PATENT DOCUMENT

Abstract:
A disposable fluid circuit kit for extracorporeal blood treatment systems that supply replacement fluid to a patient is described. The circuit has a blood portion that carries blood and subjects it to some treatment, such as dialysis or hemofiltration. A portion carries filtrate or dialysate. A replacement fluid portion that carries fluid used to compensate for fluid loss is connectable to a supply of replacement fluid. a sterilizing filter in the replacement fluid portion sterilizes the replacement fluid before introduction into the patient acting as a guard against touch contamination of the connected replacement fluid container. Preferably, the filter has a pore size effective to eliminate pyrogens.

Full Description:
RELATED APPLICATIONS 
     This application is a divisional of U.S. patent application Ser. No. 09/513,910, filed Feb. 25, 2000, entitled “Blood Treatment Systems and Methods That Maintain Sterile Extracorporeal Processing Conditions”, now U.S. Pat. No. 6,830,553, which is a divisional of U.S. patent application Ser. No. 09/451,238, filed Nov. 29, 1999, now abandoned. 
    
    
     Each of the following United States applications is hereby incorporated by reference as if fully set forth in its entirety herein:
         1. U.S. patent application Ser. No. 08/800,881, filed Feb. 14, 1997, and entitled “Hemofiltration System,” now abandoned;   2. U.S. patent application Ser. No. 09/451,238, filed Nov. 29, 1999, and entitled “Systems and Methods for Performing Frequent Hemofiltration,” now abandoned;   3. U.S. patent application Ser. No. 09/513,902, filed Feb. 25, 2000, and entitled “Layered Fluid Circuit Assemblies and Methods For Making Them;”   4. U.S. patent application Ser. No. 09/513,910, filed Feb. 25, 2000, and entitled “Hemofiltration Systems and Methods that Maintain Sterile Extracorporeal Processing Conditions;”   5. U.S. patent application Ser. No. 60/438,567 filed Jan. 7, 2003 entitled “Preparing Replacement Fluid By Means of Batch Filtration Prior to Treatment;”   6. U.S. Patent Application Ser. No. 60/386,483 filed Jun. 6, 2002 entitled “Last-Chance Quality Check and/or Air/Pathogen Filter for Infusion Systems;”   7. U.S. patent application Ser. No. 09/907,872, filed Jul. 17, 2001 entitled “Method and Apparatus for Manufacturing Filters;”   8. U.S. patent application Ser. No. 10/393,209 filed Mar. 20, 2003 entitled “Blood Circuit with Leak-Safe Features;” and   9. U.S. patent application Ser. No. 10/393,185 filed Mar. 20, 2003 entitled “Dual Access Spike for Infusate Bags.”       

     FIELD OF THE INVENTION 
     This invention relates to systems and methods for processing blood, e.g., for filtration, pheresis, or other diagnostic or therapeutic purposes. 
     BACKGROUND OF THE INVENTION 
     There are many types of continuous and intermittent blood processing systems, each providing different therapeutic effects and demanding different processing criteria. 
     For example, hemofiltration emulates normal kidney activities for an individual whose renal function is impaired or lacking. During hemofiltration, blood from the individual is conveyed in an extracorporeal path along a semipermeable membrane, across which a pressure difference (called transmembrane pressure) exists. The pores of the membrane have a molecular weight cut-off that can thereby pass liquid and uremic toxins carried in blood. However, the membrane pores can not pass formed cellular blood elements and plasma proteins. These components are retained and returned to the individual with the toxin-depleted blood. Membranes indicated for hemofiltration are commercially available and can be acquired from, e.g., Asahi Medical Co. (Oita, Japan). 
     After hemofiltration, fresh physiologic fluid is supplied to toxin-depleted blood. This fluid, called replacement fluid, is buffered either with bicarbonate, lactate, or acetate. The replacement fluid restores, at least partially, a normal physiologic fluid and electrolytic balance to the blood. Usually, an ultrafiltration function is also performed during hemofiltration, by which liquid is replaced in an amount slightly less than that removed. Ultrafiltration decreases the overall fluid level of the individual, which typically increases, in the absence of ultrafiltration, due to normal fluid intake between treatment sessions. 
     Following hemofiltration, fluid balancing, and ultrafiltration, the blood is returned to the individual. 
     SUMMARY OF THE INVENTION 
     The invention provides hemofiltration systems and methods that circulate blood from an individual through a hemofilter to remove waste and to return blood and replacement fluid to the individual after removal of waste. The systems and methods maintain sterile extracorporeal processing conditions during and between therapy sessions. 
     According to one aspect of the invention, the systems and methods include a waste discharge path in the extracorporeal circuit to convey waste fluid to a waste receiving unit. The waste discharge path includes an air break. The air break prevents back flow of waste contaminants into the extracorporeal circuit from the waste receiving unit. 
     According to another aspect of the invention, the systems and methods include a replacement fluid path in the extracorporeal circuit to convey replacement fluid from a source to the extracorporeal circuit. The replacement fluid path includes a sterilizing filter to avoid contamination of the extracorporeal circuit. 
     Another aspect of the invention provides a hemofiltration system and method employing a hemofiltration machine including a chassis and at least one flow controlling element on the chassis. An extracorporeal circuit is provided for circulating blood from an individual through a hemofilter to remove waste and to return blood to the individual after removal of waste. A portion of the extracorporeal circuit is integrated, at least in part, within a flexible panel free of an air-fluid interface. A fluid processing cartridge orients the flexible panel for mounting as an integrated unit on the chassis with the flexible panel in operating engagement with the flow controlling element and for removal as an integrated unit from the chassis. A controller for the hemofiltration machine is operable in a hemofiltration mode to operate the flow controlling element, when the fluid processing cartridge is mounted on the chassis, to convey an individual&#39;s blood through the extracorporeal fluid circuit to a hemofilter to remove waste fluid and to supply replacement fluid. The controller is also operable in a dwell mode to suspend the hemofiltration mode and retain the fluid processing cartridge on the chassis between multiple intermittent hemofiltration sessions during a prescribed time period. 
     In one embodiment, during the dwell mode, the controller operates the flow controlling element to introduce a bacteriostatic agent into the extracorporeal circuit. 
     In one embodiment, during the dwell mode, the controller subjects the extracorporeal circuit to refrigeration. 
     In one embodiment, the controller registers use of the extracorporeal circuit and prevents operation of the hemofiltration machine when the registered use fails to correlate with predetermined criteria. 
     Other features and advantages of the inventions are set forth in the following specification and attached drawings. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  is a diagrammatic view of a system that enables frequent hemofiltration by supplying to a treatment location a durable hemofiltration machine, a disposable fluid processing cartridge that fits on the machine, ancillary processing materials that the machine and cartridge use, and telemetry that supports the hemofiltration therapy; 
         FIG. 2  is a front perspective view of a hemofiltration machine that the system shown in  FIG. 1  supplies to a treatment location; 
         FIGS. 3 to 5  are side elevation views showing the loading into the machine shown in  FIG. 2  of a fluid processing cartridge, which the system shown in  FIG. 1  also supplies to the treatment location; 
         FIG. 6A  is a perspective view of the inside of the door of the hemofiltration machine shown in  FIG. 2 ; 
         FIG. 6B  is a side section view of a spring loaded pump race carried on the door shown in  FIG. 6A , taken generally along line  6 B- 6 B in  FIG. 6A ; 
         FIG. 7  is an exploded perspective view of one embodiment of the fluid processing cartridge that is supplied to the treatment location, comprising a tray in which a fluid processing circuit is contained; 
         FIG. 8  is an assembled perspective view of the fluid processing cartridge shown in  FIG. 7 ; 
         FIG. 9  is a side section view of the fluid processing cartridge shown in  FIGS. 7 and 8 , showing the cartridge as it is supplied in a closed, sterile condition to the treatment location; 
         FIG. 10  is a perspective view of the cartridge shown in  FIGS. 7 to 9 , in preparation of being mounted on the hemofiltration machine shown in  FIG. 2 ; 
         FIG. 11  is an embodiment of a fluid circuit that the cartridge shown in  FIG. 10  can incorporate, being shown in association with the pumps, valves, and sensors of the hemofiltration machine shown in  FIG. 2 ; 
         FIGS. 12A and 12B  are largely schematic side section views of one embodiment of fluid balancing compartments that can form a part of the circuit shown in  FIG. 11 , showing their function of volumetrically balancing replacement fluid with waste fluid; 
         FIGS. 13A ,  13 B, and  13 C are perspective views of a bag configured with a pattern of seals and folded over to define a overlaying flexible fluid circuit that can be placed in a fluid processing cartridge of a type shown in  FIG. 11 ; 
         FIG. 14  is a plane view of the pattern of seals that the bag shown in  FIGS. 13A ,  13 B, and  13 C carries, before the bag is folded over on itself; 
         FIG. 15  is a plane view of the overlaying fluid circuit that the bag shown in  FIG. 14  forms after having been folded over on itself; 
         FIG. 16  is a largely schematic side section view of the overlaying fluid balancing compartments that are part of the circuit shown in  FIG. 15 , showing their function of volumetrically balancing replacement fluid with waste fluid; 
         FIG. 17  is a front perspective view of an embodiment of a chassis panel that the hemofiltration machine shown in  FIG. 2  can incorporate; 
         FIG. 18  is a back perspective view of the chassis panel shown in  FIG. 17 , showing the mechanical linkage of motors, pumps, and valve elements carried by the chassis panel; 
         FIG. 19  is a diagrammatic view of a telemetry network that can form a part of the system shown in  FIG. 1 ; 
         FIG. 20  is a diagrammatic view of overlays for imparting control logic to the machine shown in  FIG. 2 ; 
         FIG. 21  is an embodiment of a set for attaching multiple replacement fluid bags to the cartridge shown in  FIG. 10 , the set including an in-line sterilizing filter; 
         FIG. 22  is a plane view of a graphical user interface that the hemofiltration machine shown in  FIG. 2  can incorporate; and 
         FIG. 23  is a perspective view of a generic user interface which can be customized by use of a family of interface templates, which the hemofiltration machine shown in  FIG. 2  can incorporate. 
     
    
    
     The invention may be embodied in several forms without departing from its spirit or essential characteristics. The scope of the invention is defined in the appended claims, rather than in the specific description preceding them. All embodiments that fall within the meaning and range of equivalency of the claims are therefore intended to be embraced by the claims. 
     DESCRIPTION OF THE PREFERRED EMBODIMENTS 
     The various aspects of the invention will be described in connection with providing hemofiltration. That is because the features and advantages that arise due to the invention are well suited to the performance of hemofiltration. Still, it should be appreciated that the various aspects of the invention can be applied to achieve other blood processing objectives as well, such as hemodialysis and hemopheresis. 
     I. System for Providing Frequent Hemofiltration 
       FIG. 1  shows a system  10  that makes it possible for a person whose renal function is impaired or lacking, to receive convenient and therapeutically effective hemofiltration on a frequent basis, e.g., at least four times weekly and, preferably, six times weekly. The frequent hemofiltration therapy that the system  10  provides has as one of its objectives the maintenance of uremic toxin levels in the person&#39;s blood within a comfortable range, e.g., at no more than 80% of the maximum level. Through frequent hemofiltration, the system  10  can provide either acute or chronic treatment of renal impairment or failure. 
     The system  10  delivers the durable and disposable equipment and materials necessary to perform frequent hemofiltration on the person at a designated treatment location  12 . 
     The location  12  can vary. It can, for example, be a setting where support and assistance by one or more medically trained care givers are immediately available to the person, such as at a hospital, an outpatient clinic, or another treatment center. Alternatively, the location  12  can comprise a setting where support or assistance is provided by a trained partner, such as in the person&#39;s residence. 
     By careful design of durable and disposable equipment, the system  10  can make it possible for the person to perform frequency hemofiltration in a non-clinical setting, without direct assistance from technically or medically trained persons. 
     To make frequent hemofiltration more convenient, the person preferably has been fitted with one or more vascular access devices  14 . Each device  14 , for example, may be generally constructed in the manner disclosed in pending U.S. patent application Ser. No. 08/724,948, filed Nov. 20, 1996, and entitled “Subcutaneously Implanted Cannula and Method for Arterial Access.” 
