Abstract:
A renal therapy machine includes a blood filter including a plurality of porous fibers; a blood circuit in communication with the blood filter; and a dialysate circuit in communication with the blood filter and operable with at least one pump, wherein the renal therapy machine is configured to perform a priming sequence in which a physiologically compatible solution, other than dialysate, primes the blood circuit and is flowed within the fibers and through pores in the fibers of the blood filter, and the pump of the dialysate circuit vents air from the blood filter into the dialysate circuit.

Description:
PRIORITY 
       [0001]    This application claims priority to and the benefit as a continuation application of U.S. patent application Ser. No. 14/594,349, entitled “Dialysis System Including Heparin Injection”, filed Jan. 12, 2015, which claims priority to and the benefit as a continuation application of U.S. patent application Ser. No. 13/346,357, entitled “Personal Hemodialysis System Including Priming Sequence and Methods of Same”, filed Jan. 9, 2012, now U.S. Pat. No. 8,932,469, which claims priority to and the benefit as a divisional application of U.S. patent application Ser. No. 12/257,014, entitled “Personal Hemodialysis System”, filed Oct. 23, 2008, now U.S. Pat. No. 8,114,276, which claims priority to and the benefit of U.S. Provisional Patent Application No. 60/982,323, entitled, “Personal Hemodialysis System”, filed Oct. 24, 2007, the entire contents of each of which are hereby incorporated by reference and relied upon. 
     
    
     BACKGROUND 
       [0002]    The present disclosure relates generally to medical treatments. More specifically, the present disclosure relates to medical fluid treatments, such as the treatment of renal failure and fluid removal for congestive heart failure. 
         [0003]    Hemodialysis (“HD”) in general uses diffusion to remove waste products from a patient&#39;s blood. A diffusive gradient that occurs across the semi-permeable dialyzer between the blood and an electrolyte solution called dialysate causes diffusion. Hemofiltration (“HF”) is an alternative renal replacement therapy that relies on a convective transport of toxins from the patient&#39;s blood. This therapy is accomplished by adding substitution or replacement fluid to the extracorporeal circuit during treatment (typically ten to ninety liters of such fluid). That substitution fluid and the fluid accumulated by the patient in between treatments is ultrafiltered over the course of the HF treatment, providing a convective transport mechanism that is particularly beneficial in removing middle and large molecules (in hemodialysis there is a small amount of waste removed along with the fluid gained between dialysis sessions, however, the solute drag from the removal of that ultrafiltrate is not enough to provide convective clearance). 
         [0004]    Hemodiafiltration (“HDF”) is a treatment modality that combines convective and diffusive clearances. HDF uses dialysate to flow through a dialyzer, similar to standard hemodialysis, providing diffusive clearance. In addition, substitution solution is provided directly to the extracorporeal circuit, providing convective clearance. 
         [0005]    Home hemodialysis (“HHD”) is performed in the patient&#39;s home. One drawback of home hemodialysis has been the need for a dedicated water treatment, which includes equipment, water connection and drainage. Installing and using those components is a difficult and cumbersome task that can require a patient&#39;s home to be modified. Nevertheless, there are benefits to daily hemodialysis treatments versus bi- or tri-weekly visits to a treatment center. In particular, a patient receiving more frequent treatments removes more toxins and waste products than a patient receiving less frequent but perhaps longer treatments. Accordingly, there is a need for an improved HHD system. 
       SUMMARY 
       [0006]    The present disclosure provides a home hemodialysis (“HHD”) system. In one embodiment, the home system includes a mobile cart and integral bag manager. A latch is pulled out to unlock door of the system instrument. The door can be opened to expose a latch hook and peristaltic pump heads. 
         [0007]    The instrument accepts a disposable unit which in one embodiment is loaded from above and slid to the right. The disposable unit pivots towards the machine interface, which allows peristaltic tube loops of the disposable unit to fit over peristaltic pump heads of the instrument. Also, supply lines of the disposable unit are passed over individual pinch valve plungers. 
         [0008]    The pinch valve plungers pinch the supply tubes against a pinch valve strike plate. The valve assembly is in one embodiment a motor-driven cam operated pinch valve subassembly. The motor in one embodiment is a stepper motor. 
         [0009]    The system in one embodiment includes a bellows or bladder that compresses a cassette against the instrument door using a pressure plate and gasket. These apparatuses are structured to accommodate an inline inductive heater provided with the disposable cassette. The bellows is air actuated in one embodiment. The instrument includes a primary coil that inductively heats conductive heating disks located within the cassette, which in turn heat fluid flowing through the cassette. 
         [0010]    A multi-peristaltic pump race retracts and extends in one embodiment illustrates to facilitate loading of the peristaltic tubes of the cassette onto the peristaltic pump heads. The race is then moved towards the tubes for operation. 
         [0011]    The system in one embodiment includes a manual blood pump operator, which allows the patient or caregiver to move the blood pump head manually. 
         [0012]    The system includes a bag management system having shelves that fold up, out of the way, and down, sequentially for placement of supply bags. The system in one embodiment supports up to five, six liter solution bags. The bags can be dual chamber bags. The shelves in an embodiment are provided with sensors that allow detection of whether the bags have been (i) loaded or not and (ii) opened or not for therapy. The sensors in one embodiment are capacitive sensors placed on opposite ends of the shelves. 
         [0013]    The disposable cassette in one embodiment connects fluidly to a heparin syringe for the injection of heparin into the blood circuit. The syringe fits into a luer connector assembly, which in turn is loaded into a syringe pump. The assembly is turned in the syringe pump to lock the syringe in the syringe pump for treatment. The assembly accommodates large syringes, such as fifty to sixty milliliter syringes, which can lock directly into the syringe pump. In one embodiment, the heparin line passes through the side of the cassette. Here, heparin can enter at the blood pump outlet just prior to the dialyzer inlet. 
         [0014]    The system also includes a retractable saline bag support rod. The saline in one embodiment connects to the cassette near the heparin line. A saline valve is located on each side of the blood pump to control the flow of saline to same. 
         [0015]    A dialyzer inlet pressure sensor interface in one embodiment doubles as a flow control valve. The cassette can also form an integral venus air separation chamber. 
         [0016]    Priming is performed in one embodiment via gravity. Gravity primes the venous line, the arterial line and the air trap (drip chamber). 
         [0017]    In another embodiment, priming is preformed via a combination of pumping dialysate and a physiologically safe fluid, such as saline. In particular, a hemodialysis machine can include a blood circuit, a dialysate circuit, a dialyzer placed in communication with the blood circuit and the dialysate circuit; and a priming sequence in which dialysate is used to prime a first portion of the dialysate circuit and a physiologically compatible solution, other than dialysate, is used to prime a second portion of the dialysate circuit, the dialyzer and the blood circuit. The first portion of the dialysate circuit includes a recirculation loop primed by a dialysate supply pump in one embodiment. The second portion of the dialysate circuit can then be located at least substantially between the recirculation loop and the dialyzer, and which is primed by at least one of a blood pump and a downstream dialysate pump. In one embodiment, a volumetric balancing unit separates the first and second portions of the dialysate circuit. 
         [0018]    The cassette in one embodiment uses balance tubes to balance fresh and spend dialysate flow. The balance tubes have outlets at the top of the tubes when mounted for operation to allow air to leave the tubes. The cassette also employs diaphragm valves that operate with a compliance chamber that seals against backpressure. 
