Abstract:
This invention provides a method and apparatus for a hemodiafiltration delivery module that is used in conjunction with a UF controlled dialysis machine to enable hemodiafiltration therapy to be performed. The advantage is that one can fully utilize a current functioning dialysis machine to perform a hemodiafiltration therapy as opposed to purchasing a completely new machine that offers this capability.

Description:
CROSS REFERENCE TO RELATED APPLICATION 
     This application claims the benefit of U.S. patent application serial No. 60/267,103, filed Feb. 7, 2001, and which is hereby incorporated by reference in its entirety. 
    
    
     FIELD OF THE INVENTION 
     The invention relates to blood cleansing systems in general and, more particularly, to a blood cleansing modality commonly referred to as hemodialysis and/or hemodiafiltration. 
     BACKGROUND OF THE INVENTION 
     Hemodiafiltration combines both standard hemodialysis and hemofiltration into one process, whereby a dialyzer cartridge containing a high flux membrane is used to remove substances from the blood both by diffusion and by convection. The removal of substances by diffusion is accomplished by establishing a concentration gradient across a semipermeable membrane by flowing a dialysate solution on one side of the membrane while simultaneously flowing blood on the opposite side of the membrane. In existing systems, to enhance removal of substances using hemodiafiltration, a solution called substitution fluid is continuously added to the blood either prior to the dialyzer cartridge (pre-dilution) or after the dialyzer cartridge (post-dilution). An amount of fluid equal to that of the added substitution fluid is ultrafiltered across the dialyzer cartridge membrane carrying with it additional solutes. 
     Substitution fluid is usually purchased as a sterile/non-pyrogenic fluid (eg. 0.9% saline solution or Ringer&#39;s Lactate solution) contained in large flexible bags. The disadvantage of using this type of fluid for hemodiafiltration is the relatively high cost associated with using large volumes during treatment. As a result, methods have been developed for producing substitution fluid on-line by filtration of a non-sterile dialysate through a suitable filter cartridge rendering it sterile and non-pyrogenic. Techniques for online production of substitution fluid have been described in the literature, for example, in B. Canaud, et al., “ Hemodiafiltration Using Dialysate as Substitution Fluid”, Artificial Organs , Vol. 12, No. 2 (1987), pp. 188-190. Here, a series of filter cartridges and a substitution pump were used in conjunction with a dialysis machine as a means to generate on-line substitution fluid for the purposes of performing hemodiafiltration. What is not described, however, is how the substitution pump is operated when the blood pump stops or when the dialysis machine goes into bypass which prevents dialysate being delivered to the dialyzer and substitution pump. It is understood by those skilled in the art, that a dialysis machine may suddenly stop the blood pump or go into a dialysate bypass mode in response to a machine alarm condition (eg. due to excessive extracorporeal circuit pressure or a low or high dialysate conductivity reading). When this happens, the substitution pump should immediately be disabled or turned OFF as a means to prevent a hazardous condition from occurring (eg. creating an excessive transmembrane pressure across the dialyzer membrane). 
     Dialysis machine manufacturers have developed stand-alone dialysis machines with on-line substitution fluid suitable for hemodiafiltration. One example is the Fresenius OnLine Plus™ System, available from Fresenius Medical Care of Bad Homburg, Germany. A second example, available from Gambro AB of Lund Sweden, has been described in the literature, for example, in  D. Limido  et al., “ Clinical Evaluation of AK -100  ULTRA for Predilution HF with On - Line Prepared Bicarbonate Substitution Fluid. Comparison with HD and Acetate Postdilution HF”, International Journal of Artificial Organs , Vol. 20, No. 3 (1997), pp. 153-157. In these systems, control of the substitution fluid pump by the dialysis machine is coordinated in such a manner as to prevent unsafe or hazardous conditions. 
     In general, dialysis machines are replaced every seven years on average and cost approximately $20,000. Currently there are about 45,000 dialysis machines being used around the world, with only a very small percentage of these machines being capable of performing hemodiafiltration with online substitution fluid. Because hemodiafiltration provides a better treatment over current hemodialysis, there exists a clear need for a clinical practitioner to offer this mode of renal replacement therapy to his/her patients. As an alternative to purchasing a new hemodiafiltration machine (eg. capable of producing online substitution fluid), the present applicants have developed a diafiltration delivery module that enables online hemodiafiltration to be performed safely with an existing ultrafiltration (UF) controlled dialysis machine. 
     SUMMARY 
     This invention provides a method and apparatus for a hemodiafiltration delivery module that is used in conjunction with a UF controlled dialysis machine to enable hemodiafiltration therapy to be performed. The advantage is that one can fully utilize a current functioning dialysis machine to perform a hemodiafiltration therapy as opposed to purchasing a completely new machine that offers this capability. 
     It is an object of the present invention to overcome safety issues that arise when there is no coordination between dialysis machine events (eg. alarm conditions, mode shifts, etc.) and an externally controlled substitution fluid pump. In particular, it an object of the invention to prevent unsafe or hazardous conditions, such as can occur when the substitution pump continues to pump fluid after the blood pump on the dialysis machine stops circulating blood through the extracorporeal circuit or after the dialysis machine stops delivering dialysate fluid to the substitution pump and dialyzer. 
     In addition, it is an object of the invention to prevent blood from contaminating the final sterilizing filter (referred to as a substitution fluid filter cartridge) and thus enable the sterilizing filter to be used multiple times without having to disinfect or replace the sterilizing filter between each treatment. It is also an object of the invention to be able to provide sterile substitution fluid that can be used for priming and blood rinseback as well as providing a fluid bolus to the patient during treatment. A further object of the invention is to provide a method and apparatus that can be rinsed and disinfected either in conjunction with the dialysis machine or independently from the dialysis machine. Additional objects of the invention are to provide a means to detect when the substitution filter becomes plugged, such as by measuring the filter water permeability, and provide a means to detect the integrity of the substitution filter(s) as well as the fluid path of the diafiltration module. And finally, it is an object of the invention to fully pass the dialysate stream through at least a first filtering stage of a substitution filter, thereby improving the quality of the dialysate introduced into the dialysate compartment of the dialyzer. 
     According to an aspect of the invention, the hemodiafiltration delivery module is used in conjunction with a dialysis machine that provides ultrafiltration (UF) control as is known in the art, for example the Fresenius 2008 series dialysis machine available from Fresenius Medical Care, Lexington, Mass., or Cobe CentrySystem 3 dialysis machine available from Cobe, Lakewood, Colo. In addition, a sterilizing filter cartridge containing at least one filtration stage is used to filter the non-sterile dialysate solution and thus render it sterile and non-pyrogenic. The sterilizing filter cartridge may contain a redundant filter stage as an added measure of safety, i.e. should one of the filters fail during the diafiltration treatment. The configuration is such that fresh dialysate from the dialysis machine passes through the diafiltration delivery module prior to being delivered to the dialyzer cartridge. A portion of this dialysate fluid is drawn off from the dialysate stream by the diafiltration delivery module and is passed through the sterilizing filter (or filters) by use of a substitution pump. The sterilizing filter cartridge effectively removes bacteria that may be present in the dialysate fluid. In addition, endotoxins and other particulate material are also effectively filtered out of the dialysate to make the dialysate fluid non-pyrogenic and of suitable injectable quality. The sterile filtered dialysate fluid is then introduced into the extracorporeal circuit as a substitution fluid for diafiltration via an infusion tubing segment connecting the outlet port of the final sterilizing filter and an inlet port of the extracorporeal circuit. Due to the UF control system (which includes dialysate flow balancing components), a substantially equal volume of plasma water will be filtered across the dialyzer membrane into the dialysate compartment to make up for the “missing” volume of dialysate fluid that is drawn off by the diafiltration delivery module. As indicated above, the dialysate fluid that is not used as substitution fluid is reintroduced into the dialysate compartment of the dialyzer. Generally speaking, the process of removing and filtering a portion of dialysate fluid for use as a sterile fluid that is infused into the extracorporeal circuit as a substitution fluid is known in the art as “online hemodiafiltration”. 
     During normal operation of the invention when performing a diafiltration treatment, the diafiltration delivery module monitors at least two parameters to assure that the diafiltration process can be safely carried out. One parameter is associated with an adequate flow of dialysate through the diafiltration delivery module, such that sufficient substitution fluid can be generated. The other parameter is associated with an adequate flow of blood through the extracorporeal circuit. The latter is meant to assure that the blood does not become over hemoconcentrated as it passes through the dialyzer portion of the circuit. If this occurs, it can result in blood clotting in the dialyzer and a subsequent reduction of performance. In a first embodiment of the invention, flow meters are used to sense actual flow rates of each fluid stream (i.e. dialysate and blood flow rate). Outputs from these flow meters are used in a feedback control loop to control the substitution pump speed. In a second embodiment of the invention, a flow switch is used to detect for an adequate dialysate flow, while pressure pulses (caused by the inherent action of the peristaltic blood pump) are used as an indirect means to monitor blood flow rate. Pressure pulses are sensed either by a pressure transducer in fluid communication with one of the dialysis machine bloodline drip chamber pressure monitors or are sensed non-invasively by use of a strain gauge device that is placed in physical contact with a flexible portion of the bloodline circuit, preferably near the peristaltic blood pump. In a third embodiment, temperature sensors are used as an indirect measure of flow rate. Here, an indwelling temperature probe is placed directly in the dialysate fluid stream in the diafiltration delivery module while a surface temperature probe is placed in contact with the outside surface of the venous blood tubing line near dialyzer blood outlet. If blood flow through the extracorporeal circuit stops (eg. such as caused by a dialysis machine alarm condition), or if dialysate flow into the diafiltration delivery module becomes interrupted (eg. dialysis machine goes into a bypass mode), the extracorporeal blood and/or the dialysate fluid within the diafiltration module will begin to cool. When the rate of temperature decay exceeds a specified value, the substitution pump may be stopped to disable the diafiltration process. In a fourth embodiment, blood flow rate may be indirectly monitored using a tachometer that senses blood pump rotational speed. In a fifth embodiment, a photodiode array may be used to monitor drip chamber fluid level fluctuations (i.e. up and down motions of the fluid level within the drip chamber) caused by the peristaltic nature of the blood pump. In a sixth embodiment, dialysate flow may be indirectly monitored by inductively sensing the electrical current supplied to one of the dialysis machine solenoid valves that are associated with putting the machine in a bypass state. In addition, blood flow may be indirectly monitored by inductively sensing the electrical current supplied to the dialysis machine blood pump. In a seventh embodiment, blood flow rate may be indirectly monitored by sensing vibrations generated by the blood pump during treatment. These vibrations may be sensed mechanically using a vibration transducer that is in direct contact with a surface of dialysis machine, preferably near the blood pump, or sensed acoustically using a microphone or other sound detection device. 