     The devices  14  preferably support high blood flow rates at or above 300 ml/min and preferably at least 600 ml/min. The devices  14  also enable quick and frequent cannulation. The devices  14  thereby reduce the time required to set up, perform, and complete a frequent hemofiltration session. The high blood flow rates that the devices  14  support also increase the removal rate of uremic toxins during hemofiltration, as will be described in greater detail later. 
     To enable frequent hemofiltration, the system  10  supplies to the treatment location  12  a durable hemofiltration machine  16 . The system  10  also supplies fluid processing cartridges  18  to the treatment location  12 , for installation on the machine  16  at the time of treatment. The system  10  further supplies ancillary materials  20 , such as replacement fluids, to the treatment location  12  for use in association with the cartridge  18  and machine  16 . The system  10  also preferably supplies a telemetry network  22 , to enable centralized, off-site monitoring and supervision of the frequent hemofiltration treatment regime. 
     The operation of the system  10  to provide these various functions will now be described in greater detail. 
     A. Supplying a Hemofiltration Machine 
     The system  10  includes a source  24  that supplies a hemofiltration machine  16  (which can also be called a “cycler”) to the treatment location  12 . The machine  16  is intended to be a durable item capable of long term, maintenance free use. 
       FIG. 2  shows a representative embodiment of a machine  16  capable of performing frequent hemofiltration. The machine  16  is preferably lightweight and portable, presenting a compact footprint, suited for operation on a table top or other relatively small surface normally found, e.g., in a hospital room or in a home. The compact size of the machine  16  also makes it well suited for shipment to a remote service depot for maintenance and repair. 
     In the illustrated embodiment, the machine  16  includes a chassis panel  26  and a panel door  28  that moves on a pair of rails  31  in a path toward and away from the chassis panel  26  (as shown by arrows in  FIG. 2 ). A slot  27  is formed between the chassis panel  26  and the door  28 . As  FIGS. 3 to 4  show, when the door  28  is positioned away from the panel  26 , the operator can, in a simple vertical motion, move a fluid processing cartridge  18  into the slot  27  and, in a simple horizontal motion, fit the cartridge  18  onto a raised portion of the chassis panel  26 . When properly oriented, the fluid processing cartridge  18  rest on the rails  31  to help position the cartridge  18 . As  FIG. 5  shows, movement of the door  28  toward the panel  26  engages and further supports the cartridge  18  for use on the panel  26  for use. This position of the door  28  will be called the closed position. 
     The machine  16  preferably includes a latching mechanism  30  and a sensor  32  (see  FIG. 2 ) to secure the door  28  and cartridge against movement before enabling circulation of fluid through the cartridge  18 . 
     As will be described in greater detail later, the processing cartridge  18  provides the blood and fluid interface for the machine  16 . 
     The machine  16  pumps blood from the person, through the fluid processing cartridge  18  to a hemofilter  34  (mounted in brackets to the side of the chassis panel  26 , as shown in phantom lines in  FIGS. 2 to 5 ), back to the cartridge  18 , and then back to the person. 
     Alternatively, the hemofilter  34  can form an integrated part of the cartridge  18 . The hemofilter  34  is connected via the cartridge  18  to the person&#39;s blood supply through the vascular access devices  14 . 
     The machine  16  includes a blood handling unit  36  mounted on the chassis panel  26 . The blood handling unit  36  includes a peristaltic blood pump  92  and various clamping and sensing devices(described later). The blood handling unit  36  circulates the person&#39;s blood in a controlled fashion through the hemofilter  34  and back to the person. The hemofilter  34  removes waste fluid containing urea and other toxins. 
     The machine  16  also includes a fluid management unit  38  mounted on the chassis panel  26 . The fluid management unit  38  includes a peristaltic waste and replacement fluid pump  152  and various clamping and sensing devices(described later). The fluid management unit  38  replaces the waste fluid with a sterile replacement fluid, for return with the treated blood to the person&#39;s blood supply. The replacement fluid also acts to maintain the person&#39;s electrolytic balance and acid/base balance. 
     The fluid management unit  38  includes a fluid balancing element  40  mounted on the chassis panel  26 . The fluid balancing element  40  meters the return replacement fluid in proportion to the amount of waste fluid removed. 
     In the illustrated embodiment, the fluid balancing element  40  includes one or more balancing chambers  206 ,  208  and associated clamping devices(the details of which will be described later). The chambers  206 ,  208  comprise preformed depressions formed in the raised portion of the chassis panel  26 . As  FIG. 6A  shows, preformed depressions on the door  28  form mating chambers  206 ′,  208 ′, which register with the chassis panel chambers  206 ,  208 . When the door  28  is closed, the registered chambers  206 / 206 ′ and  208 / 208 ′ define between them spaces of known volume, e.g., 20 ml. The known volume can, of course, be greater or less than 20 ml, and the chambers  206 / 206 ′ and  208 / 208 ′ can each have a different known volume. 
     As will be described in greater detail later, flexible containers  212  and  214 , which form a part of a preformed fluid circuit carried within the fluid processing cartridge  18 , fit into the registered chambers  206 / 206 ′ and  208 / 208 ′. The chambers  206 / 206 ′ and  208 / 208 ′ and associated clamping devices interact with the containers  212  and  214 , to provide the capability of balancing waste and replacement fluid volumetrically, in an accurate, straightforward manner, without use of weigh scales and weight sensing. 
     The machine  16  also includes an ultrafiltration unit  42  on the chassis panel  26 . The ultrafiltration unit  42  includes a peristaltic ultrafiltration pump  144  to remove additional waste from the person without addition of replacement fluid. The machine  16  provides, at the end of each frequent hemofiltration session, a net ultrafiltration fluid loss, which coincides with an amount prescribed by the attending physician. 
     The machine  16  completes a frequent hemofiltration session when a prescribed replacement fluid volume has been exchanged and the net ultrafiltration fluid loss target has been met. The machine  16  can accommodate continuous or extended treatment sessions on an automated basis. The machine  16  can also accommodate operation based upon individually set ultrafiltration rates, blood flow rates, or return fluid flow rates, with completion determined by the volume of replacement fluid exchanged or by a treatment timer. 
     As will be described in greater detail later, the various pumping, clamping, and sensing devices on the machine  16  provide blood flow, fluid management, and safety functions by sensing pump pressures, detecting air, detecting blood leak through the hemofilter  34 , and sensing waste pressure. The sensors also provide addition fluid management and safety functions, such as sensing replacement fluid temperature and replacement fluid pump pressure. The machine  16  also provides other processing functions, such as priming, supplying a replacement fluid bolus, and carrying out a rinseback of the person&#39;s blood. 
     The machine  16  also preferable includes an operator interface  44 , which, in the illustrated embodiment (see  FIG. 2 ) is carried on the exterior of the door  28 . As will be described later, the interface  44  provides simple switch and/or knob operation of the machine  16 , preferably by use of one hand. The interface  44  displays information necessary to operate the machine  16 , presenting an uncluttered display and tactile touch buttons to intuitively lead a person without technical or medical background through set up and operation of the machine  16  with a minimum of training. 
     Further details of the machine  16 , the pumps and sensing devices, and their interaction with the fluid processing cartridge  18  will be described later. 
     The source  24  supplying the machine  16  can comprise a company or business that manufactures the machine  16  or otherwise distributes the machine  16  to the treatment location  12  on a sale, lease, or rental basis. 
     B. Supplying a Fluid Processing Cartridge 
     The system  10  further includes a source  46  for supplying a fluid processing cartridge  18  to the treatment location  12  for use in association with the machine  16 . The cartridge  18  is intended to be disposable item, capable of single or extended use, which the loads on the machine  16  before beginning a hemofiltration session (as  FIGS. 3 to 5  show). The cartridge  18  can be removed from the machine  16  and discarded upon the completing the hemofiltration session, or its use can be extended to one or more subsequent sessions, as will be described later. 
     The cartridge  18  couples to the person&#39;s vascular access devices  14  and interacts with the machine  16  to draw, process, and return blood in a continuous, extracorporeal path, to carry out fluid balancing through waste removal, replacement fluid exchange, and ultrafiltration. 
     Preferably, the tasks of loading and unloading the cartridge  18  are simple and straightforward, following a simple, straight loading and unloading path into the slot  27  and against the chassis panel  26 , as  FIGS. 3 to 5  show. In this way, the person receiving hemofiltration can by himself/herself set up the cartridge  18  and machine  16 , without necessarily requiring assistance from a technically or medically trained person. 
     The cartridge  18  preferably provides the entire blood and fluid interface for the machine  16 , including all pumping, valving, pressure sensing, air detection, blood leak detection, and tubing management. The cartridge  18  preferable is supplied to the treatment location  12  with all tubing, access needles and waste and replacement fluid connections preconnected. A waste bag also can be preattached, if desired, or the waste line can be placed in a drain. 
     Loading the cartridge  18  on the chassis panel  26  and closing the door  28  also automatically locates all sensors of the machine&#39;s safety function in association with the blood fluid interface. The operator is not required to load anything else to carry out the machine&#39;s safety function. Once the machine  18  undergoes start up testing to confirm cartridge placement and integrity and to confirm the functionality of the sensors, subsequent automated operation the machine  18  in a safe mode is assured. 
     The cartridge  18  can be constructed in various ways. In the illustrated embodiment (see  FIGS. 7 to 9 ), the cartridge  18  includes a preformed tray  48  and insert  53  manufactured, e.g., by thermoforming polystyrene or another comparable material. The tray  48  and insert  53  are peripherally joined together, e.g., by ultrasonic welding. 
     The tray includes a base  50 , side walls  52 , and an open top edge  54 . The geometry of the tray  48  is appropriately keyed to fit in only one orientation on the rails  31  in the slot  27  between the chassis panel  26  and door  28  of the machine  16 . When so fitted, the insert  53  rests on the raised portion of the chassis panel  26 . Closing the door  28  secures the tray  48  to the panel  26 . 
     A preformed circuit  56  is carried between the base  50  of the tray  48  and the insert  53 . The circuit  56  is arranged to carry blood, waste, and replacement fluid during hemofiltration. 
     As will be described in greater detail later, the circuit  56  includes an array of fluid flow paths formed with in-line flexible containers  212  and  214 (for fluid balancing), peristaltic pump headers, sensor stations, tubing, and valve stations. The layout of flow paths, containers, pump headers, sensing stations, and valve stations on the circuit  56  form a mirror image of the layout of the structural and mechanical components on the chassis panel  26  and door  28  of the machine  16 . 
     The insert  53  includes cut outs  58  to expose the containers, peristaltic pump headers, sensing stations, and valve stations for engagement with equipment on the chassis panel  26 . When the tray  48  is fitted to the chassis panel  26 , and the door  28  is closed, the in-line containers  212 / 214  formed in the circuit  56  fit within the registered chambers  206 / 206 ′ and  208 / 208 ′ on the chassis panel  26  and door  28 . Likewise, the pump headers and the sensor and valve stations on the circuit  56  overlay and engage corresponding peristaltic pumps, sensors, and valve on the chassis panel  26 . 
     In the illustrated embodiment (see  FIG. 7 ), the base  50  of the tray  48  underlaying the pump stations is relieved, to form pump races  360 . The inside surface of the door  28  carries concave pump races  362  supported by springs  364 (see  FIGS. 6A and 6B ). When the door  28  is closed, the spring loaded pump races  362  on the door  28  nest with the relieved pump races  360  on the tray  48 , to provide rigidity and support. Alternatively, the pump races  360  can form cutouts in the base  50  (like cut outs  58  in the insert, as earlier described), through which the pump races  362  on the door  28  extend. 
     The base  50  of the tray  48  underlying the containers  212 / 214  is also relieved, to form chamber supports  368 . When the door  28  is closed, the tray supports  368  fit within the door chambers  206 ′ and  208 ′. The door  28  therefore engages the tray  48 , to add overall rigidity and support to the tray base  50 . 
     When the door  28  is closed, the containers  212 / 214  are enclosed within the registered chambers  206 / 206 ′ and  208 / 208 ′ and tray chamber supports  368 , which define for the containers  212 / 214  to a known maximum volume. The peristaltic pumps, sensors, and valve stations on the machine  16  interact with the flexible components of the circuit  56 . 