         [0019]    For instance, a hemodialysis machine can include a dialysis instrument having at least one peristaltic pump actuator and first and second pneumatic valve actuators. The instrument operates with a disposable cassette, the disposable cassette including a rigid portion, with at least one peristaltic pump tube extending from the rigid portion for operation with the at least one pump actuator. The rigid portion defines first and second valve chambers in operable connection with the first and second valve actuators, respectively, the first and second valve chambers communicating fluidly with each other, at least the first valve chamber communicating fluidly with a compliance chamber, the compliance chamber absorbing energy from a pneumatic closing pressure applied to close the first valve chamber, so as to tend to prevent the pneumatic closing pressure from opening an existing closure of the second valve chamber. 
         [0020]    The machine in one embodiment includes a vacuum applied to the compliance chamber to absorb the energy from the pneumatic closing pressure applied to close the first valve chamber. 
         [0021]    In the above example, a flexible membrane can be sealed to the rigid portion, the pneumatic closing pressure applied to the membrane to close the first valve chamber. Here, the compliance chamber is formed in part via a portion of the flexible membrane, wherein the flexible membrane portion is configured to absorb the energy from the pneumatic closing pressure. The cassette can alternatively include a flexible diaphragm located on an opposing side of the rigid portion from the flexible membrane, the compliance chamber formed in part via the flexible diaphragm, the flexible diaphragm configured to absorb the energy from the pneumatic closing pressure. 
         [0022]    The disposable cassette can have multiple compliance chambers operating with different sets of valve chambers. The compliance chamber aids both upstream and downstream valves. The compliance chamber overcomes a backpressure applied by the closing of the second valve chamber to the first valve chamber, to allow the first valve chamber to close properly. 
         [0023]    In another compliance chamber embodiment, the dialysis instrument has a pump actuator and first and second valve actuators. A disposable cassette is operable with the dialysis instrument, the disposable cassette including a pump portion operable with the pump actuator, the first and second valve chambers communicating fluidly with each other, at least the first valve chamber communicating fluidly with a compliance chamber, the compliance chamber negating a first backpressure due to a pneumatic closing pressure used to close the first valve chamber to help to ensure the pneumatic pressure applied to the first valve chamber will close the first valve chamber against a second backpressure from an existing closure of the second valve chamber. Here, a pneumatic pressure applied to the second valve chamber can be the same as the pneumatic pressure applied to the first valve chamber. The first backpressure would exist around an outside of a port of the first valve chamber if not for the compliance chamber, the second backpressure existing inside the port. As before, the compliance chamber is further configured to tend to prevent the pneumatic pressure applied to the first valve chamber from opening the closed second valve chamber. And, the machine in one embodiment includes a vacuum applied to the compliance chamber to ensure the pneumatic pressure applied to the first valve chamber will close the first valve chamber. 
         [0024]    In a further compliance chamber embodiment, the dialysis instrument has a pump actuator and first and second valve actuators. The disposable cassette is operable with the dialysis instrument, the disposable cassette including a pump portion operable with the pump actuator, and first and second valve chambers operable with the first and second valve actuators, respectively, the cassette further includes a compliance chamber in fluid communication with the first and second valve chambers, the compliance chamber defined at least in part by a rigid wall of the cassette and a diaphragm located on an opposing side of the rigid wall from the first and second valve chambers. The rigid wall in one embodiment defines first and second apertures that allow the first and second valve chambers to communicate fluidly, respectively, with the compliance chamber. The cassette can include a flexible membrane located on an opposing side of the cassette from the diaphragm, the membrane for closing the first and second valve chambers. Again, the compliance chamber can aid at least one of: (i) maintenance of an existing closure of the second valve chamber when the first valve chamber is closed; and (ii) a proper closure of the first valve chamber at a time when the second valve chamber is already closed. In one embodiment, the aiding is provided via a vacuum applied to the compliance chamber. 
         [0025]    In still a further compliance chamber embodiment, a dialysis instrument has a pump actuator and first and second valve actuator. A disposable cassette is operable with the dialysis instrument, the disposable cassette including a pump portion operable with the pump actuator, and first and second valve chambers operable with the first and second valve actuators, respectively. A compliance chamber is placed in fluid communication with the first and second valve chambers, the compliance chamber defined by in part by a flexible membrane used to close at least one of the first and second valve chambers, the valve chambers each defining an aperture for fluid communication with the compliance chamber. The disposable cassette can include a rigid wall, the first and second valves chambers extending from the rigid wall towards the flexible membrane, wherein the apertures of the first and second valve chambers are formed in the rigid wall, and wherein the rigid wall also forms a third, larger aperture to allow fluid flowing through the valve chamber apertures to communicate fluidly with the flexible membrane of the compliance chamber. Again, the compliance chamber aiding at least one of: (i) maintenance of an existing closure of the second valve chamber when the first valve chamber is closed; and (ii) a proper closure of the first valve chamber at a time when the second valve chamber is already closed. Again, the aiding can be provided via a vacuum applied to the compliance chamber. 
         [0026]    It is therefore an advantage of the present disclosure to properly seal valves in fluid communication with one another. 
         [0027]    It is another advantage of the present disclosure to provide an efficient priming technique that combines the use of dialysate and another physiologically safe fluid, such as saline. 
         [0028]    Additional features and advantages are described herein, and will be apparent from, the following Detailed Description and the figures. 
     
    
     
       BRIEF DESCRIPTION OF THE FIGURES 
         [0029]      FIG. 1  is a perspective view of one embodiment of a personal home hemodialysis (“HHD”) system having a mobile cart and integral bag manager. 
           [0030]      FIG. 2  illustrates the system of the present disclosure, in which a latch is pulled out to unlock a door. 
           [0031]      FIG. 3  illustrates the system of the present disclosure, in which a door is opened exposing a latch hook and peristaltic pump heads. 
           [0032]      FIG. 4  illustrates one embodiment of the system of the present disclosure, in which the door is hidden to more clearly show the door latch. 
           [0033]      FIG. 5  illustrates one embodiment of the system of the present disclosure, in which a disposable unit is loaded from above and slid to the right. 
           [0034]      FIG. 6  illustrates one embodiment of the system of the present disclosure, in which the disposable unit is pivoted forward towards the interface. 
           [0035]      FIG. 7  illustrates one embodiment of the system of the present disclosure, in which the disposable unit pivots forward and the tube loops fit over the peristaltic pump heads. 
           [0036]      FIG. 8  illustrates one embodiment of the system of the present disclosure, in which the supply lines are placed in operable communication with individual pinch valve plungers. 
           [0037]      FIG. 9  illustrates one embodiment of the system of the present disclosure, in which the supply lines are hidden to show pinch valve plungers. 
           [0038]      FIG. 10  is rear view of one embodiment of the system of the present disclosure showing a pinch valve strike plate. 
           [0039]      FIG. 11  is a perspective view of one embodiment of a cam operated pinch valve subassembly operable with the system of the present disclosure. 
           [0040]      FIG. 12  is another perspective view of the pinch valve subassembly of  FIG. 11 . 
           [0041]      FIG. 13  is a perspective view of the pinch valve subassembly of  FIG. 11  with its housing and motor hidden. 
           [0042]      FIG. 14  illustrates a stepper motor operating with the pinch valve subassembly of  FIG. 11 . 
           [0043]      FIG. 15  illustrates blood lines operable with the system of  FIG. 1 . 
           [0044]      FIG. 16  illustrates blood line clamps closed on the blood lines of  FIG. 15 . 
           [0045]      FIG. 17  illustrates one embodiment of a blood line clamp subassembly operable with the system of the present disclosure. 