     According to another aspect of the invention, the diafiltration delivery module prevents blood from backing up into the sterilizing filter. This has the advantage that the sterilizing filter can be used multiple times for subsequent treatments without having to discard and/or reprocess the sterilizing filter between treatments. In the first embodiment of the invention, this is accomplished by use of solenoid actuated pinch valve that is positioned on the flexible infusion tubing connected between the sterilizing filter and the extracorporeal filter. Control of the pinch valve is such that the valve is only opened when certain conditions are met, such as a minimum pre-filter pressure is achieved. The pinch valve may be automatically closed whenever an optical blood sensor (located between the pinch valve and the extracorporeal circuit) detects blood or when a sudden increase in pre-filter pressure is detected to be above a specified threshold value. In a seventh embodiment of the invention, a check valve is incorporated as part of the infusion tubing set as a secondary means to prevent blood from backing up into the sterilizing filter. This eliminates the need for the optical blood sensor described in the first embodiment. In an eighth embodiment of the invention, a peristaltic or roller (occluding type) pump is used in place of the pinch valve. This has the advantage of eliminating the need for the pinch valve and thus reducing the number of hardware components used in the diafiltration delivery module, however, this comes at the expense of requiring a special infusion line containing a pump segment that fits the substitution pump. 
     In a third aspect of the invention, it is desired to filter the entire dialysate stream as a means to improve the quality of dialysate entering the dialysate compartment of the dialyzer (in addition to generating sterile infusion fluid for diafiltration.) In an ninth embodiment of the invention, this is accomplished by running the substitution pump at a higher rate than the dialysate flow rate so that all the dialysate is filtered through at least a first filter stage of a sterilizing filter. A throttling valve placed in the fluid circuit on the downstream side of the first sterilizing filter is then used to generate a sufficient back pressure necessary to force the desired amount of substitution fluid through a second or final sterilizing filter. Adjustments to the aperture of the throttling valve may be based on input from a flow meter located on the dialysate stream leading to the dialyzer. As part of a tenth embodiment of the invention, it is also shown that one can control the rate of substitution fluid used for diafiltration using a feedback control loop based on flow restrictor devices and pressure inputs instead of the flow meter/throttling valve configuration. This has the distinct advantage in that one does not require use of an expensive flow meter and throttling valve to achieve this dialysate filtering aspect of the invention. 
     A fourth aspect of the invention includes being able to provide substitution fluid for other purposes besides diafiltration. For example, substitution fluid can be used for priming the extracorporeal circuit prior to treatment, for giving a fluid bolus during treatment, or for rinsing back the patient&#39;s blood at the end of treatment. In an embodiment of the invention, this may be accomplished by incorporation of an internal fluid reservoir as part of the diafiltration delivery module fluid path. Valves are appropriately included to enable one to switch flow from the incoming dialysate stream to the internal fluid reservoir as the source of substitution fluid for these purposes. This operation is necessary as the dialysis machine continuously balances fresh and spent dialysate fluid volumes as part of its UF control system. Filling of fluid reservoir is performed prior to therapy, such as part of a rinse or prime function. 
     Other aspects of the invention include a means to rinse and disinfect the diafiltration delivery module (with or without the sterilizing filter) as part of routine dialysis machine maintenance operations. Here, the diafiltration delivery module senses when there is an adequate flow of fluid (eg. rinse water) through the module as a means to assure fluid is available before turning on the substitution pump which circulates fluid through the module. Also, the dialfiltration delivery module can be configured as a standalone unit (with or without the sterilizing filter). In this mode, one can perform integrity tests on the fluid path and/or the sterilizing filter using the substitution pump to generate either positive or negative pressures in the fluid path circuit. Other tests, such as a filter plugging test, can be accomplished by recirculating fluid through the sterilizing filter at a known rate and measuring the ensuing pressure drop across the sterilizing filter. Also, by connecting an external reservoir (or reservoirs) containing a disinfecting solution and/or incorporating a heating module, disinfection of the dialfiltration module (with or without the sterilizing filter) may be accomplished in the standalone configuration. 
     And finally, in a tenth embodiment of the invention, it is further shown how the diafiltration delivery module may been separated into a treatment module and a reuse/test module. In this embodiment, the treatment module may be used without the reuse/test module when performing diafiltration treatments on the dialysis machine. In order to test the sterilizing filter and reprocess it for subsequent use, however, requires one to connect the reuse/test module to the treatment module to enable the test and disinfect functions to be performed. One advantage of this scheme is that the treatment module can be made much smaller as it contains only those components needed for carrying out the treatment aspects. This important because it is desirable to minimize the amount of space taken up by the diafiltration delivery module when connected to the dialysis machine. Another advantage has to do with preventing hazardous conditions associated with accidentally performing test/disinfect functions during treatment. For example, with separable modules, it would be impossible to invoke a hazardous disinfect process without the reuse/test module being connected to the treatment module. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1   a  is a schematic illustration of a diafiltration delivery module and sterilizing filter configured with a dialysis machine for diafiltration treatment in accordance with one embodiment; 
         FIG. 1   b  is a schematic illustration of a diafiltration delivery module and sterilizing filter configured with a dialysis machine for diafiltration treatment in accordance with an embodiment of the invention depicting control of a pinch valve located on the infusion line between the sterilizing filter and the extracorporeal circuit; 
         FIG. 1   c  is a schematic illustration of a diafiltration delivery module, sterilizing filter, and dialysis machine configured for rinsing or disinfection in accordance one embodiment; 
         FIG. 1   d  is a schematic illustration of a diafiltration delivery module and dialysis machine configured for rinsing or disinfection without the sterilizing filter in accordance with one embodiment; 
         FIG. 1   e  is a schematic illustration of a diafiltration delivery module and sterilizing filter in a standalone configuration for testing and disinfection purposes in accordance with one embodiment; 
         FIG. 1   f  is a schematic illustration of a diafiltration delivery module and sterilizing filter in a standalone configuration for disinfect dwell or storage purpose in accordance with one embodiment; 
         FIG. 1   g  is a schematic illustration of a diafiltration delivery module in a standalone configuration for disinfect dwell or storage purpose without a sterilizing filter in accordance with one embodiment; 
         FIG. 2  is a schematic illustration of a diafiltration delivery module and sterilizing filter configured with a dialysis machine for diafiltration treatment in accordance with an embodiment of the invention using a flow switch and pressure transducers as feedback control inputs for the substitution pump; 
         FIG. 3  is a schematic illustration of a diafiltration delivery module and sterilizing filter configured with a dialysis machine for diafiltration treatment in accordance with an embodiment using temperature decay as feedback control inputs for the substitution pump; 
         FIG. 4  is a schematic illustration of a diafiltration delivery module and sterilizing filter configured with a dialysis machine for diafiltration treatment in accordance with an embodiment using a tachometer positioned on the blood pump as a feedback control input for the substitution pump; 
         FIG. 5  is a schematic illustration of a diafiltration delivery module and sterilizing filter configured with a dialysis machine for diafiltration treatment in accordance with an embodiment using a photodiode array to monitor fluid level fluctuations in a drip chamber as a feedback control input for the substitution pump; 
         FIG. 6  is a schematic illustration of a diafiltration delivery module and sterilizing filter configured with a dialysis machine for diafiltration treatment in accordance with an embodiment using an inductive means to monitor electrical currents supplied to a dialysis machine valve and blood pump as feedback control inputs for the substitution pump; 
         FIG. 7   a  is a schematic illustration of a diafiltration delivery module and sterilizing filter configured with a dialysis machine for diafiltration treatment in accordance with one embodiment using a vibration sensing device to monitor blood pump rotations as a feedback control input for the substitution pump; 
         FIG. 7   b  is a schematic illustration of a diafiltration delivery module and sterilizing filter in a standalone configuration for testing and heat disinfection purposes in accordance with the embodiment; 
         FIG. 7   c  is a schematic illustration of a diafiltration delivery module in a standalone configuration for disinfect dwell or storage purpose without a sterilzing filter in accordance with an embodiment; 
         FIG. 8  is a schematic illustration of a diafiltration delivery module and sterilizing filter configured with a dialysis machine for diafiltration treatment in accordance with an embodiment using a occluding type substitution pump located on the infusion line between the sterilizing filter and the extracorporeal circuit; 
         FIG. 9  is a schematic illustration of a diafiltration delivery module and sterilizing filter configured with a dialysis machine for diafiltration treatment in accordance with an embodiment that provides filtration of dialysate through a first filter stage and uses an adjustable throttling valve to control the rate of substitution fluid; 
         FIG. 10   a  is a schematic illustration of a treatment module portion of a diafiltration delivery module and a sterilizing filter configured with a dialysis machine for diafiltration treatment in accordance with an embodiment; 
         FIG. 10   b  is a schematic illustration of a treatment module portion of a diafiltration delivery module and a sterilizing filter configured with a dialysis machine for diafiltration treatment in accordance with an embodiment that provides filtration of the dialysate fluid prior to entering the dialyzer; and 
         FIG. 10   c  is a schematic illustration of a diafiltration delivery module and a sterilizing filter in a standalone configuration whereby the diafiltration delivery module is composed of a treatment module portion and reuse/test module portion in accordance with an embodiment. 