     The cartridge  18  makes possible direct, centralized connection of a blood-fluid interface to the blood pump, the waste and replacement pump, the ultrafiltration pump, the fluid balancing chambers, the sensor devices, and the clamping devices of the machine  16 , with no air interfaces. The compact arrangement of the cartridge  18  also reduces fluid pressure drops, thereby accommodating high flow rates, e.g., an arterial blood line pressure drop of less than 250 mmHg at a flow rate of 600 ml/min and a hematocrit of 25. 
     As  FIGS. 9 and 10  show, lengths of flexible tubing FT are coupled to the circuit  56  in the base  50  of the tray  48  and rest in coils on top of the insert  53  within the tray  48  during shipment and before use (see  FIG. 9 ). As  FIG. 9  also shows, a removable lid  60 , made, e.g., from ethylene oxide permeable TYVEK™ material or polyethylene plastic sheet stock, covers and seals the interior of the tray  48  prior to use. The cartridge  18  can therefore be sterilized by exposure to ethylene oxide prior to use. Other methods of sterilization, e.g., gamma radiation or steam sterilization, can be used. Alternatively, the ultrasonically welded assembly of the tray  58 , insert  53 , and the circuit  56  (with attached tubing FT) can be packaged as a unit into a sealed plastic bag for sterilization, obviating the need for the lid  60 . 
     At the instant of use, the lid  60  is peeled away, or, in the alternative arrangement, the sealed plastic bag is opened. The attached flexible tubing FT is extended beyond the bounds of the tray  48  to make connection with external processing items (see  FIG. 10 ). The tubing FT carries appropriate couplers for this purpose. The tray  48  is moved along a vertical path for loading into the slot  27  and then a horizontal path for loading on the raised portion of the chassis panel  26 , after which a simple motion of the door latching mechanism  30  aligns the entire fluid circuit  56  with the pumps, sensors, and clamps on the chassis panel  26 . There is no area of blood or fluid contact that this outside the disposable circuit  56 . 
     The source  46  supplying the cartridge  18  can comprise a company or business that manufactures the cartridge  18  or that otherwise distributes the cartridge  18  to the treatment location  12  on a sale, lease, or rental basis. 
     1. Fluid Circuit for Frequent Hemofiltration 
       FIG. 11  shows a representative fluid circuit  56  that is well suited for carrying out frequent hemofiltration, and which can be incorporated into the cartridge  18  for interface with pumps, valves, and sensors arranged as a mirror image on the chassis panel  26 . 
     The fluid circuit  56  couples the hemofilter  34  to several main fluid flow paths. The main fluid flow paths comprise an arterial blood supply path  62 , a venous blood return path  64 , a blood waste path  66 , a replacement fluid path  68 , and an ultrafiltration/fluid balancing path  70 . 
     (i) Blood Supply and Return Paths 
     The arterial blood supply path  62  and venous blood return path  64  includes lengths of flexible tubing  72  and  74  that extend outside the tray  48  (see  FIG. 10 ). As  FIG. 10  shows, The paths  72  and  74  carry cannulas  76  at their distal ends (or connectors that enable connection to cannulas  76 ), to enable connection, respectively, to the person&#39;s arterial and venous access devices  14 . 
     The arterial blood supply path  62  also includes a length of flexible tubing  78  (see  FIG. 10 ) that extends outside the tray  48 . The tubing  78  includes a distal connector  80  to couple to the blood inlet  82  of the hemofilter  34 . 
     Likewise, the venous blood return path  64  includes a length of flexible tubing  84  that extends outside the tray  48 . The tubing  84  includes a distal connector  86  to couple to the blood outlet  88  of the hemofilter  34 . 
     Alternatively, the hemofilter  34  can be an integral part of the tray  48 . In this arrangement, the arterial and venous blood paths  78  and  84  are supplied pre-connected to the hemofilter  34 . 
     The exterior tubing components of the arterial or venous blood paths can include injection sites  90 . The sites can be used, e.g., to remove trapped air or to inject anticoagulant, medication, or buffers into the blood flows. The exterior tubing components of the arterial or venous blood paths can also include conventional pinch clamps, to facilitate patient connection and disconnection. 
     The remaining portions of arterial and venous blood paths  62  and  64  are contained in the circuit  56  held within the tray  48 . The blood pump  92  of the machine  16  engages a pump header region  94  in the arterial blood supply path  62  within the tray  48  upstream of the hemofilter  34 , to convey blood into and through the hemofilter  34 . An arterial blood clamp  96  and a patient connection-disconnection (air bubble detector) sensor  98  on the machine  16  engage a clamp region  100  and a sensor region  102  in the arterial blood supply path  62  within the tray  48  upstream of the blood pump  92 . Alternatively, an air bubble sensor (not shown) can be located downstream of the blood pump  92  and upstream of the hemofilter  34 . 
     The placement of the air sensor  98  upstream of the hemofilter  34  allows air bubbles to be detected prior to entering the hemofilter  34 . In the hemofilter  34 , air bubbles break up into tiny micro-bubbles, which are not as easily detected. Placement of the air sensor  98  upstream of the hemofilter  34  also serves the additional purpose of detecting air when the blood pump  92  is operated in reverse, to rinse back blood to the patient, as will be described later. 
     An air detector  108  on the machine  16  engages a sensing region  110  in the venous blood return path  64  within the tray  48  downstream of the hemofilter  34 . A venous clamp  112  on the machine  16  engages a clamp region  114  in the venous blood return path  64  within the tray  48  downstream of the air detector  108 . 
     (ii) Blood Waste Path 
     The membrane (not shown) located in the hemofilter  34  separates waste including liquid and uremic toxins from the blood. A waste outlet  116  conveys waste from the hemofilter  34 . 
     The blood waste path  66  includes a length of flexible tubing  118  (see  FIG. 10 ) that extends beyond the tray  48 . The tubing  118  carries a distal connector  120  to couple to the waste outlet  116  of the hemofilter  34 . Alternatively, when the hemofilter  34  is integrated in the tray  48 , the waste path  66  can be supplied pre-connected to the hemofilter  34 . 
     The waste path  66  also includes a length of flexible tubing  122  that extends beyond the tray  48 . The tubing  122  carries a connector  124  to couple to a waste bag  126  or an external drain. Alternatively, the waste bag  126  can be preconnected to the tubing  122 . 
     The remainder of the waste path  66  is contained within the circuit  56  inside the tray  48 . A blood leak detector  128  on the machine  16  engages a sensor region  130  in the waste path  66  downstream of the hemofilter  34 . A waste pressure sensor  132  on the machine  16  engages another sensor region  134  in the waste path  66  downstream of the blood leak detector  128 . 
     Within the tray  48 , the waste path  66  branches into an ultrafiltration path  136  and a balancing path  138 . The ultrafiltration branch path  136  bypasses in-line containers  212  and  214  of the circuit  56 . The ultrafiltration pump  144  on the machine  16  engages a pump header region  146  in the ultrafiltration branch path  136  within the tray  48 . The waste balancing branch path  138  communicates with the in-line containers  212  and  214 . The waste and replacement fluid pump  152  on the machine  16  engages a pump header region  154  in the waste balancing branch path  138  within the tray  48  upstream of the in-line containers  212  and  214 . A pressure sensor  156  on the machine  16  engages a sensor region  160  in the waste balancing branch path  138  within the tray  48  between the waste and replacement fluid pump  152  and the in-line containers  212  and  214 . The pressure sensor  156  senses the fluid pressure required to convey replacement fluid into the venous return line. This resistance to the flow of replacement fluid is the venous blood pressure. The pressure sensor  156  in the waste fluid path  138  thereby serves to sense the venous blood pressure. 
     A flush clamp  162  engages a clamp region  164  in the waste path  66  within the tray  48  downstream of the in-line containers  212  and  214 . A waste clamp  166  engages a clamp region  168  in the waste path  66  downstream of the flush clamp  162 . The circuit  56  in the tray  48  also can include an air break  170 , which communicates with the waste path  66  downstream of the waste clamp  166 . The air break  170  prevents back flow of contaminants into the circuit  56  from the waste bag  126  or drain. 
     (iii) Replacement Fluid Path 
     The replacement fluid path  68  includes a length of flexible tubing  172  that extends outside the tray  48 . The tubing  172  includes a distal connector  174  or connectors that enable connection to multiple containers of replacement fluid  176 . As will be described later, the tubing  172  can also include an in-line 0.2 m sterilizing filter  178  to avoid contamination of the circuit  56 . 
     The containers  176  together typically hold from 8 to 20 combined liters of replacement fluid, depending upon the fluid removal objectives of the particular frequent hemofiltration procedure. The replacement fluid is also used to prime the fluid circuit  56  at the outset of a treatment session and to rinse back blood to the patient at the end of a treatment session. 
     The remainder of the replacement fluid path  68  is contained in the circuit  56  within the tray  48 . Sensing region  186  in the replacement fluid path  68  inside the tray  48  engages a replacement fluid flow rate detector  182  on the machine  16 . A clamping region  190  in the replacement fluid path  68  inside the tray  48  engages a replacement fluid clamp  188  on the machine  16 . 
     Within the tray  48 , the replacement fluid path  68  includes a priming or bolus branch path  192  that communicates with the arterial blood supply path  62 . A clamping region  196  in the priming branch path  192  engages a priming clamp  194  on the machine  16 . 
     Within the tray  48 , the replacement fluid path  68  also includes a balancing branch path  198  that communicates with the venous blood return path  64 , via the in-line containers  212  and  214 . A pump header region  200  in the balancing replacement branch path  198  engages the waste and fluid replacement pump  152  on the machine  16  upstream of the in-line containers  212  and  214 . 
     In the illustrated embodiment, the waste and fluid replacement pump  152  comprises a dual header pump, simultaneously engaging the two pump header regions  154  and  200  on the waste path  66  and the replacement fluid path  68 . A sensor region  204  in the balancing replacement branch path  198  engages a pressure sensor  202  on the machine  16  between the waste and replacement fluid pump  152  and the in-line containers  212  and  214 . The pressure sensor  202  senses the pressure required to convey waste fluid into the waste return line. This resistance to the flow of waste fluid is the waste line pressure. The pressure sensor  202  in the replacement fluid path  198  thereby serves to sense the waste line pressure. Similarly, as already described, the pressure sensor  156  in the waste fluid path  138  serves to sense the venous blood pressure. 
     (iv) Ultrafiltration/Fluid Balancing Path 
     The ultrafiltration waste branch path  136  within the tray  48 , which bypasses the in-line containers  212  and  214  of the circuit  56 , accommodates transfer of a prescribed volume of waste to the waste bag  126 , without an offsetting volume of replacement fluid. The circuit  56  thereby is capable of performing an ultrafiltration function. 
     The balancing waste branch path  138  and the balancing replacement branch path  198  pass through the in-line containers  212  and  214  in the circuit  56  contained within the tray  48 . The in-line containers  212  and  214  transfer a volume of replacement fluid to the venous blood return path  64  in proportion to the volume of waste fluid removed, except for the volume making up the ultrafiltration volume loss. The circuit  56  is thereby capable of performing a fluid balancing function in addition to the ultrafiltration function. 
     In the illustrated embodiment, the machine  16  and circuit  56  carry out the fluid balancing function volumetrically, without weight sensing. More particularly, the registered chambers  206 / 206 ′ and  208 / 208 ′ on the chassis panel  26  and door  28  of the machine  16  receive the in-line containers  212  and  214  when the tray  48  is mounted on the chassis panel  26 . The registered chambers  206 / 206 ′ and  208 / 208 ′ mutually impose volumetric constraints on the in-line containers  212  and  214 , to define a maximum interior volume for each of the on-line containers  212  and  214 . In the illustrated embodiment, when facing the chassis panel  26 , the container  212  is situated on the left side (in registered chambers  206 / 206 ′) and the container  214  is situated on the right side (in registered chambers  208 / 208 ′).  FIGS. 12A and 12B  show one embodiment of the right and left orientation of the containers  212  and  214 , with the containers  212  and  214  also shown in side section. 
     In the embodiment shown in  FIGS. 12A and 12B , each in-line container  212  and  214  is itself divided along their midline from front to back by an interior flexible wall  210 , to form four compartments. As  FIG. 12A and 12B  show, two of the compartments face the door  28 , and are thus designated as front compartments  212 F and  214 F. The other two compartments face the chassis panel  26 , and will thus be designed as rear compartments  212 R and  214 R. 