           [0046]      FIG. 18  illustrates one embodiment of a blood line clamp manual override. 
           [0047]      FIG. 19  illustrates a user access to a manual override of the blood line clamps. 
           [0048]      FIG. 20  is a perspective exploded view of one embodiment of a door showing a pressure plate, gasket and bellows operable with the system of the present disclosure. 
           [0049]      FIG. 21  illustrates the system with a door cover removed exposing tubes for bellows. 
           [0050]      FIG. 22  illustrates the system with the door hidden to better show an inline heating system. 
           [0051]      FIG. 23  illustrates the system with the door and cassette hidden to better show a heater coil and wave heater disks. 
           [0052]      FIG. 24  illustrates a front view of a retracted peristaltic pump race of the system of the present disclosure. 
           [0053]      FIG. 25  illustrates a rear view of a retracted peristaltic pump race. 
           [0054]      FIG. 26  illustrates a rear view of the peristaltic pump race extended. 
           [0055]      FIG. 27  illustrates that an instrument housing supports the front of the pump race actuator shafts. 
           [0056]      FIG. 28  illustrates one embodiment of a manual blood pump operation of the system of the present disclosure. 
           [0057]      FIG. 29  illustrates a manual blood pump operation with the instrument door closed and latched. 
           [0058]      FIG. 30  illustrates one embodiment of a bag management system operable with the HHD system having shelves folded up and ready for placement of a first supply bag. 
           [0059]      FIG. 31  illustrates a supply bag placed on a bottom shelf of the bag management system. 
           [0060]      FIG. 32  illustrates one embodiment in which the bag management system can hold up to five solution bags. 
           [0061]      FIG. 33  illustrates the bag management system with all solution bags connected and bag peel seals broken. 
           [0062]      FIG. 34  illustrates the bag management system with capacitive sensors placed on opposite ends of the shelves. 
           [0063]      FIG. 35  illustrates one embodiment of a connection of disposable set to a heparin syringe. 
           [0064]      FIG. 36  illustrates the syringe and luer connector assembly loaded into a syringe pump. 
           [0065]      FIG. 37  illustrates the connector of  FIG. 36  rotated 45° to lock the syringe into the syringe pump. 
           [0066]      FIG. 38  illustrates that a large, e.g., 50/60 ml, syringe can lock directly into the syringe pump. 
           [0067]      FIG. 39  illustrates one embodiment of a syringe pump mechanism operable with the HHD system of the present disclosure. 
           [0068]      FIG. 40  illustrates one embodiment of a viewing window for viewing heparin delivery. 
           [0069]      FIG. 41  illustrates the heparin line passing through the side of the cassette and attaching to the backside of the instrument. 
           [0070]      FIG. 42  illustrates that heparin enters at the blood pump outlet just before the dialyzer inlet. 
           [0071]      FIG. 43  illustrates one embodiment of a saline bag support rod operable with the HHD system of the present disclosure. 
           [0072]      FIG. 44  illustrates the saline line connected to the cassette near the heparin line. 
           [0073]      FIG. 45  illustrates a saline valve located on each side of the blood pump. 
           [0074]      FIG. 46  illustrates that the saline valve ports feed into each side of the blood pump. 
           [0075]      FIG. 47  illustrates that a dialyzer inlet pressure sensor interface can serve additionally as a flow control valve. 
           [0076]      FIG. 48  illustrates the venous and arterial lines are connected together to form a priming loop. 
           [0077]      FIG. 49  illustrates one embodiment of a venous air separation chamber operable with the system of the present disclosure. 
           [0078]      FIGS. 50 and 51  illustrate one embodiment of a venous air separation chamber valve operable with the system of the present disclosure. 
           [0079]      FIG. 52  is a fluid schematic illustrating one possible fluid flow regime for the HHD system of the present disclosure. 
           [0080]      FIGS. 53A and 53B  illustrate one embodiment of a disposable set operable with the system of the present disclosure. 
           [0081]      FIG. 54  is a fluid schematic illustrating one embodiment for gravity priming of the venous line, the arterial line and the air trap (drip chamber). 
           [0082]      FIG. 55  is a fluid schematic illustrating one embodiment for pressurized priming of the dialyzer and purging of air from blood side circuit. 
           [0083]      FIGS. 56 and 57  are fluid schematics illustrating one embodiment for priming the dialysate circuit. 
           [0084]      FIG. 58  is a section view of one embodiment for balance tubes having outlets at the tops of the tubes, the tubes operable with the HHD system of the present disclosure. 
           [0085]      FIG. 59  is a fluid schematic illustrating the HHD system of the present disclosure performing hemodialysis. 
           [0086]      FIG. 60  is a fluid schematic illustrating the HHD system of the present disclosure performing pre-dilution hemofiltration. 
           [0087]      FIG. 61  is a fluid schematic illustrating the HHD system of the present disclosure performing post-dilution hemofiltration. 
           [0088]      FIG. 62  is a fluid schematic illustrating the HHD system of the present disclosure performing post-dilution hemodiafiltration. 
           [0089]      FIG. 63  is a fluid schematic illustrating one embodiment for closing an arterial line clamp, opening a saline valve and infusing saline bolus during therapy. 
           [0090]      FIG. 64  is a fluid schematic illustrating one embodiment for recirculating fresh dialysate in heater circuit and balance tubes to remove ultrafiltration (“UF”). 
           [0091]      FIG. 65  is a fluid schematic illustrating one embodiment for closing a venous line clamp, opening a saline valve and rinsing back blood from the arterial line. 
           [0092]      FIG. 66  is a fluid schematic illustrating one embodiment for closing an arterial line clamp, opening a saline valve and rinsing back blood from the venous line. 
           [0093]      FIG. 67A  is a perspective view of one embodiment of a disposable interface subassembly operable with the HHD system of the present disclosure. 
           [0094]      FIG. 67B  is another view of the disposable interface subassembly of  FIG. 67A . 
           [0095]      FIG. 67C  is an exploded view of an internal module operable with the subassembly of  FIGS. 67A and 67B . 
           [0096]      FIG. 68  is a perspective view illustrating springs at the four corners of the subassembly of  FIGS. 67A and 67B  that retract the internal module of  FIG. 67C . 
           [0097]      FIG. 69  is a perspective view illustrating the backside of one embodiment of a cassette interface faceplate operable with the HHD system of the present disclosure. 
           [0098]      FIG. 70  is a perspective view illustrating the backside of one embodiment of a membrane gasket operable with the HHD system of the present disclosure. 
           [0099]      FIG. 71  is a perspective view of the internal instrument components from the backside of the hemodialysis system, showing that there is room for additional, e.g., electrical, components. 
           [0100]      FIG. 72  is a perspective view of one embodiment of the HHD system operating in conjunction with an online dialysate generation system. 
           [0101]      FIG. 73A  illustrates one embodiment of a diaphragm valve assembly having a compliance chamber seal against backpressure, which is operable with the HHD system of the present disclosure. 
           [0102]      FIG. 73B  illustrates one embodiment of a valve assembly having compliance chambers. 
           [0103]      FIG. 74  is a perspective view of a disposable cassette having the valve assembly of  FIGS. 73A and 73B . 
           [0104]      FIG. 75  illustrates one embodiment of a peristaltic pump head sized to operate with multiple supply lines for mixing different fluids of the HHD system of the present disclosure. 