     
    
    
     DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS 
     In the embodiment of  FIG. 1   a , blood to be cleaned  20  is pumped by a blood pump  26  and enters a dialyzer cartridge  10 . As shown in  FIG. 1   a , inlet blood circuit pressure may be measured upon exiting blood pump  26  by use of an arterial drip chamber  22  in the blood circuit between the pump  26  and the dialyzer cartridge  10 . As known in the art, drip chamber pressure may be measured via a pressure monitoring line  21  that extends from the drip chamber  22 . The monitoring line  21  is connected to a transducer protector  25  that is connected to a pressure monitoring port  27  on the dialysis machine. Connected to the pressure monitoring port  27  is a pressure transducer  24  that is used to measure the pressure in the drip chamber  22 . The blood carrying tubing, known in the art as an arterial bloodline, may be made of a flexible polyvinylchloride (PVC) tubing. The blood flow rate is generally in the range of about 200 to about 700 ml/min, preferably 300 to 600 ml/min. 
     Dialyzer cartridge  10  contains a semi-permeable membrane  16  that divides the dialyzer cartridge  10  into a blood compartment  14  and a dialysate compartment  12 . As blood passes through the blood compartment  14 , plasma water containing blood substances may be filtered across the semi-permeable membrane  16 . Additional blood substances are transferred across the semi-permeable membrane  16  by diffusion which is induced by a difference in concentration between the blood compartment  14  and the dialysate compartment  12 . The dialyzer cartridge  10  used may be of any type suitable for hemodialysis, hemodiafiltration, hemofiltration, or hemoconcentration, as are known in the art. Preferably, the dialyzer cartridge  10  contains a medium or high flux membrane. Examples of suitable cartridges  10  include but are not limited to the Fresenius F60, Baxter CT 110, Hospal Filtral 16, or Minntech Hemocor HPH 1000. 
     Diafiltered blood exiting dialyzer cartridge  10  flows through a second blood carrying tubing, known in the art as a venous bloodline. The venous bloodline may use a drip chamber  32  as a means to measure blood circuit pressure downstream of the dialyzer cartridge  10 . In a similar fashion to the arterial bloodline, pressure is measured via a monitoring line that is connected to a pressure transducer  35  that is connected to a pressure monitoring port  37 . Connected to the pressure monitoring port  37  is a pressure transducer  34  that is used to measure the pressure in the venous drip chamber  32 . As shown in  FIG. 1   a , substitution fluid that has been generated by a diafiltration delivery module  100  is introduced into the venous drip chamber  32  at connector  90  which is in fluid communication with conduit  82  via connector  70 . This configuration is known in the art as a post-dilution diafiltration mode. It should be understood by those skilled in the art that the substitution fluid may be introduced into any suitable connection of the blood circuit. For example, it may be introduced into the arterial drip chamber  22  in a pre-dilution diafiltration mode, or if two dialyzers are used in series, it may be introduced in a mid-dilution mode (i.e. in a post-dilution mode relative to the first dialyzer and pre-dilution relative to the second dialyzer). 
     Fresh dialysate solution  50  prepared by the dialysis machine may be accomplished using any method known in the art, for example the volumetric proportioning method used in the Fresenius 2008 dialysis machine, available from Fresenius, Lexington, Mass., USA. Dialysate fluid is conveyed to a flow balancing system  54  via fluid path  52 . The flow balancing system  54  may include any suitable devices known in the art, for example, volumetric balance chambers as used in the Fresenius 2008 dialysis machine, or dual flow meters as used in the Baxter 1550 dialysis machine, available from Baxter, Deerfield, Ill., USA. Fresh dialysate from the flow balance system  54  flows through a conduit  56  that leads to the diafiltration delivery module  100 . Connection to the diafiltration delivery module  100  is accomplished by connecting the dialysis machine Hansen connector  91  to a suitable mating port  102  on the diafiltration delivery module  100 . The fresh dialysate solution generally flows through a conduit  120  of the diafiltration delivery module  100  and exits the module via conduit  130  that connects to the inlet dialysate port  15  of the dialyzer cartridge  10  via connector  104 . As will be described later, conduit  130  may be detachable from the diafiltration delivery module by use of a connector  85  and connector port  81 . Spent dialysate exits the dialyzer cartridge  10  though a dialysate outlet port  17  and flows through a conduit  40  that is connected to the dialysate port  17  via a Hansen connector  93  as known in the art. The spent dialysate, which may be considered a mixture of dialysate, plasma water, and blood toxins that have crossed the semi-permeable membrane  16  of the dialyzer cartridge  10 , is returned to the flow balancing system  54  via a dialysate pump  42 . For ultrafiltration control purposes, a UF pump  44  may be used to bypass the flow balancing system as a means to remove a specified volume of fluid from the patient during the treatment. The dialysis machine generally includes a series of valves, such as indicated by valves  51 ,  53 , and  55 , that are used to shunt or divert dialysate away from the dialyzer. This is commonly known in the art as a “bypass mode” or a “cartridge isolate mode”. 
     To generate sterile substitution fluid “online”, a portion of the fresh dialysate fluid flowing through conduit  120  of the diafiltration delivery module  100  is drawn off by a substitution pump  62  via conduit  64 . This portion of dialysate is pumped into conduit  360  that leads to the sterilizing filter  92  (indicated as “Substition Fluid Filter” in  FIG. 1   a ). As shown, the substitution filter may include redundant sterilizing filters that are connected in a series arrangement as an extra safety precaution (i.e. should one of the filters fail during the treatment). The function of the substitution fluid filter  92  is to remove bacteria, endotoxins, and particulate from the dialysate fluid to render it suitable for injection into the blood circuit. After the dialysate fluid is passed through the substitution fluid filter  92 , it flows through a flexible tubing conduit  82  that is connected to the blood circuit via connector  70 . The flexible tubing  82  may be positioned in a solenoid actuated pinch valve  84  and an optical blood detector  382  which are used as a means to prevent the substitution fluid filter  92  from being contaminated by blood from the blood circuit. This will be described in further detail as part of the operational description of the invention. 
     Basic operation of the diafiltration delivery module during a diafiltration treatment is further described with reference to  FIG. 1   a  and  FIG. 1   b  which illustrate different control aspects of an embodiment of the invention. For example,  FIG. 1   a  illustrates the feedback control mechanism used to control the substitution pump  62 , whereas  FIG. 1   b  illustrates the feedback control mechanism used to control the pinch valve  84 . 
     In  FIG. 1   a , three inputs may be used as feedback control inputs to a control unit  110  that drives the speed of the substitution pump  62 . These include a dialysate flow meter  68  that monitors dialysate flow rate through conduit  120 , a blood flow meter  262  that monitors blood flow rate through the extracorporeal circuit, and a pre-substitution pump pressure transducer  60  that monitors inlet pressure of the substitution pump  62 . The flow meter  68  may be of any type suitable for liquid flow, such as turbine flow meters, fixed volume metering chambers, mass flow meters, or thermal flow meters. In terms of the blood flow meter  262 , this may be, but is not limited to, an ultrasonic flow meter device such as available from Transonic Systems, Ithica, N.Y., USA. In order for the substitution pump to be turned ON, at least two conditions must be met. First, an adequate dialysate flow rate must be sensed by the dialysate flow meter  68  and second, an adequate blood flow rate must be sensed by the blood flow meter  262 . This assures that the machine is not in a bypass mode and that there is a sufficient amount of blood flowing through the dialyzer  10  to prevent over hemoconcentration during the diafiltration process. The third control input, dialysate pressure measured via pressure transducer  60 , may be used as a back up control input to turn the substitution pump OFF when a specified negative pressure is detected. For example, if either of the flow meters  68 ,  262  failed during the treatment or the substitution pump ran at an excessive uncontrolled rate, a negative pressure would be detected by the pressure transducer  60 . This would then be used to signal the control unit  110  to disable the substitution pump  62  and place the diafiltration delivery module in a safe state. It should be apparent to those skilled in the art that the invention thus prevents unsafe or hazardous conditions that can occur when the blood pump  26  on the dialysis machine stops circulating blood through the extracorporeal circuit or when the dialysis machine stops delivering dialysate fluid  50  to the dialyzer  10 . 
     In  FIG. 1   b , three inputs may be used as feedback control inputs to the control unit  110  that control the position of the pinch valve  84 . These include a control signal from the substitution pump  62  to indicate it is ON and pumping, a pressure transducer  66  that monitors the downstream pressure of the substitution pump  62 , and an optical blood sensor  382  that monitors the transmittance of the fluid contained in the substitution fluid tubing conduit  82 . The optical sensor can be of any suitable type that includes a light source and a photo-detector combination to detect a loss of transmittance of light through the fluid contained in the tubing. In order for the pinch valve  84  to be opened, at least two conditions must be met. First, the substitution pump  62  must be turned ON and pumping dialysate fluid in the direction of the substitution fluid filter  92 . Second, a minimum pressure sensed by pressure transducer  66  must be achieved that assures that substitution flow will remain in the forward direction into the extracorporeal circuit when the pinch valve  84  is opened. A third control input from the optical sensor  382  may be used as a back up control input to close the pinch valve  84  and place the diafiltration delivery module in a safe state whenever blood is detected in the substitution fluid tubing conduit  82 . Here it should be apparent to those skilled in the art that the invention prevents blood from backing up into the substitution filter  92  and thus enabling the substitution filter  92  to be used multiple times for several treatments without the risk of cross contamination between patients. Again, we may want to refer to our other patent covering the valve mechanism for infusion fluid system. 