     Each in-line container  212  and  214  has a waste side compartment communicating with waste path  66  and a replacement side compartment communicating with the replacement fluid path  68 . In the illustrated embodiment, the circuit  56  establishes communication between the balancing waste branch path  138  and the rear compartments  212 R and  214 R (which will also be called the waste side compartments). The circuit  56  also establishes communication between the balancing replacement branch path  198  and the front compartments  212 R and  214 R (which will also be called the replacement side compartments). In the embodiment illustrated in  FIGS. 12A and 12B , fluid enters the compartments from the bottom and exits the compartments from the top. Other flow paths into and from the compartments can be established, as will be described later. 
     The machine  16  includes an inlet valve assembly  216  and an outlet valve assembly  218  on the chassis panel  26 , located in association with the chambers  206  and  208 . The circuit  56  in the tray  48  likewise includes, for each in-line container  212  and  214 , an inlet clamp region  220  and an outlet clamp region  222 , which govern flow into and out of the waste side compartments  212 R and  214 R. The circuit  56  in the tray  48  also includes, for each in-line container  212  and  214 , an inlet clamp region  224  and an outlet clamp region  226 , which govern flow into and out of the replacement side compartments  212 F and  214 F. 
     When the tray  48  is mounted on the chassis panel  26 , the inlet and outlet valve assemblies  216  and  218  on the machine  16  engage the corresponding waste and replacement fluid inlet and outlet clamp regions  220 ,  222 ,  224 ,  226  in the circuit  56 . The machine  16  toggles the operation of inlet and outlet valve assemblies  216  and  218  to synchronize the flow of fluids into and out of the waste side and replacement side compartments of each in-line container  212  and  214 . 
     More particularly, for a given in-line container  212  and  214 , in a first valve cycle (see  FIG. 12A ), the waste side inlet valve  220  is opened while the waste side outlet valve  222  is closed. Waste fluid is conveyed by operation of the waste and replacement pump  152  from the waste path  66  into the waste side compartment of the given in-line container  212  and  214 . Simultaneously, for the same in-line compartment  212  and  214 , the replacement side inlet valve  224  is closed and the replacement side outlet valve  226  is opened, so that the incoming flow of waste in the waste side compartment displaces the interior wall  210  to express a like volume of replacement fluid from the replacement side compartment into the venous blood return path  64 . 
     In a subsequent cycle for the same in-line container  212  and  214 , an opposite valve action occurs (see  FIG. 12B ). The replacement side inlet valve  224  is opened and the replacement side outlet valve  226  is closed, and replacement fluid is conveyed into the replacement side compartment from the replacement fluid path  68 . The incoming replacement fluid displaces the interior wall  210  to express a like volume of waste fluid from the waste side compartment to the waste bag  126  (the waste side inlet valve  220  now being closed and the waste side outlet valve  222  now being opened). 
     As  FIGS. 12A and 12B  show, the valve assemblies work in tandem upon the two in-line containers  212  and  214 , with one container  140  receiving waste and dispensing replacement fluid, while the other container  142  receives replacement fluid and dispenses waste, and vice versa. In this way, the circuit  56  provides a continuous, volumetrically balanced flow of waste fluid to the waste bag  126  and replacement fluid to the venous blood return path  64 . 
     2. A Circuit Contained in a Double Panel Bag 
     The function of the fluid circuit  56  shown in  FIGS. 11 ,  12 A, and  12 B can be realized in various ways.  FIGS. 13A to 13C  show a fluid circuit bag  228  made from two overlaying sheets  230 A and  230 B of flexible medical grade plastic, e.g., poly vinyl chloride (see  FIG. 13A ). When laid flat (see  FIG. 13B ), the bag  228  defines first and second panels  232  and  234  divided along a midline  236 . By folding the bag  228  about its midline  236  (see  FIG. 13C ), the first and second panels  232  and  234  are brought into registration in a reverse facing relationship, with one panel  232  comprising the front of the bag  228  and the other panel  234  comprising the back of the bag  228 . 
     The first and second panel  232  and  234  each includes an individual pattern of seals S formed, e.g., by radio frequency welding. The seals S form fluid flow paths, including the in-line containers  212  and  214 , peristaltic pump header regions, the sensor regions, and clamp regions previously described. The flow paths formed by the pattern of seals S can comprise all or part of the circuit  56 . Pump header tubing lengths  155 ,  145 , and  201  are sealed in placed within the seal pattern S to form the pump regions  154 ,  146 , and  201 , respectively. 
     In the illustrated embodiment, as  FIG. 14  shows, the seals S on the first panel  232  are configured to form the flow paths of the circuit  56  through which replacement fluid is conveyed from the replacement fluid path  68  to the venous blood return path  64 , including the left and right front-facing replacement fluid compartments  212 F and  214 F. The seals S on the second panel  234  are configured to form the flow paths of the circuit  56  through which waste fluid is conveyed from the waste path  66  to the waste bag  126  or drain, including the left and right rear-facing waste fluid compartments  212 R and  214 R. Seals S form four individual containers, two containers  212 F and  214 F on the panel  232 , and two containers  212 R and  214 R on the panel  234 . 
     Once the seal patterns S are formed, the bag  228  is folded over about its midline  236  (see  FIG. 15 ). The bag  228  places in close association or registry the waste and replacement fluid paths  66  and  68  of the circuit  56 . The replacement fluid paths  68  of the circuit  56  occupy the front panel  232  of the bag  228 , and the waste paths  66  of the circuit  56  occupy the back panel  234  of the bag  228  (or vice versa, depending upon the desired orientation of the bag  228 ). 
     In use, the folded over bag  22 , 8  is contained in the base  50  of the tray  48 , with portions exposed through cutouts  58  in the insert  51  for engagement with the machine peristaltic pumps, sensing elements, and clamping elements, in the manner shown in  FIG. 10 . The remaining portions of the circuit  56  not contained within the bag  228  are formed of tubing and fit into preformed areas in the base  50  of the tray  48  (or formed within another bag) and coupled in fluid communication with the flow paths of the bag  228 , to complete the circuit  56  shown in  FIG. 10 . 
     The flow paths formed on the first panel  232  include the balance replacement fluid paths  198 , which lead to and from the replacement side compartments  212 F and  214 F. In the tray  48 , the replacement side compartments  212 F and  214 F rest in recesses in the tray base  50 . Cutouts  58  in the insert  51  expose the pump header regions  200  and  154 , to engage the peristaltic waste and replacement pump  152  on the machine  16 ; the inlet clamp regions  224 , to engage the inlet valve assembly  216  on the machine  16  to control inflow of replacement fluid into the replacement side compartments  212 F and  214 F; and the outlet clamp regions  226 , to engage the outlet valve assembly  218  on the machine  16  to control outflow of replacement fluid from the replacement side compartments  212 F and  214 F. The cutouts  58  also expose the sensor region  204 , to engage the pressure sensor  202  downstream of the waste and replacement pump  152 , and a pressure relief path  240  with exposed pressure relief bypass valve  242 , the purpose of which will be described later. A small opening  203  formed in the pump header tubing  201  opens communication with the relief path  240 . 
     The flow paths formed on the second panel  234  (shown in phantom lines in  FIG. 15 ) include the waste path  138  that lead to and from the waste side compartments  212 R and  214 R (for fluid balancing) and the waste path  136  that bypasses the waste side compartments  212 R and  214 R (for ultrafiltration). As  FIG. 15  shows, when the bag  228  is folded over in the tray  48 , the waste compartments  212 R and  214 R on the waste panel  234  and the replacement compartments  212 F and  214 F on the replacement panel  232  overlay, so both are exposed through the cutout  58  in the insert for registry as a unit with the chambers  206  and  208  on the chassis panel  26 . 
     The flow paths on the waste panel  234  also include the exposed waste inlet clamp regions  220 , to engage the valve assembly  218  to control inflow of waste fluid into the waste compartments  212 R and  214 R, and the exposed waste outlet clamp regions  222 , to engage the valve assembly  216  to control outflow of waste fluid from the waste compartments  212 R and  214 R. When the bag  228  is folded over in the tray  48 , the inlet clamp regions of the waste compartments  212 R and  214 R formed on the waste panel  234  overlay the outlet clamp regions of the replacement compartments  212 F and  214 F formed on the replacement panel  232 , and vice versa. 
     The flow paths also includes an exposed pump header region  154 , to engage the peristaltic waste and replacement pump  152 . When the bag  228  is folded over in the tray  48 , the exposed pump header regions  200  and  154  on the replacement and waste panels  232  and  234  lay side-by-side, to accommodate common engagement with the dual header waste and replacement pump  152 . The flow paths also include the sensor region  160 , to engage the pressure sensor  156  downstream of the waste and replacement fluid pump  152 . 
     The flow paths also include the pump header region  146 , to engage the peristaltic ultrafiltration pump  144 . When the bag  228  is folded over in the tray  48 , the exposed pump header region  146  for the ultrafiltration pump  144  is spaced away from the other pump header regions of the circuit  56 . 
     In  FIGS. 12A and 12B , the entry paths serving the waste and replacement compartments are located at the bottom, while the exit paths serving the waste and replacement compartments are located at the top. This configuration facilitates priming of the compartments. Still, the spaced apart configuration requires eight valve assemblies. 
     In  FIG. 16 , the entry and exit paths serving the waste and replacement compartments are all located at the top. Priming is still achieved, as the paths are top-oriented. Furthermore, due to the folded-over configuration of the bag itself, the clamping regions  220 ,  222 ,  226  can be arranged overlay one another. The overlaying arrangement of the clamping regions  220 ,  222 ,  224 , and  226  serving the waste and replacement compartments simplifies the number and operation of the inlet and outlet valve assemblies  216  and  218  on the machine  16 . Since the inlet clamp regions  224  for the replacement compartments  212 F and  214 F overlay the outlet clamp regions  222  for the waste compartments  212 R and  214 R, and vice versa, only four clamping elements  244 ,  246 ,  248 ,  250  need be employed to simultaneously open and close the overlaying eight clamp regions (see  FIG. 16 ). By further stacking (not shown) of the compartments, the clamping elements could be reduced to two. 
     As  FIG. 16  shows, the first clamping element  244  is movable into simultaneous clamping engagement with the inlet clamp region  224  of the left replacement compartment  212 F (on the replacement panel  232 ) and the outlet clamp region  222  of the left waste compartment  212 R (on the waste panel  234 ), closing both. Likewise, the fourth clamping element  250  is movable into simultaneous clamping engagement with the inlet clamp region  224  of the right replacement compartment  214 F (on the replacement panel  232 ) and the outlet clamp region  222  of the right waste compartment  214 R (on the waste panel  234 ), closing both. 
     The second clamping element  246  is movable into simultaneous clamping engagement with the outlet clamp region  226  of the left replacement compartment  212 F (on the replacement panel  232 ) and the inlet clamp region  220  of the left waste compartment  212 R (on the waste panel  232 ), closing both. Likewise, the third clamping element  248  is movable into simultaneous clamping engagement with the outlet clamp region  226  of the right replacement compartment  214 F(on the replacement panel  232 ) and the inlet clamp region  220  of the right waste compartment  214 R (on the waste panel  234 ), closing both. 
     The machine  16  toggles operation of the first and third clamping elements  244 ,  248  in tandem, while toggling operation the second and fourth clamping elements  246 ,  250  in tandem. When the first and third clamping elements  244 ,  248  are operated to close their respective clamp regions, replacement fluid enters the right replacement compartment  214 F to displace waste fluid from the underlying right waste compartment  214 R, while waste fluid enters the left waste compartment  212 R to displace replacement fluid from the overlaying left replacement compartment  212 F. When the second and fourth clamping elements  246 ,  250  are operated to close their respective clamp regions, replacement fluid enters the left replacement compartment  212 F to displace waste fluid from the underlying left waste compartment  212 R, while waste fluid enters the right waste compartment  214 R to displace replacement fluid from the overlaying right replacement compartment  214 F. 
       FIGS. 17 and 18  show a mechanically linked pump and valve system  300  that can be arranged on the chassis panel  26  and used in association with the layered fluid circuit bag  228  shown in  FIG. 15 . 
