. The computer-readable storage medium of claim 5.

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