     Operation of the diafiltration delivery module  100  to deliver a fluid bolus during treatment is described as follows with reference back to  FIG. 1   a . In order to use the diafiltration delivery module  100  in a fluid bolus mode, the user will be instructed to place the dialysis machine in a bypass or cartridge isolate mode. This necessary to assure proper fluid balance is maintained during the course of giving the fluid bolus. Once the dialysis machine is placed in a bypass or cartridge isolate mode, such as achieved by closing valves  51  and  55  and opening valve  53 , the dialysate flow through the diafiltration delivery module  100  will stop. Upon detecting there is no dialysate flow by flow meter  68 , the diafiltration delivery module is automatically placed in a safe state (i.e. substitution pump  62  is turned OFF, pinch valve  84  is closed, and all valves including  372  is closed). Next, the substitution pump  62  is turned ON and thereafter valve  370  can be opened once a negative pressure is sensed at pressure transducer  60 . The negative pressure condition assures fluid will not leak out of the module when valve  370  is opened to atmospheric pressure. As the substitution pump  62  continues to pump, air will enter through connector  81  and flow through conduit  364  leading to a fluid reservoir  300  that contains a source of dialysate fluid. The dialysate fluid from the reservoir  300  flows into conduit  120  and subsequently into conduit  64  leading to the substitution pump  62 . On the discharge side of the substitution pump  62 , pressure will increase since pinch valve  84  is in a closed positition. Once a minimum pressure is achieved, the pinch valve  84  may be opened to allow substitution fluid to flow through conduit  82  and into the extracorporeal circuit. Provided the substitution pump  62  is a metering type pump, a specified volume of bolus fluid can be given based on pumping a certain number of strokes. If the substitution pump is not a metering type pump, it may be necessary for the user to monitor the amount of fluid given based on a visual observation of fluid level changes in the fluid reservoir  300 . The means to provide substitution fluid for priming and rinseback are similar to that described above with the exception that the point of entry of substitution fluid into the extracorporeal circuit may be changed to a different location to achieve the best results. 
     Reference is now made to  FIG. 1   c  which shows schematic illustration of a diafiltration delivery module  100  and the substitution filter  92  that has been configured for rinsing or disinfection in conjunction with the dialysis machine. Here the extracorporeal circuit and substitution fluid tubing conduit  82  have been removed and the associated dialysate female Hansen connectors  104  and  93  have been placed on their respective dialysis machine rinse ports  404  and  402  respectively. The dialysate conduit  130  with end connector  85  is placed on a mating rinse port  83 . A substitution filter rinse line, which is made up of tubing conduits  410  and  416  connected in a tee configuration with associated end connectors  414 ,  418 , and  412 , is connected to rinse ports  81 ,  346 , and substitution outlet port  79  respectively. Operation of the diafiltration delivery module during a machine rinse or disinfect cycle is as follows. The dialysis machine produces a source of fluid  49  that can be used for rinsing, disinfecting, or priming the fluid path of both the dialysis machine and the diafiltration delivery module  100 . Fluid from the fluid source  49  is conveyed through conduit  52  to the flow balance system  54 . From the flow balancing system  54 , the fluid flows through conduit  56  and into the diafiltration delivery module  100  via connector  102 . Generally, the fluid runs through the diafiltration delivery module  100  through conduit  120  and into the bottom of the fluid reservoir  300 . The outlet of the reservoir  300  is located at the top so that air within the fluid reservoir  300  is effectively purged out through conduit  364  during the initial part of the cycle. Fluid exiting the diafiltration delivery module is returned to the dialysis machine through conduit  130  which is attached to the dialysis machine rinse block connector  404 . In order to rinse or disinfect the remaining fluid path portions of the diafiltration delivery module  100  and substitution fluid filter  92 , the dialysate flow meter  68  is monitored to ensure an adequate flow of fluid is passing through the module  100 . When an adequate flow has been determined, the substitution pump  62  can be turned ON to initiate flow through conduit  64  and conduit  360  leading to the substitution fluid filter  92 . By selectively opening and closing valves, it is possible to direct the fluid though select portions of the fluid path. For example, by closing valves  97 ,  95 ,  99 , and  87  and opening valve  372 , one can direct fluid across the substitution fluid filter  92  and through conduit  410  that leads back to the fluid reservoir  300 . By closing valve  372  and opening valve  87 , one can direct fluid through a first filter stage of the substitution fluid filter  92  and though a conduit  366  that leads back to the fluid reservoir  300 . By closing valve  87  and opening valves  97  and  372 , one can direct a portion of fluid from the substitution pump into conduit  368  and through conduit  416  that leads to conduit  410  in fluid communication with the fluid reservoir  300 . By closing off valve  372  and opening valves  95  and  99 , one can direct flow from conduit  368  into conduits  342  and  362  that is in fluid communication with the fluid reservoir  300 . It should be apparent to those skilled in the art that the fluid path of the diafiltration delivery module  100  does not contain any dead legs and as such can be properly primed, rinsed, disinfected because one can expose the entire fluid path to dialysate for the purpose of priming, water for the purpose of rinsing, or a disinfectant solution for the purpose of disinfection. 
     Reference is now made to  FIG. 1   d  that illustrates the configuration when the substitution filter  92  and its associated rinse line has been separated from the diafiltration delivery module  100 . Here, rinse line connectors  414  and  418  are detached from the diafiltration module while connectors  350  and  150  are detached from the substitution fluid filter. Connectors  150 ,  350 ,  414 ,  418  are then reconnected as follows. Connectors  414  and  418  are attached to the substitution filter ports  77  and  348  respectively. Connectors  150  and  350  are attached to the diafiltration delivery module ports  81  and  346  respectively. Operation of the diafiltration delivery module  100  in this configuration is similar to that described above with reference to  FIG. 1   c . For example, the dialysis machine produces a source of fluid  49  that can be used for rinsing, disinfecting, or priming the fluid path of both the dialysis machine and the diafiltration delivery module  100 . Valves may then used to direct flow through different sections of the diafiltration delivery module fluid path as a means to fully expose the fluid path with the dialysis machine source fluid  49 . Also, it should be apparent to those skilled in the art, that the rinse line (made up of conduits  410  and  416  and connectors  412 ,  414 , and  418 ) helps contain fluid within the substitution fluid filter cartridge  92 . This can be advantageous with respect to storage of the filter between uses, for example if it has been filled with a disinfectant solution that requires a dwell period as part of the disinfection procedure. 
     Reference is now made to  FIG. 1   e  showing a diafiltration delivery module and substitution fluid filter cartridge that has been configured in a standalone mode for testing and disinfection. The differences between this configuration and that shown in  FIG. 1   c  is as follows. Dialysis machine connector  91  has been detached from the diafiltration delivery module inlet port  102 . The diafiltration module connector  104  has been detached from the dialysis machine rinse block port  404  and is subsequently connected to the diafiltration module inlet port  102 . A diafiltration module shunt connector, which is made up of conduit  342  with appropriate end connecors that attach to module disinfection ports  89  and  344 , is removed and tubing conduits  474  and  476  with end connectors  480  and  482  are attached to the diafiltration module disinfection ports  89  and  344  respectively. These conduits lead to either a single reservoir  492  or two reservoirs  470  and  472  respectively. For the case of a single reservoir  492 , this reservoir holds a disinfection solution  490  and may contain heating element  494  as a means to perform a heat disinfection step. For the case of the two reservoirs, reservoir  472  holds a disinfection solution, while reservoir  470  serves primarily as a fluid collection vessel. Operations for carrying out various tests and disinfection routines are described in the following paragraphs. 
     In the standalone configuration, the diafiltration delivery module  100  may perform a fluid path integrity test to verify that the fluid path and connections to the substitution filter are intact. This may be accomplished by closing valves  87 ,  95 ,  99 , and  372 , while opening valves  97  and  370 . The substitution pump  62  may then be turned ON in the forward direction for a period of time or until a certain pressure is observed at the discharge pressure transducer  66 . Here, a positive pressure generally develops in the substitution filter cartridge  92  while a negative pressure is generated in the fluid reservoir  300 . At the end of the pressurizing period, the substitution pump  62  may be turned OFF and, after a specified stabilization period, the control unit  110  may monitor the rate of pressure decay over a set test period. Any fluid path leaks may then be detected when the measured pressure decay exceeds a pre-determined limit. Similarly, a second integrity test may be performed with the substitution pump  62  operated in reverse direction. Here, a positive pressure generally develops in the fluid reservoir  300 , while a negative pressure is generated in the substitution filter cartridge  92 . 
     Next, a water permeability test may be performed as a means to monitor the degree of plugging of the substitution fluid filter  92 . This may be accomplished by running the substitution pump  62  in the forward direction at a specified rate with all valves closed except for valve  372 . Fluid then runs from the substitution pump  62 , through conduit  360 , across the substitution filter  92 , through conduit  410 , into conduit  120 , and finally through conduit  64  where it is returned to the substitution pump  62 . By monitoring pressures at pressure transducers  60  and  66 , one may determine the degree of plugging by comparing the resulting pressure differential relative to that of a new substitution filter. 