     The system  300  includes three electric motors  302 ,  304 , and  306 . The first motor  302  is mechanically linked by a drive belt  308  to the dual header waste and replacement pump  152 , previously described. The second motor  304  is mechanically linked by a drive belt  310  to the blood pump  92 , also previously described. The third motor  306  is mechanically linked by a drive belt  312  to the ultrafiltration pump  144 , also as previously described. 
     A drive belt  314  also mechanically links the first motor to the first, second, third, and fourth clamping elements  244 ,  246 ,  248 , and  250 , via a cam actuator mechanism  316 . The cam actuator mechanism  316  includes, for each clamping element  244 ,  246 ,  248 , and  250  a pinch valve  318  mechanically coupled to a cam  320 . The cams  320  rotate about a drive shaft  322 , which is coupled to the drive belt  314 . 
     Rotation of the cams  320  advances or withdraws the pinch valves  318 , according to the surface contour machined on the periphery of the cam  320 . When advanced, the pinch valve  318  closes the overlying clamp regions of the fluid circuit bag  228  that lay in its path. When withdrawn, the pinch valve  318  opens the overlying clamp regions. 
     The cams  320  are arranged along the drive shaft  322  to achieve a predetermined sequence of pinch valve operation. During the sequence, the rotating cams  320  first simultaneously close all the clamping elements  244 ,  246 ,  248 , and  250  for a predetermined short time period, and then open clamping elements  244  and  248 , while closing clamping elements  246  and  250  for a predetermined time period. The rotating cams  320  then return all the clamping elements  244 ,  246 ,  248 , and  250  to a simultaneously closed condition for a short predetermined time period, and then open clamping elements  246  and  250 , while closing clamping elements  244  and  248  for a predetermined time period. 
     The sequence is repeated and achieves the balanced cycling of replacement fluid and waste fluid through the containers  212  and  214 , as previously described. A chamber cycle occurs in the time interval that the valve elements  244 ,  246 ,  248 , and  250  change from a simultaneously closed condition and return to the simultaneously closed condition. 
     The cam actuator mechanism  316  mechanically links the clamping elements  244 ,  246 ,  248 , and  250  ratiometrically with the first motor  302 . As the motor  302  increases or decreases the speed of the dual header waste and replacement pump  152 , the operation of the clamping elements  244 ,  246 ,  248  and  250  increases or decreases a proportional amount. 
     In a preferred embodiment, the ratio is set so that the flow rate per unit time through the waste pump header region  154  (i.e., through waste path  66 ) approximately equals three-fourths of the volume of the waste compartment  212 R/ 214 R, while maintaining the cycle rate at less than 10 cycles per minute. For example, if the chamber volume is 20 cc, the cycle occurs after 15 to 17 cc of waste fluid enters the compartment. 
     In the illustrated embodiment, the waste pump header region  154  is made smaller in diameter than the replacement fluid header region  200 . Thus, during operation of the dual header pump  152 , the flow rate through the replacement fluid header region  200  (through replacement fluid path  68 ) will always be larger than the flow rate through the waste pump header region  154  (through waste path  68 ). Due to the high flow rate through the replacement fluid path  68 , a pressure relief path  240  with pressure relief bypass valve  242  is provided, to prevent overfilling. In the illustrated embodiment, the valve  242  is a mechanically spring biased pressure regulator, and serves the pressure regulation and bypass function of the machine  16 . 
     In this arrangement, the in-line compartment that receives waste fluid will fill to approximately three-fourths of its volume during each cycle, displacing an equal amount of replacement fluid from its companion compartment. At the same time, the other in-line compartment that receives replacement fluid will fill completely. If the compartment completely fills with replacement fluid before the end of the cycle, the pressure relief bypass valve  242  will open to circulate replacement fluid through the relief path  240  to prevent overfilling. During the next cycle, waste fluid in the compartment will be completely displaced by the complete fill of replacement fluid in its companion compartment. 
     The provision of a higher flow rate in the replacement fluid path also facilitates initial priming (as will be described later). Only several chamber cycles are required to completely prime the in-line containers  212  and  214  with replacement fluid before fluid balancing operations begin. 
     The pump and valve system  300  used in association with the layered fluid circuit bag  228  achieves accurate fluid balancing during frequent hemofiltration. Due to the smaller volumes of replacement fluid required during each frequent hemofiltration session, slight variations that may occur (e.g., plus or minus 5%) between fluid volume removed and fluid volume replaced do not lead to large volume shifts. As a result of accurate balancing of small fluid volumes, a person undergoing frequent hemofiltration does not experience significant day-to-day swings in body fluid volume, and more precise control of the person&#39;s body fluid and weight can be achieved. 
     C. Supplying Ancillary Materials 
     The system  10  further includes a source  252  or sources that supply ancillary materials  20  to the treatment location  12  for use in association with the cartridge  18  and machine  16 . The ancillary materials  20  include the replacement fluid containers  176 , as prescribed by the person&#39;s physician. 
     The ancillary materials  20  may also include an anticoagulant prescribed by a physician. However, anticoagulant may not be required for every person undergoing frequent hemofiltration, depending upon treatment time, treatment frequency, blood hematocrit, and other physiologic conditions of the person. 
     The ancillary materials  20  can also include the hemofilter  34 , although, alternatively, the tray  48  can carry the hemofilter  34 , or the hemofilter  34  can comprise an integrated component of the cartridge  18 . 
     Through operation of the machine  16 , cartridge  18 , and ancillary materials  20  supplied by the system  10 , the person&#39;s blood is conveyed through the hemofilter  34  for removal of waste fluid containing urea and other toxins. Replacement fluid is exchanged for the removed waste fluid, to maintain the person&#39;s electrolyte balance and acid/base balance. The replacement fluid is also balanced against an additional waste fluid removal, to yield a net ultrafiltration loss, as prescribed by the person&#39;s physician. 
     The composition of an optimal replacement fluid solution usable during frequent hemofiltration consist of a balanced salt solution containing the major cationic and anionic plasma constituents, including bicarbonate or another anion from which net bicarbonate can be generated by metabolism. Specific cationic substances removed by frequent hemofiltration that require replacement typically include sodium, potassium and calcium. Specific anionic substances removed by frequent hemofiltration that require replacement include chloride and either bicarbonate or another anion that can be metabolized into bicarbonate, such as acetate, citrate, or, typically, lactate. 
     The replacement fluid for frequent hemofiltration should exclude phosphorus and other anionic substances. These materials typically accumulate in undesirable amounts in persons experiencing renal failure and are either difficult to remove in large amounts during hemofiltration or are safely removed without need for specific replacement. 
     The concentration of sodium in a replacement fluid for frequent hemofiltration should fall slightly below that of the typical blood filtrate concentration of 135 to 152 meq/liter. The optimal range for sodium in the replacement fluid for frequent hemofiltration is 128-132 meq/liter, and typically 130 meq/liter. This concentration allows for a net sodium removal during frequent hemofiltration sessions, which is easily tolerated due to the smaller replacement fluid volumes necessary for frequent hemofiltration. This concentration also results in a minimal net drop in serum osmolality, so as to decrease extracellular volume to a extent sufficient to maintain euvolemia while ameliorating thirst in the person undergoing frequent hemofiltration. 
     The metabolism of calcium is quite complicated and much less straightforward than sodium. Thus, the optimal concentration in a replacement fluid for frequent hemofiltration should be much closer to the normal physiologic range of calcium in plasma, i.e., in a range of 2.5 to 3.5 meq/liter, and typically 2.7 meq/liter. This calcium concentration range is required to prevent tetany, which can result from excessive removal of ionized calcium, while removing excessive serum calcium that may result from the oral calcium supplements and phosphorus binders frequently used by persons requiring hemofiltration. 
     Selecting an optimal concentration of potassium in a replacement fluid for frequent hemofiltration is important. Typically, the potassium concentrations selected for replacement fluids used during infrequent hemofiltration (3 times a week or less) or during hemodialysis are quite low, e.g., in the range of 0 to 3 meq/liter. These low concentrations of potassium are required for infrequent hemofiltration therapies, to prevent life threatening accumulations of serum potassium between treatment sessions. Interim accumulation of toxic levels of potassium can be encountered between infrequent hemofiltration sessions, both because of decreased renal excretion of potassium and the interim development of acidosis between sessions. This, in turn, can result in total body potassium depletion in many persons undergoing infrequent therapy. Potassium depletion results in vasoconstriction and subsequent alterations in regional blood flow. Potassium depletion also interferes with the efficiency of solute removal, as measured by a decrease in Kt/V for urea, which is a dimensionless parameter commonly employed to measure the adequacy of dialysis. Potassium depletion is also implicated in the pathogenesis of hypertension in patients undergoing hemodialysis or infrequent hemofiltration. 
     In contrast, the optimal range for potassium in a replacement fluid used for frequent hemofiltration can fall in a higher range than that required of less frequent treatment schedules, laying in the range of 2.7 to 4.5 meq/liter, and typically 4.0 meq/liter. This higher concentration of potassium, when infused frequently in smaller fluid replacement volumes, prevents potassium depletion, while also maintaining more stable potassium levels to prevent toxic accumulation of potassium between sessions. 
     Additional benefits derived from frequent hemofiltration in the control of serum potassium lay in the more physiologic control of acidosis, which prevents extra cellular shift of potassium from the intracellular space. In addition to the control of acidosis, the avoidance of total body potassium depletion enhances aldosterone-mediated gut elimination of potassium, further safeguarding against hyperkalemia. 
     The optimal range for chloride concentrations in a replacement fluid used for frequent hemofiltration is 105 to 115 meq/liter, and typically 109 meq/liter. This concentration most closely approximates the normal sodium to chloride ratio of 1.38:1 maintained in the plasma. The small deviation from this ratio in the replacement fluid itself allows for the normalization of the ratio by daily oral intake of these electrolytes. Due to the larger replacement fluid volumes needed for infrequent treatment (three times per week or less), this deviation from the normal 1.38:1 ratio are exaggerated, and can lead to a hyperchloremic acidosis. Due to the use of smaller fluid volumes during each frequent hemofiltration session, hyperchloremic acidosis can be avoided. 
     The optimal range of bicarbonate or an equivalent in a replacement fluid used for frequent hemofiltration is also important. Concentrations must adequately replace filtered bicarbonate while controlling acidosis and avoiding metabolic alkalosis. Because of precipitation of calcium carbonate in solutions containing dissolved calcium and bicarbonate, bicarbonate itself is generally impractical for use in a replacement fluid. Other substances such as acetate, citrate, or typically lactate, are substituted. These substances are metabolized by the body into bicarbonate and do not precipitate when placed into solution with the cationic substances mentioned previously. 
     The range of lactate necessary to replace filtered bicarbonate and control acidosis without alkalemia is 25 to 35 mmoles per liter, and typically 28 mmoles per liter. Due to the large volumes of replacement fluid used for infrequent therapies, use of lactate containing replacement fluids can result in lactate accumulation and pathologic alterations in the lactate:pyruvate ratio and resulting in undesirable changes in cellular redox potentials. However, these effects are minimized by the frequent use of smaller volumes of replacement fluid during frequent hemofiltration. This also results in more physiologic control of acidosis and, secondarily, serum potassium concentration. The latter is accounted for by reduced extra-cellular shift of potassium caused by acidosis. 
     The above observation also holds true for acetate and citrate, as well. The typical range of acetate in replacement fluid would be 25 to 35 mmoles/liter, and typically 30 mmoles/liter. The typical range of citrate would be 16 to 24 mmoles/liter, and typically 20 mmoles/liter. These concentrations render solutions containing acetate impractical for large volume replacements on an infrequent basis, because of toxicity incurred by the accumulation of acetate. These include both cardiac and hepatic toxicity. There are additional issues of calcium and magnesium chelation, which become significant when citrate is used in the large volumes necessary for infrequent therapy. These toxic effects attributable to acetate or citrate are minimized by the smaller replacement volumes required for daily hemofiltration. 
     The unique combination of electrolytes and basic substances discussed above represent a novel solution to the problem of choosing replacement fluid for frequent hemofiltration. The same constituents would not likely be applicable to less frequent treatment schedules. 