       
    
    
     DETAILED DESCRIPTION 
       [0105]    Referring now to the drawings,  FIG. 1  illustrates one embodiment of a system  10  sitting idle with its dust cover (not illustrated) removed. A handle  12  for a cart  14  is located in a lowered position to minimize the space that system  10  consumes. Shelves  16  for the supply bags (shown below) are also shown in a lowered or “down” position, which minimizes the height of system  10 . 
         [0106]    System  10  is programmed in an introductory state to instruct the user to open a door  18  shown in  FIG. 2 .  FIG. 2  illustrates a close-up view of system  10  with a latch  34  pulled out to unlock door  18 . Once door  18  is unlocked as seen in  FIG. 3 , it swings open, e.g., about forty-five degrees, and is held in the open position by a stop (not seen), so that a disposable set (shown below) can be loaded or unloaded. 
         [0107]      FIG. 3  illustrates instrument  20  of system  10  with door  18  held in the open position, exposing multiple peristaltic pump heads  22 , a latch hook  24 , inductive heater coil  26  and a slotted area  28  for the blood lines (not illustrated) to run to and from the patient. Ultrasonic air bubble detectors and optical blood/saline/air detectors are integrated into the molded slotted area  28  just above a cutout in the slot for the venous and arterial line clamps. The cutout located in slotted area  28  accommodates the venous and the arterial line clamps.  FIG. 16  shows the venous and arterial line clamps  76  in the closed position, in which the clamps extend through a respective cutout. In an alternative embodiment, the inductive heater coil  26  is retracted into the system to facilitate loading. 
         [0108]    In  FIG. 4 , door  18  is not shown for clarity to illustrate latch  34  and latch hook  24 , wherein latch  34  mechanically engages latch hook  24  to hold door  18  closed against the main portion of instrument  20 . One suitable latch assembly is shown and described in FIGS. 11 and 13 of U.S. Pat. No. 6,261,065, “System and Methods for Control of Pumps Employing Electrical Field Sensing”, the pertinent portions of which are incorporated herein expressly by reference. 
         [0109]    As seen in  FIG. 5 , once door  18  has been opened, system  10  prompts the user to load the disposable set. A cassette  40  of the disposable set is lowered into the bag of instrument  20  and moved to the right (with respect to the orientation of instrument  20  in  FIG. 4 ). Cassette  40  is loaded starting at the upper left side of open door  18 , so that the patient&#39;s blood lines extending downwardly from cassette  40  do not interfere with the loading procedure. The patient&#39;s left hand can grasp a dialyzer  36  connected to cassette  40 , while the patient&#39;s right hand can grasp a tubing bundle  38  formed by the supply and drain lines. Single handed loading is also possible, e.g., using right hand only grasp bundle  38  to move both cassette  40  and dialyzer  36 . 
         [0110]    As seen in  FIGS. 6 and 7 , door  18  pivots cassette  40  forward towards a cassette interface  50  of instrument  20  when an opening  42  in cassette  40  is located directly over the inductive heater transformer coil  26 . In an alternative embodiment, transformer coil  26  is retracted to facilitate loading of cassette  40 . In such case, coil  26  is then extended into operating position after cassette  40  is loaded against interface  50 . A bezel (not shown) provides locating stops for stopping cassette  40  in the vertical and horizontal directions. 
         [0111]    As cassette  40  mates with the cassette interface  50 , the peristaltic pump tubing loops  44  of cassette  40  slip over the vertically aligned pumping heads  22 . A pump race  46  is retracted automatically upwardly when door  18  is opened to provide clearance between the pump heads  22  and pump race  26  to facilitate the loading of pump tubing  44  and cassette  40 . 
         [0112]      FIG. 8  illustrates the supply lines  38   a  to  38   e  of bundle  38  (number of supply lines  38  can vary) passing over retracted pinch valves  48 . System  10  also retracts pinch valves  48  automatically when door  18  is opened to facilitate the loading of bundle  38  and cassette  40  against interface  50  of instrument  20 . System  10  opens and closes pinch valves  48  in a controlled manner, eliminating the need for manual clamps on supply lines  38   a  to  38   e .  FIG. 9  is shown with supply lines  38  removed to more clearly illustrate pinch valve plungers  48 . 
         [0113]      FIG. 10  further illustrates pinch valve  48 /supply line  38  interaction. Pinch valves  48  pinch supply lines  38  closed against a strike plate  52 . In  FIG. 10 , four pinch valves  48  for supply lines  38   b  to  38   e  are pinching a respective supply line closed against strike plate  52 , while a fifth pinch valve  48  is retracted, allowing supply line  38   a  to be open. 
         [0114]      FIGS. 11 and 12  illustrate a pinch valve subassembly  60 , in which three of the five plungers  48  are extended (closed state). Clamp heads  54  are connected to a pinch valve body  62  of subassembly  60 .  FIG. 13  is shown with body  62  removed to illustrate springs  56  that spring load pinch valve plungers  48 , e.g., so as to be normally closed. Springs  56  preload pinch valve plungers  48 , allowing for variations in the wall thickness of supply tubes  38 .  FIG. 13  also illustrates that clamp heads  54  are formed with cam followers  58 , which ride on associated cam lobes  62  coupled to a camshaft  64  ( FIGS. 11 and 14 ). A motor  66 , e.g., a stepper motor, is coupled to a drive camshaft  64 .  FIG. 14  illustrates that in one embodiment, the individual cam lobes  62  each define apertures configured fit onto a keyed portion  68  of shaft  64 .  FIG. 14  further illustrates the interaction of cam followers  58  and cam lobes  62 . 
         [0115]      FIG. 15  illustrates that when cassette  40  is loaded into instrument  20  of system  10 , blood lines  72  and  74  exit to the lower left of door assembly  90  with venous and arterial line clamps  76  ( FIG. 16 ) open initially.  FIG. 16  illustrates that venous and arterial line clamps  76  pinch bloodlines  72  and  74  against housing portion  78  of instrument  20  to close bloodlines  72  and  74 . During normal operation, system  10  operates clamps  76  independently as needed.  FIG. 17  is shown with housing portion  78  and door assembly  90  removed to more fully illustrate venous and arterial line clamp subassembly  70 . A strike part of housing portion  78  seen in  FIG. 16  is located between the venous and arterial lines  72  and  74  and pinches the lines together with the clamping levers  76  when closed. 
         [0116]      FIG. 18  illustrates the venous and arterial line clamp subassembly  70  less a housing  77  shown in  FIG. 17 , in which clamps  76  are in the open position. Subassembly  70  includes bellows  80  that hold clamps  76  open during normal operation. Subassembly  70  also allows for an Allen wrench  82  with a T-handle  84  to be used to operate a worm gear  86  that is coupled operably to a cam  88 , which cooperate to manually open both the venous and arterial line clamps  76  if need be. In an alternative embodiment, subassembly  70  includes dual worm gears and a split cam, so that the venous and arterial line clamps  76  can be manually operated independently.  FIG. 19  illustrates the placement of the T-handle Allen wrench  82  with respect to instrument  20  when the venous and arterial line clamps  76  are operated manually. In one embodiment, system  10  causes an, e.g., red, flag (not illustrated) to protrude when the clamps  76  have been opened manually. The flag retracts when the manual override is not engaged. 
         [0117]      FIG. 20  illustrates an exploded view of the door assembly  90  taken from inside instrument  20 . A pair of bellows or bladders  92   a  and  92   b  pushes a plate  94  having a gasket  96  to press the cassette  40  (not seen here) against the disposable interface  50  (not seen here). A space between bladders  92   a  and  92   b  is provided to accommodate the inductive heater coil  26  extending from disposable interface  50 . Alternatively, instrument  20  provides a single bellows (bladder) to press cassette  40  against the disposable interface  50 , which has an internal opening to accommodate heater coil  26  extending from disposable interface  50 . 