     A substitution filter membrane integrity test may also be performed. As shown in  FIG. 1   e , the substitution filter  92  may be comprised of a first sterile filter stage  520  and a second filter stage  522 . The first filter stage  520  contains a semi-permeable membrane  521  that divides the first filter stage into a first upstream compartment  524  and a first downstream compartment  526 , while the second filter stage  522  contains a semi-permeable membrane  523  that divides the second filter stage  522  into a second upstream compartment  528  and a second downstream compartment  530 . The substitution filter  92  is configured such that is includes a port  348  that is in fluid communication with both the first downstream compartment  526  and the second upstream compartment  528 . Membrane integrity testing of both filter stages may be accomplished simultaneously as follows. First, valves  372 ,  370 , and  87  are closed while valves  99 ,  95 , and  97  are opened. The substitution pump  62  is turned ON in the forward direction. A negative pressure ensues in fluid reservoir  300  that in turn draws air into conduit  474  and into conduit  362 . Air enters the reservoir  300  and displaces the fluid initially contained in the reservoir such that it becomes partially full. The fluid from the reservoir  300  travels through conduit  120 , into conduit  64 , into parallel conduits  368  and  360 . A portion of the fluid flows though conduit  360 , across the substitution fluid filter  92  and into conduit  416 . The other portion of fluid flows through conduit  368  and combines with the fluid from conduit  416 . This fluid then flows through valve  95 , into conduit  476  and finally into the fluid reservoir  472 . After a specified amount of fluid has been pumped into the fluid reservoir  472  and before the fluid in reservoir  300  is emptied, the substitution pump is turned OFF. Next, valve  87  is opened and valve  95  is closed. The substitution pump  62  is turned on in the reverse direction such that a negative pressure is simultaneously generated at the inlet and outlet ports,  77  and  79 , of the substitution filter  92 . This will in turn draw fluid across both filter membranes  521  and  523  such that fluid flows from the first downstream compartment  526  into the first upstream compartment  524  and from the second upstream compartment  528  into the second downstream compartment  530 . Because the first downstream compartment  526  and the second upstream compartment  528  are in fluid communication with the top of the fluid reservoir  300  via conduit  366 , air in the top of the partially full fluid reservoir  300  will flow into conduit  366  and eventually into the filter compartments  526  and  528 . When the fluid in compartments  526  and  528  is completely displaced by the air, the negative pressure as sensed by pressure transducer  66  should become more negative since air should not be able to cross the semi-permeable membranes  521  and  523 , assuming they are intact. Upon reaching a specified negative pressure, the substitution pump  62  may be turned OFF provided it is an occluding type pump. After a specified stabilization period, the control unit  110  may monitor the rate of pressure decay over a set test period. Any substitution filter integrity leaks may then be detected when the measured pressure decay exceeds a predetermined limit as is known in the art as a pressure decay test. Upon passing the pressure decay test, refilling the substitution filter compartments  526  and  528  with fluid may be accomplished by turning on the substitution pump  62  in the forward direction such that fluid from the fluid reservoir  300  is drawn into conduit  120 , into conduit  64 , and through conduits  360  and  368  which lead to the substitution filter compartments  524  and  530 . This will force fluid across the semi-permeable membranes  521  and  523  and into compartments  526  and  528  respectively, and thus push the air back into the fluid reservoir  300 . 
     With continued reference to  FIG. 1   e , the diafiltration delivery module  100  with the accompanying substitution filter  92  may be loaded with a disinfectant solution for disinfection of the fluid path and substitution filter  92 . For a chemical disinfection, a concentrated disinfecting solution  478  may be placed into the fluid reservoir  472 . This fluid is drawn into the fluid path by opening valves  95 ,  97  and  99 , closing valves  87 ,  370  and  372 , and turning on the substitution pump  62  in the reverse direction with flow leading into conduit  64 . Provided the substitution pump  62  is an occluding type pump, such as a metering pump, a specified volume of concentrated disinfecting solution  478  can be pumped into the fluid path. In addition, the fluid reservoir  300  may be filled by purging air out the top through conduit  362  that leads the fluid reservoir  470 . Next, by opening and closing various valves in the fluid path, the concentrated disinfecting solution can be mixed with the fluid contained in the fluid path such that a uniform concentration can be achieved and such that all sections of the fluid path can be exposed to the resulting disinfecting solution. For example, with the substitution pump  62  turned ON in the forward direction, conduits  360 ,  410 ,  120 , and  64  can be exposed with valve  372  opened and all others closed. Next, opening valve  97  additionally exposes conduit  416  to the disinfecting solution. By closing valves  372  and  97  and opening valve  87 , conduits  360 ,  366 , fluid reservoir  300 , and conduits  120  and  64  may be exposed to the disinfecting solution. Next, opening valve  370  additionally exposes conduits  364 ,  130 , and  120 . As an alternative to a purely chemical disinfection process, one may configure conduits  474  and  476  such that they are both in fluid communication with a common fluid reservoir  492  which includes an electrical heating element  494 . In this configuration, the fluid  490  contained in reservoir  492  may be pure water or may be a dilute citric acid/water solution (for example containing about 1% to 5% citric acid by weight). In a similar manner as above, by opening and closing various valves and by turning substitution pump  62  ON in the reverse direction, one may draw heated fluid from reservoir  492  into conduits  476  and  368  and pump this heated fluid through conduits  64  and  120  and into fluid reservoir  300 . Next the heated fluid can be recirculated throughout the fluid path the same as described above. The main difference to the chemical disinfection process is that one may need to repeatedly draw heated fluid into the fluid path in order to maintain a minimum temperature during the heat disinfection process. 
     Reference is now made to  FIG. 1   f  that shows the diafiltration delivery module  100  with a substitution fluid filter  92  that has been configured in a self contained mode suitable for storage or chemical dwell periods as part of a fluid path disinfection process. This configuration is similar to that of  FIG. 1   e  except conduits  474  and  476  have been removed from ports  89  and  344  respectively and replaced with the diafiltration module shunt connector containing conduit  342 . 
     Reference is now made to  FIG. 1   g  that shows the diafiltration delivery module  100  in a self contained mode after the substitution fluid filter  92  and its associated rinse line have been removed. This configuration is also suitable for storage or chemical dwell periods as part of a fluid disinfection process. This configuration is similar to that of  FIG. 1   f  except connector  150  is attached to port  81  and connector  350  is attached to port  346 . 
     A second embodiment of the invention is described with reference to FIG.  2 . The difference between this embodiment and the first embodiment is the manner in which dialysate flow and blood flow is sensed by the diafiltration delivery module  100 . Here, dialysate flow rate is sensed by flow switch  264  instead of flow meter  68 . The flow switch  264 , may be a thermal flow switch, such as supplied by Intek, Inc., Wattersville, Ohio or a mechanical flow switch, such as supplied by Dwyer Instruments, Inc., Michigan City, Ind. The state of the flow switch  264 , either ON or OFF, is then used as a control input to the control unit  110  to either enable or disable operation of the substitution pump  62 . For blood flow sensing, one may detect when the blood pump  26  is ON or OFF by detecting the occurrence of pressure pulses in the extracorporeal circuit as the result of the peristaltic nature of the roller type blood pump  26 . Two means of detecting pressure pulses may be used. First, as shown in  FIG. 2 , one may use a pressure transducer  132  that is in fluid (air) contact with one of the drip chamber pressure monitoring ports, such as the arterial pressure monitoring port  27  of the dialysis machine. This may be accomplished by inserting a tee device  136  between the monitoring port  27  and the disposable transducer protector  25 . The tee  136  is connected to a conduit  134  that leads to a pressure transducer  132  located within the diafiltration delivery module  100 . Second, an alternative to this configuration is a surface mounted pressure transducer  137  that is in direct contact with a portion of the bloodline tubing, such as tubing segment  28 . The surface mounted pressure transducer  137  may be mounted in tubing clip such that the flexible tubing is partially flattened against the surface of transducer for better sensing of pressure pulses. An example of a surface pressure transducer is the Model AB transducer available from Data Instruments, Inc. Acton, Mass. For control purposes, the time interval between successive pressure pulses can be used as a feedback control input to the control unit  110 . If no pulses are detected, or if the time period waiting for a next pulse exceeds a pre-set value, the substitution pump  62  can be turned OFF and the system put in a safe state. It should be apparent to those skilled in the art that this embodiment also overcomes the safety issues described above when either blood or dialysate flow is stopped during treatment while having a distinct advantage over the first embodiment using flow meters in that the cost can be reduced significantly. 
     A third embodiment of the invention is illustrated in  FIG. 3  which uses temperature decay measurements for monitoring dialysate flow rate and blood flow rate as opposed to flow meters, flow switches, or pressure transducers. Again operation is similar to the first embodiment with exception to the following. Dialysate and blood flow is indirectly measured using a temperature sensing device, such as thermistor, thermocouple, or infrared temperature sensor as are known in the art. For dialysate flow, the temperature sensing device  69  may placed in the fluid stream, such as a thermistor placed in conduit  120  or may be placed external to the fluid stream, such as an infrared temperature sensor that monitors the external surface of conduit  120 . Since the dialysis machine supplies dialysate fluid at a controlled temperature, one can monitor the dialysate fluid temperature as a means to detect when the dialysis machine stops delivering fluid to the diafiltration delivery module, such as can occur when the machine goes into bypass. For example, if dialysate flow into the diafiltration delivery module  100  is interrupted, the fluid temperature within the module  100  will begin to cool. This decay in temperature, which may be determined simply as a change in temperature from a fixed set point (temperature decay) or as a change in temperature per unit time (decay rate), may then be used as a feedback control input to the control unit  110  that drives the substitution pump. For blood flow sensing, a blood temperature sensing device  280  may be used to monitor the extracorporeal circuit blood temperature. This may be accomplished by using a thermistor or thermocouple that is placed in direct contact with the outside surface of the blood tubing, such as accomplished by mounting the thermistor in a tubing clip that is affixed to the bloodline tubing or by using a non-contacting infrared temperature sensor that is directed at the blood tubing surface. By positioning the blood temperature sensing device  280  near the blood outlet of the dialyzer  10 , such as the bloodline tubing segment  540 , one can take advantage of the dialysis machine&#39;s ability to control the dialysate temperature. For example, blood temperature exiting dialyzer  10  should be substantially equal to the inlet dialysate temperature as the dialyzer  10  acts as an efficient heat exchanger. Again, since the dialysis machine supplies dialysate fluid at a controlled temperature, the blood temperature exiting the dialyzer will trend similarly with dialysate temperature. If the blood pump  26  stops in response to an alarm condition or is reduced to a low rate by the user, the blood in the extracorporeal circuit (excluding the dialyzer  10 ) will begin to cool. This decay in temperature, which may be determined simply as a change in temperature from a fixed set point relative to the dialysate temperature (temperature decay) or as a change in temperature per unit time relative to the dialysate temperature (decay rate), may then be used as a feedback control input to the control unit  110  that drives the substitution pump. Similarly to the above embodiments, it should be apparent to those skilled in the art that the system can be placed in a safe state in the event that either dialysate flow or blood flow is interrupted during operation of the invention. 