     Frequent hemofiltration minimizes the depletion of blood electrolytes during each hemofiltration session. Thus, the replacement fluid need not include replacement electrolytes. The source  252  may therefore supply relatively inexpensive commodity solutions of physiologic fluids, free of electrolytes, e.g., normal saline or Ringer&#39;s lactate (which typically contains 6 mg/ml sodium chloride (130 meq/liter); 3.1 mg/ml of sodium lactate (28 meq/liter); 0.3 mg/ml potassium chloride (4 meq/liter); 0.2 mg/ml calcium chloride (2.7 meq/liter, 109 meq/liter at an osmolarity of 272 mos/liter); at a pH of 6.0 to 7.5). When buffered with citrate, Ringer&#39;s lactate effectively achieves the fluid balancing function. The citrate used to buffer the inexpensive, electrolyte-free replacement fluid can also serve the additional function of anticoagulating the blood as it undergoes hemofiltration in the first place. 
     The source  252  supplying the ancillary materials  20  can comprise one or more companies or businesses that manufacture the ancillary materials or that otherwise distributes the ancillary materials  20  to the treatment location  12 . 
     D. Exemplary Frequent Hemofiltration Modalities 
     The system  10  serves to enable frequent hemofiltration with high blood flow rates. The high blood flow rates reduce the processing time, and also significantly increases the transport rate of uremic toxins across the hemofiltration membrane. The frequent hemofiltration that the system  10  enables removes high concentrations of uremic toxins, without requiring the removal of high fluid volumes, with the attendant loss of electrolytes. The system  10  thereby provides multiple benefits for the individual, i.e., a tolerable procedure time (e.g., about one to two hours), with high clearance of uremic toxins, without high depletion of liquids and physiologic electrolyte levels in the blood, accurate fluid volume balancing, and use of inexpensive commodity replacement fluids. 
     The machine  16  and cartridge  18  that the system  10  may provide can be used to provide diverse frequent hemofiltration modalities on a continuous or extended basis, e.g., normal frequent hemofiltration, balanced frequent hemofiltration, only net ultrafiltration, and replacement fluid bolus. 
     During normal frequent hemofiltration, blood is drawn from the person at a prescribed flow rate (BFR). Waste fluid is removed from the arterial blood flow and volumetrically balanced with replacement fluid, which is returned in the venous blood flow at a prescribed rate (RFR). A prescribed net ultrafiltration volume of waste fluid is also removed at a prescribed flow rate (UFR) with fluid balancing, to control net weight loss. Operation of the machine  16  in the normal frequent hemofiltration mode terminates when either (i) the replacement fluid sensor indicates the absence of replacement fluid flow by sensing the presence of air (i.e., no more replacement fluid) and the net ultrafiltration goal has been achieved; or (ii) the time prescribed for the session has elapsed. 
     During balanced frequent hemofiltration, normal hemofiltration occurs without an ultrafiltration function. This mode can be used for persons that experience no weight gains between treatment sessions. This mode can also be used at the end of a normal frequent hemofiltration session, when the net ultrafiltration goal was achieved before exhausting the supply of replacement fluid. 
     During only net ultrafiltration, only a net ultrafiltration volume of waste is removed from the person. No fluid is replaced. This mode can be used when it is desired only to remove fluid. This mode can also be used at the end of a normal frequent hemofiltration session, when the net ultrafiltration goal has not been achieved but the supply of replacement fluid has been exhausted. 
     During replacement fluid bolus, there is no fluid balancing and ultrafiltration functions. Blood is circulated in an extracorpeal path and a bolus of replacement fluid is added. In the illustrated embodiment, the ultrafiltration pump  144  is run in reverse at a speed lower than the waste and replacement pump  152 . This recirculates waste fluid through the waste compartments  212 R and  214 R, to add replacement fluid from the replacement compartments  212 F and  214 F to the patient. The waste fluid that is recirculated limits waste fluid removal through the hemofilter  34 , yielding replacement fluid addition without additional waste fluid removal. The net volume of added replacement fluid conveyed to the patient equals the volume of waste fluid recirculated. This mode can be used to return fluid to a person in a bolus volume, e.g., during a hypotensive episode or during rinse back at the end of a given hemofiltration session. 
     1. Controlling the Blood Flow Rate 
     High blood flow rates (e.g., at least 300 ml/min, and preferably at least 600 ml/min) are conducive to rapid, efficient frequent hemofiltration. The high blood flow rates not only reduce the processing time, but also significantly increases the transport rate of uremic toxins across the hemofiltration membrane. In this way, the system  10  removes high concentrations of uremic toxins, without requiring the removal of high fluid volumes, with the attendant loss of electrolytes. 
     The BFR can be prescribed by an attending physician and input by the operator at the beginning of a treatment session. Alternatively, the machine  16  can automatically control to achieve an optimal BFR and minimize procedure time, based upon a desired filtration fraction value (FF), FPR, and UFR, as follows: BFR=(RFR+UFR)/FF. 
     where: 
     FF is the desired percentage of fluid to be removed from the blood stream through the hemofilter  34 . 
     A desired FF (typically 20% to 35%) can be either preset or prescribed by the attending physician. A desired FF takes into account the desired therapeutic objectives of toxin removal, as well as the performance characteristics of the hemofilter  34 . A nominal FF can be determined based upon empirical and observed information drawn from a population of individuals undergoing hemofiltration. A maximum value of 30% is believed to be appropriate for most individuals and hemofilters  34 , to achieve a desired therapeutic result without clogging of the hemofilter  34 . 
     In the illustrated embodiment, air leaks into the extracorporeal circuit (due, e.g., to improper patient line connection) is monitored by the sensor  98 . The sensor  98  is an ultrasonic detector, which also can provide the added capacity to sense flow rate. 
     In the illustrated embodiment, the machine  16  senses waste fluid pressure to control the blood flow rate to optimize the removal of fluid across the hemofilter  34 . As arterial blood flows through the hemofilter  34  (controlled by the blood pump  92 ), a certain volume of waste fluid will cross the membrane into the waste line  118 . The volume of waste fluid entering the waste line  118  depends upon the magnitude of the waste fluid pressure, which is sensed by the sensor  132 . The waste fluid pressure is adjusted by controlling the waste fluid removal rate through the fluid balancing compartments (i.e., through control of the waste and replacement pump  152 ). 
     The machine  16  monitors the waste fluid pressure at sensor  132 . By keeping the pressure sensed by the sensor  132  slightly above zero, the machine  16  achieves the maximum removal of fluid from the blood at then operative arterial flow rate. Waste pressure values significantly higher than zero will limit removal of fluid from the blood and keep a higher percentage of waste fluid in the blood (i.e., result in a lower filtration fraction). However, this may be desirable for persons who tend to clot easier. 
     By sensing waste fluid pressure by sensor  132 , the machine  16  also indirectly monitors arterial blood pressure. At a constant blood pump speed, changes in arterial blood flow caused, e.g., by access clotting or increased arterial blood pressure, makes less waste fluid available in the waste line  118 . At a given speed for pump  152 , change in arterial blood flow will lower the sensed waste pressure at sensor  132  to a negative value, as fluid is now drawn across the membrane. The machine  16  adjusts for the change in arterial blood flow by correcting the waste fluid removal rate through the pump  152 , to bring the waste pressure back to slightly above zero, or to another set value. 
     In this arrangement, a pressure sensor in the arterial blood line is not required. If the arterial pressure increases at a fixed blood pump speed, the blood flow must drop, which will result in a sensed related drop in the waste fluid pressure by the sensor  132 . Adjusting the pump  152  to achieve a pressure slightly above zero corrects the reduced arterial blood flow. In this arrangement, since the waste fluid pressure is maintained at a slightly positive value, it is not possible to develop a reverse transmembrane pressure, which conveys waste fluid back to the person&#39;s blood. The maximum transmembrane pressure is the maximum venous pressure, since waste fluid pressure is held slightly positive. 
     In an alternative arrangement, arterial blood pressure can be measured by a sensor located upstream of the blood pump. The rate of the blood pump is set to maintain sensed arterial blood pressure at a predetermined control point. This controls the blood pump speed to a maximum rate. The control point can be determined by the attending physician, e.g., on a day-to-day basis, to take into account the blood access function of the person undergoing treatment. Use of an arterial pressure control point minimizes the treatment time, or, alternatively, if treatment time is fixed, the removal of waste fluid can maximized. 
     In this arrangement, safety alarms can be included should the sensed arterial pressure become more negative than the control point, along with a function to shut down the blood pump should an alarm occur. 
     2. Controlling the Replacement Fluid Flow Rate 
     RFR can be prescribed by an attending physician and inputted by the operator at the beginning of a treatment session. 
     Alternatively, the machine  16  can automatically control RFR to minimize procedure time based upon the desired filtration fraction value (FF), BFR, and UFR, as follows: RFR=(BFR*FF)−UFR. 
     In the illustrated embodiment, waste is conveyed to the waste side compartments  212 R and  214 R, and replacement fluid is conveyed to the replacement side compartments  212 F and  214 F, by operation of the dual header waste and replacement fluid pump  152 . Alternatively, separate waste and replacement fluid pumps can be provided. 
     The speed of the waste and replacement pump  152  is controlled to achieve the desired RFR. The machine  16  cycles the inlet and outlet valve assemblies  216 ,  218 , as described. The machine  16  cycles between the valve states according to the speed of the waste and fluid pump  152  to avoid overfilling the compartments  212 ,  214  receiving fluid. Various synchronization techniques can be used. 
     In one arrangement, as previously described, the interval of a valve cycle is timed according to the RFR, so that the volume of waste or replacement fluid supplied to waste compartment during the valve cycle interval is less than volume of the compartment receiving the waste fluid. overfilling is thereby avoided without active end of cycle monitoring. In a preferred embodiment, the waste fluid is pumped at RFR, and the replacement fluid is pumped at a higher rate, but is subject to pressure relief through the pressure relief path  240  upon filling the corresponding replacement side compartment  214 . 
     In another arrangement, the timing of the transition between valve cycles is determined by active sensing of pressure within the compartments  212 ,  214  receiving liquid. As the interior wall  210  reaches the end of its travel, pressure will increase, signaling an end of cycle to switch valve states. 
     In yet another arrangement, the location of the interior wall  210  as it reaches the end of its travel is actively sensed by end of cycle sensors on the machine  16 . The sensors can comprise, e.g., optical sensors, capacitance sensors, magnetic Hall effect sensors, or by radio frequency (e.g., microwave) sensors. The termination of movement of the interior wall  210  indicates the complete filling of a compartment and the concomitant emptying of the other compartment, marking the end of a cycle. The sensors trigger an end of cycle signal to switch valve states. 
     The machine  16  counts the valve cycles. Since a known volume of replacement fluid is expelled from a replacement side compartment during each valve cycle, the machine  16  can derive the total replacement volume from the number of valve cycles. The replacement fluid volume is also known by the number of replacement fluid bags of known volume that are emptied during a given session. 
     Frequent hemofiltration can be conducted without fluid replacement, i.e., only net ultrafiltration, by setting RFR to zero. 
     3. Controlling the Ultrafiltration Flow Rate 
     UFR can be prescribed by an attending physician and inputted by the operator at the beginning of a treatment session. 
     The speed of the ultrafiltration pump is monitored and varied to maintain UFR. 
     Frequent hemofiltration can be conducted without an ultrafiltration function, i.e., balanced hemofiltration, by setting UFR to zero. 
     4. Active Filtration Rate Control 
     In an alternative embodiment, the machine  16  also actively controls the filtration rate along with the blood flow rate, to achieve a desired magnitude of uremic toxin removal through the hemofilter  34 . 
     In this embodiment, the machine  16  includes a flow restrictor which is positioned to engage a region of the venous blood return path in the circuit  56 . The restrictor comprises, e.g., a stepper-driven pressure clamp, which variably pinches a region of the venous blood return path upon command to alter the outlet flow rate of blood. This, in turn, increases or decreases the transmembrane pressure across the filter membrane. 
     For a given blood flow rate, waste transport across the filter membrane will increase with increasing transmembrane pressure, and vice versa. However, at some point, an increase in transmembrane pressure, aimed at maximizing waste transport across the filter membrane, will drive cellular blood components against the filter membrane. Contact with cellular blood components can also clog the filter membrane pores, which decreases waste transport through the membrane. 