         [0118]    In an alternate failsafe embodiment (not illustrated), the bellows  92   a  and  92   b  are replaced by a cavity with a diaphragm that is connected sealably to front pressure plate  18 . Springs are located between front pressure plate  18  and the back wall of the cavity and press cassette  40  against disposable interface  50 , except when a vacuum is present within the cavity. In the alternative embodiment, system  10  can also introduce positive pressure into the cavity to increase the sealing force. 
         [0119]      FIG. 21  illustrates system  10  with the door cover  98  ( FIG. 20 ) removed. Pneumatic lines  102   a  and  102   b  to bellows  92   a  and  92   b , respectively, are shown teed together before the exiting door  18  through a hollow hinge  104 . A vertical metal bar  106  completes a circuit for the inductive heater transformer primary coil  26  when the door  18  is closed against interface  50  of instrument  20 .  FIG. 22  is also shown with door  18  removed to illustrate the inductive heating system including transformer coil  26  and a wave-shaped disk or disks  108  located in disposable cassette  40 , which form a secondary coil that heats dialysis fluid due to i 2 R losses.  FIG. 23  removes cassette  40  to show inductive heater  100  more clearly. Heater  100  transfers energy from the inductive coil of the transformer  26  into wave washers  108   a  and  108   b  that are located within cassette  40 . Washers  108   a  and  108   b  in turn heat dialysate as it flows through cassette  40 . 
         [0120]      FIG. 24  illustrates the front of the instrument  20  with door assembly  90  and device housing hidden to expose a mechanism  110  that extends and retracts triple peristaltic pump race  46 . Mechanism  110  includes four idler gears  112  that tie geared triple cams  114  together to move race  46  to extend (towards tubing  44 ) and retract (from tubing  44 ) smoothly. Mechanism  110  is configured such that race  46  extends towards tubing  44  only after door  18  is closed and latched to preclude the operator from being exposed to any moving components. The centers of pump heads  22  are aligned to provide clearance between the pump heads and triple race  46  when the race is retracted. 
         [0121]      FIG. 25  illustrates the backside of the retractable triple peristaltic pump race  46  and mechanism  110  for moving race  46 . Cams  114  are located at each end of race mechanism  110  and race  46 . A middle cam  114  is also provided. Each idler gear  112  ( FIG. 12 ) includes a shaft  113  that transmits rotational motion from the idler gears to all three cams  114  simultaneously. Cams  114  each include lobes  116  that rotate simultaneously and in concert within large rounded end slots  118  to simultaneously and evenly extend and retract race  46 . Shafts  113  of idler gears  112  ( FIG. 24 ) maintain the horizontal orientation of the peristaltic pump race  46  as the race moves up and down. 
         [0122]      FIG. 25  illustrates the cam lobes  116  rotated simultaneously and in concert upwardly, pushing the pump race  46  away from gear motors  120  that are coupled to pump heads  22 . The open parts of the horizontally stabilizing idler guide slots are above the shafts  113  of idler gears.  FIG. 26  illustrates the cam lobes  116  rotated simultaneously and in concert downwardly, pushing pump race  46  towards the pump gear motors  120  coupled to pump heads  22 . The open parts of the horizontally stabilizing idler guide slots  122  are now below the shafts  113  of idler gears  112 . 
         [0123]      FIG. 27  illustrates molded support bosses  124  secured to instrument  20  that support shafts  113  of the idler gears  112  and support the shafts  115  of cams  114  on one end. A bar (not shown here but shown in  FIG. 71 ), which mounts to bosses  124 , supports the shafts  113  of gears  112  and shafts  115  of cams  114  on their other ends. A motor (not illustrated) that drives cams  114 , which operate the retractable pump race  46 , is attached to any of the shafts  115  of any of cams  114 . Attaching the motor to the shaft of center cam  114  may be preferred so that clearance in the gear train is symmetric with respect to outer cams  114 . 
         [0124]      FIGS. 28 and 29  illustrate that system  10  includes a crank  130  that is connected to the blood pump head  22  to operate the head manually. Manual return of the blood contained within the extracorporeal circuit is necessary in the event of a failure of system  10  or after an extended power failure. It is typically necessary to manually operate the venous and arterial line clamps  76  (from a failed closed state) before being able to return the blood in extracorporeal circuit to the patient.  FIG. 29  also illustrates that door  18  in one embodiment defines an opening or aperture  132  through which manual crank  130  for the blood pump  22  can be inserted with the door closed. Crank  130  includes a large gripping handle  134  and crankshaft  136 , which is sufficiently long to allow the user to easily turn blood pump head  22 . In an alternate embodiment, manual crank  130  is built into the door assembly  90  and is accessible to engage pump head  22  when door  18  is opened and hinged away from machine interface  50 . 
         [0125]    As seen in  FIG. 30 , in one bag management embodiment, system  10  prompts the user initially to fold up all of bag shelves  16  except for the bottom shelf  16 . The user is then able to break a peel seal of a dual chamber bag (if used), place the first solution bag  140  on bottom shelf  16  and connect the bag to the bottom supply line  38   e  extending from disposable cassette  40 , as shown in  FIG. 31 . When shelf sensors  138  detect that the bag has been placed onto first shelf  16  and that the peel seal  142  has been broken, system  10  prompts the user to place a second bag  140  on the second lowest shelf  16 , and so on. System  10  continues to prompt the user to place solutions bags  140  onto shelves  16  and connect the bags to supply lines  38  until all of shelves  16  are filled, as shown in  FIG. 32 . 
         [0126]    As shown in  FIG. 32 , a peel seal  142  of dual chamber bag  140  present on the top shelf  16  is not broken, a condition which sensors  138  can sense, causing system  10  to instruct the user to break peel seal  142  before continuing with treatment. One such sensor arrangement and peel seal open check is described in U.S. patent application Ser. No. 11/773,742, entitled “Mobile Dialysis System Having Supply Container Detection”, filed Jul. 5, 2007, assigned to the assignee of the present disclosure, the pertinent portions of which are incorporated herein expressly by reference.  FIG. 33  illustrates all solution bags  140  with peel seals  142  broken, such that treatment can continue. 
         [0127]      FIG. 34  illustrates one embodiment for the placement of the capacitive sensors  138  that detect the presence of the solution bags, whether peel seal is broken, and perhaps even whether the same solution is present in each bag  140 . Other sensors or combinations of sensors can be used alternatively, including optical sensors, inductive sensors, bar code readers, radio frequency identification (“RFID”) tags and cameras. 
         [0128]      FIG. 35  illustrates a luer connection assembly  144 , which is located on an end of a heparin line  146 , which in turn is connected to disposable cassette  40 . A heparin syringe  148  ranging in size from ten milliliters to sixty milliliters, can be connected to luer connection assembly  144  of the disposable set and is inserted with the plunger  150  pointing down into a syringe pump  152  as shown in as shown in  FIG. 36 . The luer connection assembly  144  is then rotated to lock the syringe in place as shown in  FIG. 37 . Syringe  148 , for sizes larger than 30 milliliters, is inserted with the plunger  150  pointing down into a syringe pump  152  as shown in as shown in  FIG. 38 . The integral grip  149  on the larger heparin syringes is rotated forty-five degrees to lock the syringe  148  into the syringe pump  152  as shown in  FIGS. 37 and 38  versus grip  149  shown in  FIG. 36 . 