     Reference is now made to  FIG. 4  which shows yet another embodiment of the invention. In this embodiment, blood flow is sensed using a tachometer device  270  that measures the rotational speed of the blood pump  26 . An example of a tachometer  270  that can be used is a non-contacting phototachometer such as supplied by Cole Parmer Instrument Company, Vernon Hills, Ill. Here, a piece of reflective tape is applied to a rotating member of the blood pump  26  while the phototachometer monitors the time interval between successive passes of the reflective tape. Operation is then similar to the second embodiment which looked at pressure pulses as a means to sense blood flow. 
     In a fifth embodiment of the invention, with reference now being made to  FIG. 5 , blood flow sensing is accomplished using a linear photodiode array  272 , such as supplied by Integrated Vision Products AB, Linkoping, Sweden. The linear photodiode array  272  is positioned near one of the drip chambers, preferably the arterial drip chamber  22  of the extracorporeal blood circuit, such that it can be used to monitor relative changes in fluid level. For example, one may detect when the blood pump  26  is ON or OFF by detecting the occurrence of fluid level fluctuations in the drip chamber  22  as the result of the peristaltic nature of the roller type blood pump  26 . For control purposes, the signal from the linear photodiode array  272  is sent to the control unit  110  as a feedback control input. If no fluid level fluctuations are detected, the substitution pump  62  can be turned OFF and the system put in a safe state. 
     Reference is now made to  FIG. 6  showing a sixth embodiment of the invention. In this embodiment, dialysate and blood flow are indirectly sensed by inductively monitoring the current supplied to the inlet dialysate valve  51  and the motor that drives the blood pump  26 . This may be accomplished by placing inductive current clamps  162  and  108  around the wires leading to the dialysate inlet valve  51  and the blood pump  26  respectively. An example of an inductive current clamp that can be used is the Fluke DMM current clamp supplied by Techni-Tool, Plymouth Meeting, Pa. Control of the diafiltration delivery module  100  may then accomplished by using the signals from the inductive current clamps  162  and  108  as feedback control inputs to the control unit  110 . If a current is sensed flowing through the dialysate inlet valve  51  and through the blood pump  26 , it can be assumed dialysate flow is passing through the diafiltration delivery module  110  and that blood flow is flowing through the extracorporeal circuit. When current is not detected by either inductive current clamp  162  or  108 , the substitution pump  62  is turned OFF and the system is placed in a safe state. 
     In a seventh embodiment of the invention, with reference to  FIG. 7   a , a blood flow is indirectly sensed by detection of blood pump vibrations that occur when the peristaltic blood pump repeatedly compresses the blood pump segment with a roller mechanism as it rotates. Typically, the roller mechanism in the pump head is spring loaded such that the spring becomes more compressed during a portion of each blood pump rotation (i.e. when contacting the blood pump segment). Blood pump vibrations may be detected mechanically or acoustically. To detect vibrations mechanically, one may use a vibration transducer  710  that is in physical contact with the dialysis machine, preferably near the blood pump with the transducer axis lining up with the radial direction of the blood pump. An example of a vibration transducer that may be used is the A-118 vibration transducer available from CEC Vibration Products, Covina, Calif. To detect vibrations acoustically, one may use a sound detection device  712 , such as a microphone, that in effect picks up sound vibrations from the blood pump as it rotates to propel blood through the extracorporeal circuit. When vibrations that are characteristic of blood pump rotation are not detected by either the vibration transducer  710  or the sound detection device  712 , the substitution pump  62  is turned OFF and the system is placed in a safe state. 
     With continued reference to  FIG. 7   a , another aspect of the invention is shown whereby a check valve  699  is used in place of the optical blood sensor  382  described in the earlier embodiments. The check valve  699  is disposed in the infusion line conduit  82  that carries substitution fluid from the substitution fluid filter  92  to the extracorporeal circuit. The check valve  699 , which permits flow in only one direction, serves to provide a secondary mechanism to prevent blood in the extracorporeal circuit from contaminating the substitution fluid filter  92 . This together with the control aspect of the pinch valve  84  provide redundant safety mechanisms to prevent cross-contamination via the substitution filter and therefore enables the substitution filter to be used multiple times with different patients. 
     Another aspect of ths embodiment is shown with reference to  FIG. 7   b . Here the diafiltration module  100  has been placed in a standalone configuration with the substitution fluid filter  92  remaining with the module for testing and disinfection. An advantage of this embodiment over the previous embodiment shown in  FIG. 1   e  is that it does not require attachment of any additional fluid reservoirs (Such as  490 ,  470 , and/or  472 ) to carry out the respective filter tests and disinfection procedures. Examples of how the various tests and disinfection procedures may be carried out are as follows. Priming of a new substitution filter is accomplished first by opening a water inlet valve  566  to introduce water from a source  572  which is typically an AAMI quality water as is known in the art. The water is then filtered through a water filter  600  that contains a semipermeable membrane  603 . The water filter through a water filter  600  that contains a semipermeable membrane  603 . The water filter removes bacteria, endotoxin, and other particulate that may be present in the incoming water stream. The filtered water exits the water filter  20  and passes through conduit  658 . Valve  620  is opened to allow flow of the filtered water through conduit  650  that lead to the substitution fluid filter  92 . Air in the inter-stage compartments (i.e. downstream of the first filter stage and upstream of the second filter stage) is pushed out of the filter and into conduit  682 . Opening valves  87 ,  612 , and  608  allows the air to pass out to the drain  580  via conduits  682  and  656 . Next, valve  87  is closed such that the filter water is pushed across the semi-permeable membranes  521  and  523  which displaces the air in the respective upstream compartment of the first stage and the downstream compartment of the second stage. Opening valves  97 ,  614 , and  608  then allows the displaced air to flow through conduits  360 ,  696 ,  368 , 654 ,  656  and subsequently out to the drain  580  leaving the substitution filter  92  primed with filtered AAMI quality water. Testing the integrity of the water filter  600  may be performed as follows. Opening valves  606 ,  622 ,  618 ,  614 , and  608  (all other valves being closed) and turning on the substitution pump  62  in the forward direction causes a negative pressure in the downstream compartment  604  of the water filter  600 . This draws fluid across the semi-permeable membrane 603 . To make up for the displaced fluid, air enters the fluid path through an air filter  630  and eventually fills the upstream compartment  602  of the water filter  600 . The air filter  630  may be a hydrophobic filter as is known in the art and is used to prevent bacteria from entering into the fluid path of the module. The fluid being discharged by the substitution pump  62  flows out through conduits  654  and  656  that lead to the drain  580 . After the water has been displaced from the upstream compartment  602 , a negative pressure will build up in the conduit  660  leading to the substitution pump as air will not be able to pass through the water filter membrane  603  (assuming the filter is intact). Upon reaching a specified negative pressure, the substitution pump is turned OFF and the negative pressure measured by pressure transducer  60  may be monitored for pressure decay as discussed previously to verify integrity of the water filter. Integrity of the substitution filter may also be tested in a similar manner. For example, this may be accomplished by opening valves  622 ,  87 ,  97 ,  616  and  608  (all other valves closed) and turning ON the substitution pump  62  in the reverse direction. Here, air enters through the air filter  630  and displaces the water in conduit  682  and in the downstream compartment of the first stage of the substitution filter and the upstream compartment of the second stage of the substitution filter. The displaced fluid from the substitution filter flows through conduits  360 ,  696  and  368  leading back to the substitution pump  62 . Fluid being discharged by the substitution pump  62  then flows through conduits  64  and  656  leading out to the drain  580 . In a similar manner as described previously, a pressure decay test is performed that simultaneously verifies integrity of both filter stages of the substitution filter  92 . Disinfection of the diafiltration module fluid path that includes both the water filter  600  and the substitution fluid filter  92  may be accomplished as follows. After priming and rinsing the fluid path with the filter water, the inlet water valve  566 , the outlet drain valve  608 , and the air vent valve  622  may be closed to seal off the fluid path from the external environment. The water inside the fluid path may then be recirculated through the module by turning ON the substitution pump  62  in the reverse direction and opening valves  620 ,  97 ,  616  and  654 . 
     Next, the water may be heated to a desired temperature as it flows by a heating element  494 . The heated water then flows through conduits  658  and  650  leading to the substitution filter  92 . The heated water then passes through the filter membranes  521  and  523  and out through conduits  360  and  696 . The temperature of the fluid exiting the substitution fluid filter may be monitored using a temperature sensor  632 . This heated water then flows through conduit  368  and combines with the heated water flowing through conduit  360  leading back to the substitution pump  62 . The discharged fluid from the substitution pump  62  then flows through conduits  64 ,  656  and  570  leading back to the upstream compartment  602  of the water filter  600 . The water is again filtered across the semi-permeable membrane  603  and back to the heating element  494 . It should be understood to those skilled in the art that manipulation of the valves of the fluid path would allow the entire fluid path of the module (excluding the water inlet line leading up to the water filter  600  and the air vent line containing the air filter  630 ) to be exposed to the heated water as a way to disinfect the module fluid path, the water filter  600 , and the substitution filter  92 . For example, to achieve a high level disinfection of the substitution filter, one may circulate heated fluid (preferable above 80° C.) for a set period of time. A chemical disinfection and/or cleaning process of the diafiltration module fluid path (without the substitution fluid filter  92 ) may be accomplished. 
     With reference to  FIG. 7   c , the substitution fluid filter  92  has been removed and replaced with a container  700  containing chemical disinfect or cleaning solution  710 . The container  700  may include a removable top  702  to allow one to reuse the container. The module  100  attaches to the container  700  by connecting connectors  350  and  640  to ports  706  and  708  respectively. Module connector  150  is attached module rinse port  346 . As discussed previously with reference to  FIG. 1   e , one may recirculate fluid within the module to achieve a uniform concentration of disinfectant in most all parts of the fluid path. Rinsing the disinfectant out of the circuit may also be accomplished using fresh water  572  with the expelled fluid being sent out to the drain  580 . 