     Filtration rate control can also rely upon an upstream sensor mounted on the machine  16 . The sensor is positioned for association with a region of the arterial blood supply path between the blood pump  92  and the inlet of the hemofilter  34 . The sensor senses the hematocrit of the blood prior to its passage through the filter membrane which will be called the “pre-treatment hematocrit”). In the arrangement, a downstream sensor is also mounted on the machine  16 . The sensor is positioned for associated with a region of the venous blood return path downstream of the outlet of the hemofilter  34 . The sensor senses the hematocrit of the blood after its passage through the hemofilter  34 (which will be called the “post-treatment hematocrit”). 
     The difference between pre-treatment and post-treatment hematocrit is a function of the degree of waste fluid removal by the hemofilter  34 . That is, for a given blood flow rate, the more waste fluid that is removed by the hemofilter  34 , the greater the difference will be between the pre-treatment and post-treatment hematocrits, and vice versa. The machine  16  can therefore derive an actual blood fluid reduction ratio based upon the difference detected by sensors between the pre-treatment and post-treatment hematocrits. The machine  16  periodically compares the derived fluid reduction value, based upon hematocrit sensing by the sensors, with the desired FF. The machine  16  issues a command to the flow restrictor to bring the difference to zero. 
     5. Set Up Pressure Testing/Priming 
     Upon mounting the disposable fluid circuit on the machine  16 , the pumps can be operated in forward and reverse modes and the valves operated accordingly to establish predetermined pressure conditions within the circuit. The sensors monitor build up of pressure within the circuit, as well as decay in pressure over time. In this way, the machine can verify the function and integrity of pumps, the pressure sensors, the valves, and the flow paths overall. 
     The machine  16  can also verify the accuracy of the ultrafiltration pump using the fluid balancing containers. 
     Priming can be accomplished at the outset of each frequent hemofiltration session to flush air and any residual fluid from the disposable fluid circuit. Fluid paths from the arterial access to the waste bag are flushed with replacement fluid. Replacement fluid is also circulated through the fluid balancing containers into the waste bag and the venous return path. The higher flow rate in the replacement fluid path and timing of the fluid balancing valve elements assure that the replacement fluid compartments completely fill and the waste fluid compartments completely empty during each cycle for priming. 
     6. Rinse Back 
     As previously described, waste fluid pressure is controlled and monitored to assure its value is always positive. Likewise, pressure between the blood pump and the hemofilter must also be positive, so that air does not enter this region of the circuit. Forward operation of the blood pump to convey arterial blood into the hemofilter establishes this positive pressure condition. 
     The rinse back of blood at the end of a given frequent hemofiltration procedure can also be accomplished without risk of air entry into the blood flow path. Rinse can be accomplished by stopping the blood pump and operating the ultrafiltration pump in the reverse bolus mode, as already described. The recirculation of waste fluid by the ultrafiltration pump through the fluid balancing compartments introduces replacement fluid to flush the venous return line. When complete, the venous clamp is closed. 
     With the venous clamp closed, continued operation of the ultrafiltration pump in the reverse bolus mode introduces replacement fluid from the fluid balancing compartments into the hemofilter, in a back flow direction through the outlet port. The blood pump is run in reverse to convey the replacement fluid through the hemofilter and into the arterial blood line. Residual blood is flushed from the blood line. The blood pump is operated in reverse at a rate slower than the reverse bolus rate of the ultrafiltration pump (which supplies replacement fluid to the outlet port of the hemofilter), so that air cannot enter the blood path between the blood pump and the hemofilter. At this stage of the rinse back, the arterial blood line is also subject to positive pressure between the blood pump and the arterial access, so no air can enter this region, either. 
     In this arrangement, no air sensing is required in the arterial blood line and a pressure sensor between the blood pump and the hemofilter is required. 
     E. Supplying Telemetry 
     The system  10  also preferably includes a telemetry network  22  (see  FIGS. 1 and 19 ). The telemetry network  22  provides the means to link the machine  16  at the treatment location  12  in communication with one or more remote locations  254  via, e.g., cellular networks, digital networks, modem, Internet, or satellites. A given remote location  254  can, for example, receive data from the machine  16  at the treatment location  12  or transmit data to a data transmission/receiving device  296  at the treatment location  12 , or both. A main server  256  can monitor operation of the machine  16  or therapeutic parameters of the person undergoing frequent hemofiltration. The main server  256  can also provide helpful information to the person undergoing frequent hemofiltration. The telemetry network  22  can download processing or service commands to the data receiver/transmitter  296  at the treatment location  12 . 
     Further details about the telemetry aspect of the system  10  will now be described. 
     1. Remote Information Management 
       FIG. 19  shows the telemetry network  22  in association with a machine  16  that carries out frequent hemofiltration. The telemetry network  22  includes the data receiver/transmitter  296  coupled to the machine  16 . The data receiver/transmitter  296  can be electrically isolated from the machine  16 , if desired. The telemetry network  22  also includes a main data base server  256  coupled to the data receiver/transmitter  296  and an array of satellite servers  260  linked to the main data base server  256 . 
     The data generated by the machine  16  during operation is processed by the data receiver/transmitter  296 . The data is stored, organized, and formatted for transmission to the main data base server  256 . The data base server  256  further processes and dispenses the information to the satellite data base servers  260 , following by pre-programmed rules, defined by job function or use of the information. Data processing to suit the particular needs of the telemetry network  22  can be developed and modified without changing the machine  16 . 
     The main data base server  256  can be located, e.g., at the company that creates or manages the system  10 . The satellite data base servers  260  can be located, for example, at the residence of a designated remote care giver for the person, or at a full time remote centralized monitoring facility staffed by medically trained personnel, or at a remote service provider for the machine  16 , or at a company that supplies the machine  16 , or the processing cartridge  18 , or the ancillary processing material to the treatment location  12 . 
     Linked to the telemetry network  22 , the machine  16  acts as a satellite. The machine  16  performs specified therapy tasks while monitoring basic safety functions and providing the person at the treatment location  12  notice of safety alarm conditions for resolution. Otherwise, the machine  16  transmits procedure data to the telemetry network  22 . The telemetry network  22  relieves the machine  16  from major data processing tasks and related complexity. It is the main data base server  256 , remote from the machine  16 , that controls the processing and distribution of the data among the telemetry network  22 , including the flow of information and data to the person undergoing therapy. The person at the treatment location  12  can access data from the machine  16  through the local date receiver/transmitter  296 , which can comprise a laptop computer, handheld PC device, web tablet, or cell phone. 
     The machine  16  can transmit data to the receiver/transmitter  296  in various ways, e.g., electrically, by phone lines, optical cable connection, infrared light, or radio frequency, using cordless phone/modem, cellular phone/modem, or cellular satellite phone/modem. The telemetry network  22  may comprise a local, stand-alone network, or be part of the Internet. 
     For example, when the machine  16  notifies the person at the treatment location  12  of a safety alarm condition, the safety alarm and its underlying data will also be sent to the main server  256  on the telemetry network  22  via the receiver/transmitter  296 . While the person undergoing therapy or the care giver works to resolve the alarm condition, the main server  256  determines, based upon the prevailing data rule, whether the alarm condition is to be forwarded to other servers  260  in the network  22 . 
     When an alarm condition is received by the main server  256 , the main server  256  can locate and download to the receiving device  296  the portion of the operator&#39;s manual for the machine that pertains to the alarm condition. Based upon this information, and exercising judgment, the operator/user can intervene with operation of the machine  16 . In this way, the main server  256  can provide an automatic, context-sensitive help function to the treatment location  12 . The telemetry network  22  obviates the need to provide on-board context-sensitive help programs for each machine  16 . The telemetry network  22  centralizes this help function at a single location, i.e., a main server  256  coupled to all machines  16 . 
     The telemetry network  22  can relay to an inventory server  262  supply and usage information of components used for frequent hemofiltration at each treatment location  12 . The server  262  can maintain treatment site-specific inventories of such items, such as cartridges  18 , replacement fluid, and hemofilters  34 . The company or companies of the system  10  that supply the machine  16 , or the processing cartridge  18 , or the ancillary processing material to the treatment location  12  can all be readily linked through the telemetry network  22  to the inventory server  262 . The inventory server  262  thereby centralizes inventory control and planning for the entire system  10 , based upon information received in real time from each machine  16  at each treatment location  12 . 
     The telemetry network  22  can relay to a service server  264  hardware status information for each machine  16  at every treatment location  12 . The service server  264  can process the information according to preprogrammed rules, to generate diagnostic reports, service requests or maintenance schedules. The company or companies of the system  10  that supply or service the machine  16  can all be readily linked through the telemetry network  22  to the service server  264 . The service server  264  thereby centralizes service, diagnostic, and maintenance functions for the entire system  10 . Service-related information can also be sent to the treatment location  12  via the receiving device  296 . 
     The telemetry network  22  can also relay to a treatment monitoring server  266 , treatment-specific information pertaining to the hemofiltration therapy provided by each machine  16  for the person at each treatment location  12 . Remote monitoring facilities  268 , staffed by medically trained personnel, can be readily linked through the telemetry network  22  to the treatment monitoring server  266 . The monitoring server  266  thereby centralizes treatment monitoring functions for all treatment locations  12  served by the system  10 . Treatment-monitoring information can also be sent to the treatment location  12  via the receiving device  296 . 
     The telemetry network  22  can also provide through the device  296  an access portal for the person undergoing frequent hemofiltration to the myriad services and information contained on the Internet, e.g., over the web radio and TV, video, telephone, games, financial management, tax services, grocery ordering, prescriptions purchases, etc. The main server  256  can compile diagnostic, therapeutic, and/or medical information to create a profile for each person served by the system  10  to develop customized content for that person. The main server  256  thus provide customized ancillary services such as on line training, billing, coaching, mentoring, and provide a virtual community whereby persons using the system  10  can contact and communicate via the telemetry network  22 . 
     The telemetry network  22  thus provides the unique ability to remotely monitor equipment status, via the internet, then provide information to the user, also via the internet, at the location of the equipment. This information can includes, e.g., what page on the operator&#39;s manual would be the most helpful for their current operational situation, actual data about the equipment&#39;s performance (e.g., could it use service, or is it set up based on the caretaker&#39;s recommendations, data about the current session i.e., buttons pressed, alarms, internal machine parameters, commands, measurements. 
     The remote site can monitor the equipment for the same reasons that the user might. It can also retrieve information about the machine when it is turned off because the telemetry device is self-powered. It retains all information about the machine over a period of time (much like a flight recorder for an airplane). 
     2. On Site Programming 
     (i) Using the Telemetry Network 
     The main server  256  on the telemetry network  22  can also store and download to each machine  16  (via the device  296 ) the system control logic and programs necessary to perform a desired frequent hemofiltration procedure. Programming to alter a treatment protocol to suit the particular needs of a single person at a treatments site can be developed and modified without a service call to change the machine  16  at any treatment location  12 , as is the current practice. System wide modifications and revisions to control logic and programs that condition a machine  16  to perform frequent hemofiltration can be developed and implemented without the need to retrofit each machine  16  at all treatment locations  12  by a service call. This approach separates the imparting of control functions that are tailored to particular procedures, which can be downloaded to the machine  16  at time of use, from imparting safety functions that are generic to all procedures, which can be integrated in the machine  16 . 
     (ii) Using the Cartridge 
     Alternatively, the control logic and programs necessary to perform a desired frequent hemofiltration procedure can be carried in a machine readable format on the cartridge  18 . Scanners on the machine  16  automatically transfer the control logic and programs to the machine  16  in the act of loading the cartridge  18  on the machine  16 . Bar code can be used for this purpose. Touch contact or radio frequency silicon memory devices can also be used. The machine  16  can also include local memory, e.g., flash memory, to download and retain the code. 
     For example, as  FIG. 2  shows, the machine  16  can include one or more code readers  270  on the chassis panel  26 . The tray  48  carries, e.g., on a label or labels, a machine readable (e.g., digital) code  272  (see  FIG. 10 ) that contains the control logic and programs necessary to perform a desired frequent hemofiltration procedure using the cartridge  18 . Loading the tray  48  on the machine  16  orients the code  272  to be scanned by the reader(s)  270 . Scanning the code  272  downloads the control logic and programs to memory. The machine  16  is thereby programmed on site. 