         [0129]    Syringe pump  152  is shown in more detail in  FIG. 39 . Pump  152  includes a stepper motor  154 , gears  156 , guide rails  158  and a concave push plate  160  that self-centers on the end of the syringe plunger  150 . Air exits syringe  148  above the heparin and is purged during the priming of the extracorporeal circuit because syringe  148  is inverted for use. Stepper motor  154  increments 0.9 degrees per step in one implementation. Pump  152  and assembly  144  are sized to accept nearly any size of syringe  148 . The user inputs the syringe stroke length and syringe stroke volume into system  10 . System  10  can thereafter determine the volume of heparin to be delivered. 
         [0130]    Smaller syringes  148  are visible through a window  162  in the side of the pump as shown in  FIG. 40 . Larger syringes housings are visible since they are not inserted into syringe pump  152  and remain outside of instrument  20  as illustrated in  FIG. 38 . Should a saline or dialysate bag leak, or be spilled, onto instrument  20 , the liquid could flow into the heparin pump and out the opening in side window  162  but would not flow inside the instrument, where the fluid could damage instrument  20 . 
         [0131]      FIGS. 41 and 42  illustrate that heparin line  146  passes through an air bubble detector  164  to cassette  40 . System  10  introduces heparin into the patient&#39;s blood stream at the outlet  166  of the blood pump just before the blood passes into the dialyzer. The internal volume of the heparin line is essentially that of a very small diameter tube of minimum length. A diaphragm actuated pinch valve  165  (plunger only shown in  FIG. 41 ), which does not add to the internal volume of the heparin line, can be provided to block the flow of heparin to cassette  40 . 
         [0132]      FIG. 43  illustrates a support rod  168  that collapses into instrument  20  when not in use. Support rod  168  supports a saline bag  170  that is used for priming system  10  and rinsing blood back to the patient at the end of the therapy. Alternatively, rod  168  is detachable from instrument  20  when not in use. 
         [0133]      FIGS. 43 and 44  illustrate that saline line  172  enters instrument  20  adjacent to the entry of heparin line  164  (see also  FIG. 41 ).  FIG. 45  illustrates that two saline flow control valves  174   a  and  174   b  are located on each side of blood pump tubing loop  44 . The center port from each of the valves feeds directly into blood flow into, or coming from, the blood pump as shown in  FIG. 46 . The third saline valve  174   c  is located on the backside of cassette  40  as seen in  FIGS. 45 and 46  and is positioned to put saline directly into a venous air separation (drip) chamber  176 . The saline valve  174   a  on the blood pump outlet, and the saline valve  174   b  leading to dialyzer  36 , are opened sequentially to gravity prime the arterial blood line and the venous drip chamber  176  as illustrated later in  FIG. 54 . 
         [0134]    As seen in  FIG. 47 , a normally evacuated dialyzer inlet line pressure transducer interface  178  is pressurized so that it operates as a flow control valve, preventing saline from backflowing into the dialyzer or filter  36 . The gravity head from the saline bag causes saline to flow into the blood circuit and into the reversed rotating pump inlet  180  (the outlet under normal operating flow) when saline valve  174   a  is opened. The reversed flow blood pump head  22  draws saline from the saline bag and pumps it through reversed flow outlet  182  (the inlet under normal operating conditions) and down the arterial line  186 . 
         [0135]    As seen in  FIG. 48 , the venous line  184  and arterial line  186  are connected in series during priming so that air is purged from both lines via venous line drip chamber  176  shown in  FIG. 49 . Standard connections  188  ( FIG. 48 ) can be used to connect the venous line  184  and arterial line  186  in a closed loop. Gravity prevents air from being drawn from the saline bag as long as the bag contains saline. Saline flows slowly into the venous air separation chamber  176  in a “reverse” direction (from normal blood flow) during priming. 
         [0136]    In  FIG. 49 , the inverted-U shaped venous air separation chamber  176  has a vent port  190  located at its top, so that air can gather there and be vented to the drain.  FIG. 50  shows a valve  196  located on the opposite side of the cassette  40  from vent port  190 , which is opened whenever air needs to be vented from the chamber. A second vent valve  192  also shown in  FIG. 50  can be placed optionally in series with first vent valve  196  and operated sequentially so that predetermined volumetric increments of air can be vented from system  10  to a controlled vent volume  194  shown in  FIG. 51 . As seen in  FIG. 51 , port  190  connected to the center of the cassette-based diaphragm valve  196  communicates with air separation chamber  176  so that the “dead” volume needed for these apparatuses is minimized. Valve  196  seals well against the pressure present in the venous air separation chamber. Saline bags can be replaced during a therapy since they can be primed directly into the drip chamber  176  using the third saline valve  174   c  ( FIG. 49 ). 
         [0137]      FIG. 52  is a schematic of one embodiment of a fluid management system associated with the disposable set. In general, the fluid management system includes a blood circuit  210  and a dialysate circuit  220 . System  10  operates the disposable set to provide the hemodialysis therapy. Set  200  of  FIGS. 53A and 53B  illustrates an embodiment of a disposable set  200  operable with system  10 . Disposable set  200  includes cassette  40 , filter  36 , pump tubes  44 , supply tubes  38 , balance tubes  202 , arterial line  184  and venous line  186 , etc., discussed herein. 
         [0138]    Once disposable set  200  has been loaded into the hemodialysis system  10 , dialysate bags  140  have been connected, the saline bag  170  ( FIG. 43 ) has been connected and the heparin syringe  148  has been loaded, system  10  primes itself automatically starting with the blood side circuit. The heparin pump plunger  150  is moved forward until heparin is detected by heparin line air detector AD-HL shown in  FIG. 52 . Heparin valve V-H is then closed. Next, saline is flowed from the saline bag  170  into the blood side circuit  210  as illustrated in  FIG. 54 , first through valve V-SA and then through valve V-SDC. A level sensor L-ATB in the AIR TRAP drip chamber detects saline flow into the drip chamber  176  and determines when to close valves V-SA and V-SDC. 
         [0139]    As shown in  FIG. 55 , the post pump blood valve V-PPB is then closed, V-SV is opened and PUMP-Blood pumps saline in a reverse flow direction. Pressure sensor P-VL and level sensor L-ATB are used to determine when to open air vent valves V-AVB-P and V-AVB-S. The blood pump pushes the saline backwards down the arterial line and into the venous line. When saline reaches the venous air separator (drip chamber  176 ), the air will be separated from the fluid and will be discharged into a drain line  206  through vent valves V-AVB-P and V-AVB-S until the air separation chamber  176  is flooded with saline. 
         [0140]    Next, as seen in  FIG. 55 , saline is flowed up into the bottom of dialyzer  36  and up through its hollow fibers. Valve V-PPB is controllably opened so that the air that exits the top of the dialyzer  36  flows into the priming loop, becomes separated in air trap  176  and discharged to drain  206 . Saline is also flowed through pores of the fibers of dialyzer  36  to fill the housing of dialyzer  36 . System  10  monitors the pressure in the venous line using pressure sensor P-VL to maintain the blood side circuit  210  at a controlled pressure during priming. 
         [0141]    As seen in  FIG. 56 , spent dialysate pump, PUMP-DS and valves V-DS, V-B1-S1, V-B1-SO and V-DD vent air from the dialyzer housing to drain  206 . Valves V-DI-VEN, CK-VEN, V-DI-FIL, V-DI-PRE and CK-PRE are opened controllably to allow a predetermined volume of saline to be pushed into the dialysate circuit  220 , purging air from associated dialysate lines. A second saline bag  170  can be replaced during a therapy by selecting “replace saline bag”, causing the saline line to be primed automatically into the air trap  176 . 