     Reference is now made to  FIG. 8  showing an eighth embodiment of the invention. In this embodiment, an occluding type substitution pump  290  is used to deliver substitution fluid to the extracorporeal circuit. The configuration is similar to that of the first embodiment, except the substitution pump  290  has been moved to the downstream side of the substitution filter  92  and is used in place of the pinch valve. The occluding type pump  290  may be a peristaltic roller pump as is known in the art. This has the advantage of eliminating the need for the pinch valve and thus reducing the number of hardware components used in the diafiltration delivery module  100 , however, this requires a special infusion line  82  containing a pump segment that fits the roller pump  290 . Control of the substitution pump  290  is similar to that described in the above embodiments in that a means for detecting adequate flow of both dialysate and blood must be performed for safe operation of the device. In addition, one can prevent blood from contaminating the substitution filter  92  by only allowing the substitution pump  290  to turn in one direction (i.e. in the direction toward the extracorporeal circuit). 
     Reference is now made to  FIG. 9  showing an ninth embodiment of the invention which adds the feature of filtering the entire dialysate stream prior to being delivered to the dialyzer cartridge  10  at its inlet port  15 . The configuration is similar to the first embodiment ( FIG. 1   a ) with the exception that a fluid conduit  510  has been added to provide a fluid connection between conduit  366  and what was conduit  120  in the previous embodiment. In the new conduit  510 , a fluid throttling valve  502  has also been added. The throttling valve  502 , for example, may be a proportioning valve such as supplied by South Bend Controls, South Bend, Ind. Filtration of the dialysate fluid during treatment may then be accomplished as follows. Dialysate fluid from the dialysis machine flows into the diafiltration delivery module  100  and flows through conduit  120 . Initially the pinch valve  84  is closed to prevent substitution fluid from flowing out of conduit  82 . This allows the dialysate flow rate delivered by the dialysis machine to be sensed by flow meter  68 . This dialysate flow rate reading is then used as a basis for setting the substitution flow rate which is further described below. The aperture of the throttling valve  502  and the speed of the substitution pump  62  are each set to an initial setting. The substitution pump may be set such the its flow rate equals or exceeds the flow rate of the base dialysate fluid flow rate measured above. Next, the aperture of the throttling valve  502  is adjusted up or down until a pre-determined target pressure is observed at the discharge side of the substitution pump  62  via pressure transducer  66 . The target pressure should be high enough to assure that substitution fluid in conduit  82  will flow in the direction of the extracorporeal circuit when the pinch valve  84  is opened. In other words, the target pressure should be sufficiently higher than an expected blood circuit pressure. With the substitution pump  62  running, flow of unfiltered dialysate fluid from conduit  120  will flow into conduit  64 , through conduit  360 , across the first filtering stage of the substitution filter  92 . The filtered dialysate fluid then flows through conduit  550 , into conduit  510  and through the throttling valve  502 . If the flow rate through the substitution pump  62  is equal to the base dialysate flow, then all the filtered dialysate fluid flowing through conduit  510  will flow into conduit  504 . If the flow rate through the substitution pump  62  is greater than the base dialysate flow, then a portion of filtered dialysate fluid flowing through conduit  510  will flow into conduit  500 . This portion of filtered dialysate fluid is then mixed with the unfiltered dialysate from conduit  120  and recirculated back to the substitution pump  62  via conduit  64 . In this fashion, only filtered dialysate fluid will flow into conduit  504 . 
     In order to begin diafiltration, pinch valve  84  is opened to allow substitution fluid to flow from the diafiltration delivery module  100  to the extracorporeal circuit. When this occurs, the dialysate flow rate through conduit  504  will be reduced by an amount that is equal to the substitution fluid rate. By monitoring this change in dialysate flow rate, it is then possible to control substitution fluid flow rate using a feedback control loop that controls the aperture of the throttling valve  502 . For example, to increase the substitution fluid flow rate, the control unit  110  can send a signal to the throttling valve  502  to reduce its aperture setting. This will have the effect of increasing the upstream side of the substitution fluid filter  92  to force more fluid across the filter and into the extracorporeal circuit. To decrease the substitution fluid flow rate, the control unit can enlarge its aperture setting which will have the opposite effect. An additional substitution pump control scheme based on a feedback control loop using pressure transducer  66  may be used to ensure that a minimum pressure is maintained on the discharge side of the substitution pump. For example, it may be necessary to boost the speed of the substitution pump to maintain a sufficient outlet pressure to assure blood does not back up into the substitution filter when the pinch valve  84  is in the open position. 
     Reference is now made to  FIGS. 10   a ,  10   b  and  10   c  showing a tenth embodiment of the invention. In this embodiment, the diafiltration delivery module has been separated into a treatment module portion  100 A and a reuse/test module portion  100 B. In order to perform diafiltration in conjunction with a dialysis machine, only the treatment module  100 A is required as is shown in  FIGS. 10   a  and  10   b . In  FIG. 10   a , the treatment module  100 A is configured for diafiltration without filtering the dialysate stream by a first filter stage of the substitution filter  92 . In  FIG. 10   b , it is shown how to configure the treatment module  100 A such that the dialysate stream is filtered by the first filtering stage of the substitution filter  92  prior to being delivered to the dialysate compartment of the dialyzer  10 . In order to perform fluid path integrity tests, filter plugging and integrity tests, and disinfection of the substitution filter  92 , the reuse/test module  100 B is connected to the treatment module  100 A in a standalone configuration as shown in  FIG. 10   c.    
     During treatment with the treatment module  100 A, as shown in  FIG. 10   a , operation is similar to that described in the first embodiment with reference to  FIG. 1   a . For example, dialysate and blood flows are sensed via flow meters  68  and  262  respectively and if adequate, the substitution pump  62  draws a portion of the dialysate fluid stream and passes it through the substitution filter  92  before infusing into the extracorporeal circuit. It should be noted however, that the fluid reservoir  300  is not present in the treatment module  100 A, and therefore it is not possible to generate substitution fluid for priming, fluid bolus, and rinseback purposes. Also, since conduit  366  is not present as part of the treatment module  100 A, a filter cap  590  must be placed on the substitution filter  92  to prevent fluid from escaping out of the filter port  348 . 
     As illustrated in  FIG. 10   b , it is possible to configure the treatment module  100 A such that one can filter the dialysate stream through the first filtering stage of the substitution filter  92  prior to passing it through conduit  130  leading to the dialysate compartment  12  of dialyzer cartridge  10 . This may be accomplished by adding a tubing conduit  595  that provides a fluid communication pathway between the substitution filter port  348  and port  89  on the treatment module  100 A. The tubing conduit may contain a fluid restrictor  596 , or may be of sufficient length and diameter to provide a given flow resistance (i.e. pressure drop) at a given flow rate through the tubing conduit  595 . Operation of the treatment module  100 A is as follows. Initially the pinch valve  84  is closed to prevent fluid from passing through conduit  82  leading to the extracorporeal circuit. The substitution pump  62  is turned on to a rate that is equal to or greater than the dialysate flow rate entering in from the dialysis machine. This redirects all incoming dialysate fluid from conduit  120 , though conduit  64 , into the substitution pump where it is pumped into conduit  360 , across the first stage of the substitution filter  92 , through conduit  595 , and out into conduit  130  leading to the dialyzer  10 . If the substitution pump  62  is running at a faster rate than the incoming dialysate stream, a portion of filtered dialysate fluid may be recirculated back to the substitution pump  62  via conduit  120  which is in fluid communication with conduit  64 . If the flow resistance characteristics along the fluid path are known, for example the flow path that includes the first stage of the substitution filter  92  and tubing conduit  595 , it is possible to calculate the pumping rate of the substitution pump  62  using pressure readings from pressure transducers  66  and  60 . Likewise, if the substitution pump rate is known (such as if one is using a positive displacement type metering pump) one can calculate a pressure differential between transducers  66  and  60 . For example, when the pinch valve  84  is closed such that no fluid is transferred across the second stage of the substitution filter  92 , one can calculate the differential pressure as the product of the pumping rate and the fluid path flow resistance. Upon opening the pinch valve  84 , one can monitor how much the differential pressure changes at pressure transducers  66  and  60  as a means to determine the substitution fluid flow rate being delivered to the extracorporeal circuit for diafiltration. For example, if no change in differential pressure occurs when opening the pinch valve  84 , one can assume that no substitution fluid was generated and that all fluid passed through tubing conduit  595 . If a change in the differential pressure is recorded by transducers  66  and  60 , such that the differential pressure between  66  and  60  is less than before when pinch valve  84  was closed, one can assume that a portion of fluid was delivered to the extracorporeal circuit via conduit  82 . By measuring the pressure differential, ΔP, where ΔP is defined as the pressure at transducer  66  minus the pressure at transducer  60  (i.e. ΔP=P 66 −P 60 ) at a given substitution pump  62  pumping rate (designated as Q pump ), one can calculate the delivered substitution fluid rate (Q sub ) as follows:
 
 Q   sub   =Q   pump (1 −ΔP   open   /ΔP   closed )
 
     where ΔP open  is the pressure differential when pinch valve  84  is open, and
         ΔP closed  is the pressure differential when pinch valve  84  is closed.
 
Since ΔP closed  can be determined prior to treatment over a pre-set range of substitution pump speeds (Q pump ), or can be based on a theoretical calculation for a known fluid path resistance, one may then set up a feedback control loop to drive the substitution pump  62  based on inputs from pressure transducers  66  and  60  and a desired set point for Q sub . It has also been discovered by the inventors that the addition of a fluid restrictor  598 , such as located in the tubing conduit  82  between the outlet of the substitution filter and the extracorporeal circuit and preferably before the pinch valve  84 , may improve the ability to control the substitution rate. For example, it has been found that better control is achieved when flow resistances of the fluid restrictors  596  and  598  are substantially greater than say the flow resistance across the first sterilizing filter stage of the substitution filter  92 . Also, it is preferable that the combined flow resistance of the second sterilizing filter stage of the substitution filter  92  and the fluid restrictor  598  should be equal to or greater than the fluid resistance through tubing conduit  595  which may or may not contain a fluid restrictor  596 . This based on an analysis that predicted a net change of actual substitution rate (Q sub ) upon a set change of the substitution pump rate (Q pump ).