     The code  272  can also include the control logic and programs necessary to monitor use of the cartridge  18 . For example, the code  272  can provide unique identification for each cartridge  18 . The machine  16  registers the unique identification at the time it scans the code  272 . The machine  16  transmits this cartridge  18  identification information to the main server  256  of the telemetry network  22 . The telemetry network  22  is able to uniquely track cartridge  18  use by the identification code throughout the system  10 . 
     Furthermore, the main server  256  can include preprogrammed rules that prohibit multiple use of a cartridge  18 , or that limit extended uses to a prescribed period of time. An attempted extended use of the same cartridge  18  on any machine  16 , or an attempted use beyond the prescribed time period, will be detected by the machine  16  or the main server  256 . In this arrangement, the machine  16  is disabled until an unused cartridge  18  is loaded on the machine  16 . 
     Service cartridges can also be provided for the machine  16 . A service cartridge carries a code that, when scanned by the reader or readers on the chassis panel  26  and downloaded to memory, programs the machine  16  to conduct a prescribed service and diagnostic protocol using the service cartridge  18 . 
     (iii) Using an Overlay 
     Alternatively, or in combination with any of the foregoing on-site machine  16  programming techniques, the chassis panel  26  can be configured to receive overlays  274 ,  276 ,  278 ,  280  (see  FIG. 20 ), which are specific to particular hemofiltration modalities or therapies that the machine  16  can carry out. For example, in the context of the illustrated embodiment, one overlay  274  would be specific to the normal frequent hemofiltration mode, a second overlay  276  would be specific to the balanced frequent hemofiltration mode, a third overlay  278  would be specific to the only net ultrafiltration mode, and a fourth overlay  280  would be specific to the replacement fluid bolus mode. Other overlays could be provided, e.g., for a pediatric hemofiltration procedure, or a neo-natal hemofiltration procedure. 
     When a treatment location  12  wants to conduct a particular hemofiltration modality, the treatment location  12  mounts the associated overlay on the chassis panel  26 . Each overlay contains a code  282  or a chip imbedded in the overlay that is scanned or discerned by one or more readers  284  on the chassis panel  26  after the overlay is mounted on the chassis panel  26 . The code  282  is downloaded to flash memory on the machine  16  and programs the machine  16  to conduct hemofiltration in that particular mode. 
     A person at the treatment location  12  mounts the appropriate overlay  274 ,  276 ,  278 ,  280  and then mounts a cartridge  18  on the chassis panel  26 . The machine  16  is then conditioned by the overlay and made capable by the cartridge  18  to conduct that particular mode of hemofiltration using the cartridge  18 . In this way, a universal cartridge  18 , capable of performing several hemofiltration modes, can be provided. It is the overlay that conditions the machine  16  to perform different treatment modalities. Alternatively, the operator can link the overlay, machine, and cartridge together by therapy type. 
     Furthermore, treatment-site specific alterations of generic hemofiltration modes can be developed and implemented. In this arrangement, treatment-site specific overlays  286  are provided for the machine  16 . The treatment site-specific overlay  286  carries a code  282  or a chip imbedded in the overlay that, when downloaded by the machine  16 , implements a particular variation of the hemofiltration mode for the person at that treatment location  12 , as developed, e.g., by an attending physician. A person at the treatment location  12  mounts the treatment-site specific overlay  286  and then mounts a universal cartridge  18  on the chassis panel  26 . The machine  16  is conditioned by the treatment site-specific overlay  286  and made capable by the universal cartridge  18  to conduct that particular specific mode of hemofiltration using the cartridge  18 . 
     An additional overlay  288  can be provided that contains code  282  or a chip imbedded in the overlay that, when scanned by the reader(s)  284  on the chassis panel  26  and downloaded to flash memory, programs the machine  16  to conduct a prescribed service and diagnostic protocol using the cartridge  18 , which is also mounted on the chassis panel  26 . 
     F. Extended Use of the Cartridge 
     The consolidation of all blood and fluid flow paths in a single, easily installed cartridge  18  avoids the potential of contamination, by minimizing the number of connections and disconnections needed during a hemofiltration session. By enabling a dwell or wait mode on the machine  16 , the cartridge  18  can remain mounted to the machine  16  after one hemofiltration session for an extended dwell or break period and allow reconnection and continued use by the same person in a subsequent session or in a continuation of a session following x-rays or testing. 
     The cartridge  18  can therefore provide multiple intermittent treatment sessions during a prescribed time period, without exchange of the cartridge  18  after each treatment session. The time of use confines are typically prescribed by the attending physician or technical staff for the treatment center to avoid biocontamination and can range, e.g., from 48 hours to 120 hours, and more typically 72 to 80 hours. The cartridge  18  can carry a bacteriostatic agent that can be returned to the patient (e.g., an anticoagulant, saline, ringers lactate, or alcohol) and/or be refrigerated during storage. 
     To reduce the change of biocontamination, the cartridge  18  can include one or more in-line sterilizing filters  178  (e.g., 0.2 m) in association with connectors that, in use, are attached to outside fluid sources, e.g., the replacement fluid source. As  FIG. 11  shows, the filter  178  can be pre-attached to the cartridge  18  and be coupled to a multiple connection set  290 , which itself is coupled to the prescribed number of replacement fluid bags  176 . Alternative (as  FIG. 21  shows), a separate customized filtration set  292  can be provided, which attaches to the connector  174  carried by the cartridge  18 . The filtration set  292  includes a sterilizing filter  178  to which an array of multiple connector leads  294  is integrated. 
     In the dwell mode of the machine  16 , fluid can be recirculated either continuously or intermittently through the circuit  56 . The fluid can be circulate past a region of ultraviolet light carried on the machine  16  to provide a bacteriostatic effect. Alternatively, or in combination with exposure to ultraviolet light, the fluid can carry a bacteriostatic agent, such as an anticoagulant, saline, ringers lactate, or alcohol, which can be returned to the person at the beginning of the next treatment session. The machine  16  and cartridge  18  can also be subjected to refrigeration during the dwell period. 
     In an alternative embodiment, an active disinfecting agent can be circulated through the circuit  56  during the dwell period. The disinfecting material can include a solution containing Amuchina™ material. This material can be de-activated by exposure to ultraviolet light prior to the next treatment session. Exposure to ultraviolet light causes a chemical reaction, during which Amuchina™ material breaks down and transforms into a normal saline solution, which can be returned to the person at the start of the next hemofiltration session. 
     G. The Operator Interface 
       FIG. 22  shows a representative display  324  for an operator interface  44  for the machine. The display  324  comprises a graphical user interface (GUI), which, in the illustrated embodiment, is displayed by the interface  44  on the exterior of the door  28 , as  FIG. 2  shows. The GUI can be realized, e.g., as a membrane switch panel, using an icon-based touch button membrane. The GUI can also be realized as a “C” language program implemented using the MS WINDOWS™ application and the standard WINDOWS 32 API controls, e.g., as provided by the WINDOWS™ Development Kit, along with conventional graphics software disclosed in public literature. 
     The GUI  324  presents to the operator a simplified information input and output platform, with graphical icons, push buttons, and display bars. The icons, push buttons, and display bars are preferably back-lighted in a purposeful sequence to intuitively lead the operator through set up, execution, and completion of a frequent hemofiltration session. 
     The GUI  324  includes an array of icon-based touch button controls  326 ,  328 ,  330 ,and  332 . The controls include an icon-based treatment start/select touch button  326 , an icon-based treatment stop touch button  328 , and an icon-based audio alarm mute touch button  330 . The controls also include an icon-based add fluid touch button  332  (for prime, rinse back, and bolus modes, earlier described). 
     An array of three numeric entry and display fields appear between the icon-based touch buttons. The fields comprise information display bars  334 ,  336 , and  338 , each with associated touch keys  340  to incrementally change the displayed information. In the illustrated embodiment, the top data display bar  334  numerically displays the Replacement Fluid Flow Rate (in ml/min), which is the flow rate for removing waste fluid and replacing it with an equal volume of replacement fluid. The middle data display bar  336  numerically displays the ultrafiltration flow rate (in kg/hr), which is the flow rate for removing waste fluid to control net weight loss. The bottom data display bar  338  numerically displays the Blood Pump Flow Rate (in ml/min). 
     The associated touch keys  340  point up (to increase the displayed value) or down (to decrease the displayed value), to intuitively indicate their function. The display bars  334 ,  336 , and  338  and touch keys  340  can be shaded in different colors, e.g., dark blue for the replacement flow rate, light blue for ultrafiltrational flow rate, and red for the blood flow rate. 
     An array of status indicator bars appears across the top of the screen. The left bar  342 , when lighted, displays a “safe” color (e.g., green) to indicate a safe operation condition. The middle bar  344 , when lighted, displays a “cautionary” color (e.g., yellow) to indicate a caution or warning condition and may, if desired, display a numeric or letter identifying the condition. The right bar  346 , when lighted, displays an “alarm” color (e.g., red) to indicate a safety alarm condition and may, if desired, display a numeric or letter identifying the condition. 
     Also present on the display is a processing status touch button  348 . The button  348 , when touched, changes for a period of time (e.g., 5 seconds) the values displayed in the information display bars  334 ,  336 , and  338 , to show the corresponding current real time values of the replacement fluid volume exchanged (in the top display bar  334 ), the ultrafiltrate volume (in the middle display bar  336 ), and the blood volume processed (in the bottom display bar  338 ). The status button  348 , when touched, also shows the elapsed procedure time in the left status indicator bar  342 . 
     The display also includes a cartridge status icon  350 . The icon  350 , when lighted, indicates that the cartridge  18  can be installed or removed from the machine  16 . 
     The GUI  324 , though straightforward and simplified, enables the operator to set the processing parameters for a given treatment session in different ways. 
     For example, in one input mode, the GUI  324  prompts the operator by back-lighting the replacement fluid display bar  334 , the ultrafiltration display bar  336 , and the blood flow rate display bar  338 . The operator follows the lights and enters the desired processing values using the associated touch up/down buttons  340 . The GUI back-lights the start/select touch button  326 , prompting the operator to begin the treatment. In this mode, the machine  16  controls the pumps to achieve the desired replacement fluid, ultrafiltration, and blood flow rates set by the operator. The machine terminates the procedure when all the replacement fluid is used and the net ultrafiltration goal is achieved. 
     In another input mode, the operator can specify individual processing objectives, and the machine  16  will automatically set and maintain appropriate pump values to achieve these objectives. This mode can be activated, e.g., by pressing the start/select touch button  326  while powering on the machine  16 . The GUI  324  changes the function of the display bars  334  and  336 , so that the operator can select and change processing parameters. In the illustrated embodiment, the processing parameters are assigned identification numbers, which can be scrolled through and selected for display in the top bar  334  using the touch up/down keys  340 . The current value for the selected parameter is displayed in the middle display bar  336 , which the operator can change using the touch up/down keys  340 . 
     In this way, the operator can, e.g., specify a desired filtration factor value (FF) along with a desired ultrafiltration flow rate (UFR) and replacement fluid flow rate (RFR). The machine will automatically control the blood pump rate (BFR), based upon the relationship BFR=(RFR+UFR)/FF, as previously described. 
     Alternatively, the operator can specify a desired filtration factor value (FF) along with a desired ultrafiltration flow rate (UFR) and blood flow rate (BFR). The machine will automatically control the replacement fluid pump rate (RFR), based upon the relationship RFR=(BFR*FF)−UFR, as already described. 
     Alternatively, the operator can specify only an ultrafiltration volume. In this arrangement, the machine  16  senses waste fluid pressure to automatically control the blood flow rate to optimize the removal of fluid across the hemofilter  34 , as previously described. Alternatively, the machine can automatically control the blood flow rate to optimize removal of fluid based a set control arterial blood pressure, as also already described. 
     As  FIG. 22  shows, the interface also preferably includes an infrared port  360  to support the telemetry function, as previously described. 
     As  FIG. 23  shows, the interface  44  can include a generic display panel  352  that receives a family of templates  354 . Each template  354  contains code  356  or chip that, when scanned or discerned by a reader  358  on the interface panel  352 , programs the look and feel of the interface  44 . In this way, a generic display panel  352  can serve to support a host of different interfaces, each optimized for a particular treatment modality. 
     Various features of the invention are set forth in the following claims.