         [0142]    As shown in  FIG. 56 , dialysate valve V-DB1 that is associated with the dialysate bag on the top shelf is opened so that dialysate can flow into the inlet of dialysate PUMP-DF. PUMP-DF pushes the dialysate through the inline fluid heater and into a dialysate side air trap  208 . Dialysate flows out the bottom of the air trap  208 , through valve V-FI and into balance tube B2, through valve V-B2-FI, pushing fluid out the other side of balance tube B2. The fluid exiting the other side of balance tube B2 flows through valve V-B2-SO and into the dialysate recirculating circuit  203  through valve V-DR. The recirculating circuit  223  tees into the supply line circuit  205  at the inlet to PUMP-DF. Pump-DS is operating at the same time drawing air, dialysate and/or saline from the blood side of the dialyzer, though the dialysate side of the dialyzer, into the remainder of the dialysate circuit. PUMP-DS pushes the fluid through valve V-B1-SI and into balance tube B1, pushing fluid out the other side of balance tube B1. The fluid exiting the other side of balance tube B1 flows through valve V-B1-FO and valve V-DI-FIL into the dialysate side of the dialyzer  36 . 
         [0143]      FIG. 57  is similar to  FIG. 56  except the roles of balance tubes  202  B1 and B2 are reversed. As fluid enters the dialysate circuit  220 , the pressure in the circuit increases, forcing air to be discharged under pressure to drain line  206  through open vent valves V-AVD-P and V-AVD-S. 
         [0144]      FIG. 58  illustrates balance tubes  202 . Instrument  20  includes pairs of optical sensors (not shown) operable with balance tubes  202  to determine an end of travel of a separator  212  located within each balance tube  202 . The optical sensors in one embodiment are reflective, so that an emitter and receiver of each sensor can be on the same (e.g., non-door) side of balance tube  202 . The sensors alternatively include emitters and receivers located on opposite sides of balance tubes  202 . Outlets  214  on both ends of both balance tubes  202  are at the balance tube tops when mounted for operation as shown if  FIG. 58 , so that air will pass through the balance tubes and not become trapped in the tubes as long as system  10  is level. Mechanical stops  216  limit the movement of separators  212  to that visible to the optical sensors. 
         [0145]      FIG. 59  illustrates HHD system  10  performing hemodialysis. Here, fresh dialysate is pushed from balance tubes  202  to dialyzer  36  via valve V-DI-FIL, while spent dialysate is removed from dialyzer  36  via valve V-DS to balance tubes  202 . 
         [0146]      FIG. 60  illustrates HHD system  10  performing pre-dilution hemofiltration. Here, fresh dialysate is pushed from balance tubes  202  to blood circuit  210  directly via valve V-DI-PRE, while spent dialysate is removed from dialyzer  36  via valve V-DS to balance tubes  202 . 
         [0147]      FIG. 61  illustrates HHD system  10  performing post-dilution hemofiltration. Here, fresh dialysate is pushed from balance tubes  202  to blood circuit  210  directly via valve V-DI-VEN, while spent dialysate is removed from dialyzer  36  via valve V-DS to balance tubes  202 . 
         [0148]      FIG. 62  illustrates HHD system  10  performing post-dilution hemodiafiltration. Here, fresh dialysate is pushed from balance tubes  202  to (i) dialyzer  36  via valve V-DI-FIL and (ii) blood circuit  210  directly via valve V-DI-VEN, while spent dialysate is removed from dialyzer  36  via valve V-DS to balance tubes  202 . 
         [0149]      FIG. 63  illustrates one embodiment for closing arterial line clamp V-ALC, opening a saline valve V-SA and infusing a saline bolus into blood circuit  210  during therapy. 
         [0150]      FIG. 64  illustrates one embodiment for recirculating fresh dialysate through Fluid Heater and recirculating circuit  223  and balance tubes B1 and B2 to remove UF. In  FIG. 64 , pump-DF pumps fluid in a loop that includes Fluid Heater since valve V-DBY is open. Valve V-FI is closed so no fresh dialysate is delivered to balance chambers  202 . Pump-DS pulls spent fluid from the dialyzer  36  through valve V-DS and pushes the spent fluid through valve V-B1-SI and into the right side of balance tube B1. Fresh fluid then flows from the left side of balance tube B1 through valves V-B1-FI and V-B2-FI and into the left side of balance tube B2. Spent fluid then flows out the right side of balance tube B2 through valves V-B2-SO and V-DD and into the drain line. In this manner, a volume of spent fluid is sent to drain  206  without a corresponding volume of fresh fluid delivered from supply bags  140  to either balance chamber B1 or B2. 
         [0151]      FIG. 65  illustrates one embodiment for closing venous line clamp V-VLC, opening a saline valve V-SA and rinsing back the arterial line  184 . 
         [0152]      FIG. 66  illustrates one embodiment for closing arterial line clamp V-ALC, opening a saline valve V-SA and rinsing back the venous line  186 . 
         [0153]      FIGS. 67A to 67C  illustrate a cassette interface assembly  250 , which houses, among other items, cassette interface  50 , door latch  24 , heater  26 , a bellows bladder  252  and an internal module  260 . Internal module  260  is bounded by interface plate  50  and a back plate  254 . Internal module  260  houses a plurality of gaskets  256 , a pneumatic valve assembly  258 , a pinch valve assembly  262 , and a plurality of manifold plates  264 . 
         [0154]    All or most all of the valves, pressure sensors, level sensors, etc., can be removed without disassembly of subassembly  250 . The inductive heater mechanism  26  and bellows bladder  252  (different from bladder  92  above) require removal of internal module  260 . To this end, four screws  266 , each with a spring  268 , fix a housing  270  of subassembly  250  to internal module  260 . Internal module  260  can be unbolted from screws  266 , so that springs  268  push internal module  260  forward and out of the housing  270 . Power and control connections (not shown) to subassembly  250  are also disconnected to remove internal module  260  completely. 
         [0155]    As seen additionally in  FIGS. 68 to 70 , four springs  268  on the backside of subassembly  250  retract the internal interface module  260  when bellows bladder  252  is not pressurized by pushing screens away from housing  270  and pulling interface module  260  along with the screws. When the bellows bladder  252  is pressurized, internal module  260  is pushed forward and applies pressure to cassette  40 , pushing the cassette against a door gasket, which seals fluid pathways on both the front side and the rear side of the cassette  40 . The membrane gaskets  256  on the internal module  260  mate up against the faceplate  50  of the interface module  250 . The faceplate  50  is configured so that it can support a vacuum between the cassette sheeting and pressure sensors, liquid level sensors, etc., bringing the sensors into intimate contact with the cassette sheeting and the fluid on the other side of the sheeting. System  10  is also configured to port a vacuum between the cassette sheeting and the thin sections of the membrane gasket  256  above the valves. This vacuum can be used to detect holes, tears or slits in the cassette sheeting before, and during a therapy. 
         [0156]      FIG. 71  is a view of the backside of system  10  with the cover removed. The open space houses interface assembly  250 , hinged shelves  16 , peristaltic pump motors  120  a pneumatic pump, a power supply, battery and electronics that operate the system. 
         [0157]      FIG. 72  illustrates system  10  operating alternatively with an online dialysate generation system  300 . System  300  generates dialysate online or on-demand, eliminating bags  140 , shelves  16  and multiple supply tubes  38 . A single supply tube  38  feeds from generation system  300  to instrument  20 . Water inlet line  302  and drain lines  304  lead to and from generation system  300 , respectively. 