       

     Reference is now made to  FIG. 10   c  which shows the configuration illustrating connections between the treatment module  100 A, the reuse/test module  100 B, and the substitution fluid filter  92  during test and disinfection operations. First, substitution filter caps  590  have been removed in order to attach connectors  350  and  574  to the filters ports  348 , and  576  respectively. Conduit  366  provides a fluid pathway between connector  350  and the fluid reservoir  300  of the reuse/test module  100 B in a similar manner as described with reference to  FIG. 1   e . Conduit  574  is connected to a water source  572 , which is used for rinsing, priming and purging air out of the substitution filter  92  and the fluid paths of both modules  100 A and  100 B. The water source should be of suitable quality as known in the art, such as AAMI quality water used in hemodialysis and/or dialyzer reprocessing systems. A water inlet pressure regulating valve  568  and an inlet water valve  566  may be included, for example, to regulate water pressure in the two modules  100 A and  100 B. The substitution filter rinse line, now includes only a straight tubing conduit  416  with end connectors  418  and  412 . Connector  412  is connected to the outlet substitution filter port  79  while connector  418  is connected to treatment module  100 A rinse port  346 . The treatment module shunt connector containing conduit  342  is removed and fluid conduits  476  and  582  are connected to rinse ports  344  and  89  via connectors  482  and  480  respectively. Conduit  476  provides a fluid communication pathway to a reservoir  472  which contains a concentrated disinfectant solution  478 . Conduit  582  provides a fluid communication pathway to the bottom of an internal fluid reservoir  300  of the reuse/test module  100 B. Two additional conduits are present in the reuse/test module  100 B. These are conduits  562  and  570 . Conduit  562  tees into conduit  366  and thus provides a fluid communication pathway to a drain  580 . Conduit  570  provides a fluid path between conduits  574  and  562 . Test and disinfect operations are described more fully below. 
     Rinsing and/or purging air out of the substitution filter  92  and fluid path circuit (but excluding the disinfectant line  476  and air vent line  362 ) is accomplished by first opening valves  566 ,  371  and  560  (all other valves are closed) to allow water to flow through conduit  574 , into substitution filter compartments  526  and  528 , through conduits  366  and  562 , and out to drain  580 . Next, valves  97 ,  372 , and  87  can be opened while closing valve  371 . Then by turning the substitution pump ON in the reverse direction (outlet toward conduit  64 ), flow of water will occur across the two semi-permeable membranes  521  and  523  from compartments  526  and  528  and into compartments  524  and  530 . From here, flow will proceed into conduit  360  which is in parallel with conduits  416  and  368  that lead back to the substitution pump  62 . Fluid then flows through conduit  64 , where it is split into the two parallel conduits  120  and  130  that later rejoin and flow through conduit  582  leading to the fluid reservoir  300 . Any air in the fluid reservoir  300  is purged out of the top and through conduit  562  going out to drain  580 . Rinsing and purging conduit  570  is accomplished by opening valves  566  and  564  (all others being closed) to shunt water from the higher pressure water inlet side to the lower pressure drain side. 
     A fluid path integrity test to verify that the fluid path and connections to the substitution filter are intact can be performed in a manner very similar to that described earlier with reference to  FIG. 1   e . For example, one can close all valves except valves  97 ,  371  and  372  and turn ON the substitution pump  62  in the forward direction for a period of time or until a certain pressure is observed at the discharge pressure transducer  66 . Here, a positive pressure generally develops in the substitution filter cartridge  92  while a negative pressure is generated in the fluid reservoir  300 . At the end of the pressurizing period, the substitution pump  62  may be turned OFF and, after a specified stabilization period, the control unit  110  may monitor the rate of pressure decay over a set test period. Any fluid path leaks may then be detected when the measured pressure decay exceeds a predetermined limit. Similarly, a second integrity test may be performed with the substitution pump  62  operated in the reverse direction. Here, a positive pressure generally develops in the fluid reservoir  300 , while a negative pressure is generated in the substitution filter cartridge  92 . 
     Next, a water permeability test may be performed as a means to monitor the degree of plugging of the first filter stage  520  of the substitution fluid filter  92 . This may be accomplished by running the substitution pump  62  in the forward direction at a specified rate with all valves closed except for valves  87 ,  371  and  372 . Fluid then runs from the substitution pump  62 , through conduit  360  and across the first stage  520  of the substitution filter which includes the semi-permeable membrane  521 . Next it passes through conduit  366 , into reservoir  300 , and out through conduit  582  which feeds into conduit  120 . It is then returned to the substitution pump  62  via conduit  64 . By monitoring pressures at pressure transducers  60  and  66 , one may determine the degree of plugging by comparing the resulting pressure differential relative to that of a new substitution filter. 
     A substitution filter membrane integrity test that tests both filter stages  520  and  522  simultaneously may also be performed as follows. First, the fluid reservoir  300  must be partially emptied. This may be accomplished by opening valves  99 ,  371  and  560  (all other valves closed) and turning ON the substitution pump  62  in the forward direction. As fluid is drawn out of the fluid reservoir  300  by action of the substitution pump, air will enter the fluid reservoir  300  through the vented conduit  362 . Fluid removed from the reservoir will then flow out through conduit  582 , into conduit  120 , and sequentially through conduit  64 , conduit  360 , compartment  524 , compartment  526 , conduit  366 , and conduit  562  where it goes out to drain  580 . Next, valves  87 ,  371  and  97  are opened, valve  560  is closed, and the substitution pump  62  turned ON in a reverse direction. Now a negative pressure is simultaneously generated at the inlet and outlet ports,  77  and  79 , of the substitution filter  92 . This will in turn draw fluid across both filter membranes  521  and  523  such that fluid flows from the first downstream compartment  526  into the first upstream compartment  524  and from the second upstream compartment  528  into the second downstream compartment  530 . Because the first downstream compartment  526  and the second upstream compartment  528  is fluid communication with the top of the fluid reservoir  300  via conduit  366 , air in the top of the partially full fluid reservoir  300  will flow into conduit  366  and eventually into the filter compartments  526  and  528 . When the fluid in compartments  526  and  528  is completely displaced by the air, the negative pressure as sensed by pressure transducer  66  should become more negative since air should not be able to cross the semi-permeable membranes  521  and  523 , assuming they are intact. Upon reaching a specified negative pressure, the substitution pump  62  may be turned OFF provided it is an occluding type pump. After a specified stabilization period, the control unit  110  may monitor the rate of pressure decay over a set test period. Any substitution filter integrity leaks may then be detected when the measured pressure decay exceeds a predetermined limit as is known in the art as a pressure decay test. Upon passing the pressure decay test, refilling the substitution filter compartments  526  and  528  with fluid may be accomplished in a similar manner described above for rinsing and/or purging air out of the substitution filter and fluid path. 
     With continued reference to  FIG. 10   c , fluid path of modules  100 A and  100 B and the substitution filter  92  may be loaded with a disinfectant solution for disinfection of the fluid path and substitution filter. For a chemical disinfection, a concentrated disinfecting solution  478  may be placed into the fluid reservoir  472 . This fluid may be drawn into the fluid path by opening valves  95 ,  97 ,  87  and  560  (all other valves closed), and turning on the substitution pump  62  in the reverse direction with flow leading into conduit  64 . 
     Provided the substitution pump  62  is an occluding type pump, such as a metering pump, a specified volume of concentrated disinfecting solution  478  can be pumped into the fluid path as necessary to achieve a desired final concentration upon mixing with water already contained in the fluid path. In addition, it is possible as part of this step or a previous step to purge air out of the fluid reservoir  300  prior to the starting the next step. Mixing may be accomplished by opening valves  87 ,  371  and  97  (all other valves closed) and turning the pump ON in the reverse direction. This forms a recirculating loop that pumps fluid through the circuit as follows. From the substitution pump  62 , fluid is pumped into conduit  64  and into parallel conduits  120  and  130 . Next it rejoins and passes through conduit  582  and into the fluid reservoir  300 . Fluid in the reservoir is pushed out the top and into conduit  366  that leads to the substitution fluid filter compartments  526  and  528 . This fluid is then simultaneously pushed across the semi-permeable membranes  521  and  523  and into compartments  524  and  530 . Fluid from compartment  524  flows into conduit  360  while fluid in compartment  530  flows into conduit  416  that leads to conduit  368 . Here it is rejoined with the fluid in conduit  360  that leads back to the substitution pump  62 . After a period of time, the fluid in this recirculating loop will become mixed thus having a uniform concentration throughout. To complete exposing the fluid path to the disinfecting solution, valves  99  and  564  are opened (all others closed) with the substitution fluid pump  62  turned ON in the forward direction. Due to the pumping action, air will enter the fluid reservoir  300  through conduit  362  as the disinfectant solution is drawn toward the substitution pump  62  via conduits  582 ,  120 , and  64 . The pump will then push the fluid into compartments  524  and  530 , across the semi-permeable membranes  521  and  523 , into compartments  526  and  528 , out through conduit  574 , where it passes through conduit  570 , and out to drain  580 . Upon completion, the substitution filter may be removed from the treatment and test modules  100 A and  100 B for storage, such as may be necessary to satisfy a minimum disinfectant dwell period. In removing the substitution filter  92 , connectors  150  and  418  are detached from ports  77  and  346  and reconnected such that  150  connects to port  346  and  418  connects to port  77  (not shown). Connectors  350  and  574  are detached from the substitution filter and are placed on rinse ports  578 . Caps, such as indicated by  590  in  FIG. 10   a , can then be placed on reuse test module  100 B dual rinse ports  578  to contain the fluid in the substitution fluid filter  92 . 
     It will be appreciated by persons skilled in the art to which this invention pertains that the invention is not limited to the preferred embodiments and configurations described above and with reference to the accompanying drawings.