         [0158]      FIGS. 73A, 73B and 74  illustrate a cassette  40  diaphragm valve chamber configuration  280 , which solves an inherent problem with diaphragm valves have when attempting to seal against downstream pressure because the pressure that is trying to seal off the valve is acting on an area that is just slightly larger than an area upon which the downstream pressure is acting. The difference between the two areas is the area defined by the top of the “volcano”. Also, if the downstream fluid volume is completely fixed when the diaphragm valve closes, further movement of the diaphragm is prevented after the initiation of the seal because of the incompressibility of the trapped fluid. The result is that the downstream pressure equals the valve sealing pressure. Diaphragm valve configuration  280  provides a diaphragm valve that can seal against both upstream and downstream pressure via a connection of two diaphragm valve chambers  282  and  284  placed in series. Diaphragm valve chambers  282  and  284  are connected fluidly via a compliance chamber  286 , which allows sheeting seals  288  of the cassette sheeting to close around respective volcano ports  290  of both valve chambers  282  and  284 . 
         [0159]    Chamber configuration  280  in both  FIGS. 73A and 73B  includes a rigid middle or base wall  281  from which valve ports  290  and the valve chamber walls extend upwardly. Wall  281  defines an aperture  283  for each valve chamber  282  and  284 . Fluid communicates between valve chambers  282  and  284  and compliance chamber  286  via apertures  283 . 
         [0160]      FIG. 73A  shows a cross-section of two diaphragm valve chambers  282  and  284  with an integral compliance chamber  286 , wherein the diaphragms can readily close seals  288  to ports  290 . Here, a vacuum is applied to a lower diaphragm  289  at the compliance chamber  286 . Diaphragm  289  is flexible and has a relatively large cross-sectional area to absorb the kinetic energy created by a pneumatic valve actuator applying a positive pressure Pa, such that the positive sealing pressure applied to one valve chamber  282  or  284  is much less likely to harm an existing seal of a fluidly connected upstream or downstream valve chambers. The negative pressure pulls sheeting  288  down around ports  290  and allows valve chamber  282  or  284  to be sealed against the backpressure applied by its own sealing pressure (around the outside of port  290 ) plus backpressure from a fluidly connected upstream or downstream valve chamber residing up through the center of port  290 . 
         [0161]    Compliance chamber  286  as seen in  FIG. 73B  is configured a little bit differently and uses a portion of the membrane or sheeting seals  288  of valve chambers  282  and  284  to provide a compliant material covering a relatively large cross-sectional area  292  of chamber  286 . Here, a vacuum applied to sheeting  288  at chamber  286  negates the positive pressure Pc applied around the outside of ports  290  and expands the relatively large area  292  of the valve seal sheeting, pulling sheeting  288  down around the outside of port  290 . The configuration of  FIG. 73B  is advantageous in one respect because positive and negative pressures are applied to the same side of the cassette at chamber configuration  280 , such that associated pneumatics can be located on a single side of the cassette. 
         [0162]    By changing the pressure seen at compliance chamber  286  from a positive pressure when the valve chambers  282  and  284  are open to a negative value after the valve chambers results in that only the liquid side center of the volcano port  290  is exposed to high positive pressure. The liquid annular area of valve chambers  282  and  284  on the outside of volcano ports  290  sees the applied vacuum, which allows the air sealing pressure on the outside of the cassette to seal against backpressures that would have otherwise forced it open. This allows valve chambers  282  and  284  to seals well in both upstream and downstream configurations. 
         [0163]    In one example, suppose the total seal area of valve chambers  282  and  284  is one square inch and that the sealing area at the top of volcano port  290  is 0.1 square inch over the volcano. A positive ten psig air pressure would then apply an external force of 10 lbs to the entire valve chamber  282  or  284 . A backpressure on the annular fluid side of the associated port  290  from the applied ten psig pressure plus a backpressure the backpressure up through the center of port  290  from a downstream sealed valve would exert almost the same opposite “unsealing” force of ten pound (only difference would be the small annular area of port  290  at the top, which is a function of the port wall thickness and the diameter of the tube), resulting in a potentially leaky valve chamber  282  or  284 . A higher positive pressure, e.g., twenty psig, could be applied to valve chamber  282  or  284  forcing sheeting  288  to seal to port  290  against the 10 psig backpressure, however, the noise generated to create the twenty psig air pressure could objectionable to the user. There would also be no redundancy in the different valve pressures. 
         [0164]    Back to back valve chambers  282  and  284  of  FIGS. 73A and 73B , on the other hand, separated by an applied negative pressure, e.g., 5 psig vacuum, both seal independently well. The ten psig air pressure would still apply 10 lbs external force to seal both valves  282  and  284 , however, the 10 psig pressure at the center of the volcano port  290  and the −5 psig pressure on the annular area around the volcano would apply a total pressure of ten psig*0.1 sq in +(−5 psig)*0.9 sq in =−3.5 lbs. The net force to close the valve would be 13.5 lbs so that valve would seal very well. 
         [0165]    It may be possible to not use a separate vacuum and instead rely on the expansion of the flexible part of the compliance chamber  286  to absorb energy from the backpressure from one valve chamber  282  or  284  applied to the other valve chamber  282  or  284 . Here, apertures  283  allow the pressurized fluid inside chambers  282  and  284  and around ports  290  to communicate with fluid inside compliance chamber  286  and expand diaphragm  289  or sheeting area  292 , allowing the backpressure around ports  290  to dissipate. 
         [0166]    Valves V-DI-PRE, CK-PRE, V-DI-VEN and CK-VEN in  FIG. 52  (and other flow schematics) and valve chambers  282  and  284  of valve configuration  280  of cassette  40  shown in  FIG. 74  are constructed as shown schematically in  FIGS. 73A and 73B  and can seal against higher pressure in either direction. That is, not only does compliance chamber  286  serve to not disrupt an existing upstream or downstream first valve chamber closure when a second valve chamber in fluid communication with the first valve chamber is opened, compliance chamber  286  also aids in the closure of a first valve chamber when a second valve chamber in communication with the first valve chamber (upstream or downstream) has been closed previously, which could otherwise create positive fluid pressure against which the closure of the first valve chamber would have to fight. 
         [0167]      FIG. 75  illustrates that system  10  in one embodiment includes a wide pump head  22  that drives two dialysate pump segments  44  to mix two solutions in a ratio that is approximately equal to the ratio of the tube inside diameters squared (mix ratio=(ID 1 /ID2) 2 ), assuming the wall thicknesses of tubes  44  is the same. For a 1:1 mix ratio, consecutive segments of tubing from the same roll of tubing can be taken to provide segments of the same wall thickness and good mixing accuracy. Mixing accuracy is optimized because the inlet pressure on the supply lines is controlled within about four inches of water column by the bag manager, the tubing inner diameter is controlled during the manufacture of the disposable set, the pump race diameters are the same and the pump actuator rotational speed is the same for the parallel tubing segments. System  10  also ensures that an initial supply fluid temperature of each of the different dialysis fluids in tubes  44  is within a few degrees of each other. 
         [0168]    It should be understood that various changes and modifications to the presently preferred embodiments described herein will be apparent to those skilled in the art. Such changes and modifications can be made without departing from the spirit and scope of the present subject matter and without diminishing its intended advantages. It is therefore intended that such changes and modifications be covered by the appended claims.