Abstract:
A disposable cartridge for use in a hemodialysis machine has a blood flowpath for carrying a volume of blood to be treated in a dialyseer and a dialysate flowpath, isolated from the blood flowpath, for delivering a flow of dislysate solution through the dialyser. The cartridge is received in an engine section of the machine. The engine section has first and second platens which close when the cartridge is inserted to retain the cartridge. Actuators and sensors arranged on the second platen control operation of the cartridge.

Description:
[0001]    This application is a continuation of U.S. application Ser. No. 11/919,694, filed Oct. 31, 2007, which in turn is a U.S. national stage application of International Application No. PCT/GB2006/001668 with an International filing date of May 8, 2006 and a priority date of May 6, 2005. 
     
    
     FIELD OF THE INVENTION 
       [0002]    The present invention relates to dialysis machines and in particular, but not exclusively, to a disposable cartridge for use in hemodialysis machine. 
       BACKGROUND OF THE INVENTION 
       [0003]    Dialysis is a treatment which replaces the renal function of removing excess fluid and waste products, such as potassium and urea, from blood. The treatment is either employed when renal function has deteriorated to an extent that uremic syndrome becomes a threat to the body&#39;s physiology (acute renal failure) or, when a longstanding renal condition impairs the performance of the kidneys (chronic renal failure). 
         [0004]    There are two major types of dialysis, namely hemodialysis and peritoneal dialysis. 
         [0005]    In peritoneal dialysis treatment, a dialysate solution is run through a tube into the peritoneal cavity. The fluid is left in the cavity for a period of time in order to absorb the waste products, and is subsequently removed through the tube for disposal. 
         [0006]    It is common for patients in the early stages of treatment for a longstanding renal condition to be treated by peritoneal dialysis before progressing to hemodialysis at a later stage. 
         [0007]    In hemodialysis, the patient&#39;s blood is removed from the body by an arterial line, is treated by the dialysis machine, and is then returned to the body by a venous line. The machine passes the blood through a dialyser containing tubes formed from a semipermeable membrane. On the exterior of the: semipermeable membrane is a dialysate solution. The semipermeable membrane filters the waste products and excess fluid from the blood into the dialysate solution. The membrane allows the waste and a controlled volume of fluid to permeate into the dialysate whilst preventing the loss of larger more desirable molecules, like blood cells and certain proteins and polypeptides. 
         [0008]    The action of dialysis across the membrane is achieved primarily by a combination of diffusion (the migration of molecules by random motion from a region of higher concentration to a region of lower concentration), and convection (solute movement that results from bulk movement of solvent,’ usually in response to differences in hydrostatic pressure). 
         [0009]    Fluid removal (otherwise known as ultrafiltration) is achieved by altering the hydrostatic pressure of the dialysate side of the membrane, causing free water to move across the membrane along the pressure gradient. 
         [0010]    The correction of uremic acidosis of the blood is achieved by use of a bicarbonate buffer. The bicarbonate buffer also allows the correction of the blood bicarbonate level. 
         [0011]    The dialysis solution consists of a sterilized solution of mineral ions. These ions are contained within an acid buffer which is mixed with the serilised water and bicarbonate base prior to delivery to the dialyser. 
         [0012]    Dialysate composition is critical to successful dialysis treatment since the level of dialytic exchange across the membrane, and thus the possibility to restore adequate body electrolytic concentrations and acid-base equilibrium, depends on the composition. 
         [0013]    The correct composition is accomplished primarily by formulating a dialysate whose constituent concentrations are set to approximate normal values in the body. 
         [0014]    However, achieving the correct composition of dialysate requires the accurate control of low volumes of liquid and at present this is achieved by the provision of complex fluid paths, including multiple pumping and valving components on the dialysis machine. 
         [0015]    This presents the disadvantage of a complex and costly dialysis machine which is at increased risk of failure by virtue of its complexity. Increased maintenance is also a problem since it is essential to minimize machine downtime in order to most efficiently treat the patient. 
         [0016]    A further problem with known hemodialysis machines is that the blood and dialysate solution lines require careful mounting onto the dialysis machine before the treatment can commence. This presents a risk that the lines are not correctly installed, a risk which is particularly relevant to those patients who dialyse at home. 
         [0017]    This method of dialysis also presents an increased risk of cross-infection between patients since the disposable blood and dialysate lines come into contact with the dialysis machine. 
       OBJECT OF THE INVENTION 
       [0018]    It is an object of the present invention to provide a hemodialysis system which at least mitigates some of the problems described above. 
       SUMMARY OF THE INVENTION 
       [0019]    According to a first aspect of the invention there is provided a disposable cartridge for use in a hemodialysis machine, the cartridge comprising a blood flowpath for carrying a recirculating volume of blood to be treated in a dialyser and a dialysate flowpath, isolated from the blood flowpath, for delivering a flow of dialysate solution through the dialyser. 
         [0020]    Preferably, the cartridge has a first mixing pump and a second mixing pump, the second mixing pump accepting a homogoneous mix of sterile water and a first dialysate solution base from the first mixing pump and introducing a further dialysate solution base. 
         [0021]    Preferably, the dialysate pathway includes a first three-way valve upstream of the first dialysate solution mixing pump, the first three-way valve controlling delivery of the first dialysate solution base into the first mixing pump. 
         [0022]    Preferably, the first three-way valve has a mixing pump outlet port, a dialysate solution reservoir inlet port and a positive displacement pump port. 
         [0023]    Preferably, the first three-way valve acts to permit a volume of a first dialysate solution base into the first dialysate solution mixing pump on each and every stroke of the pump. 
         [0024]    Preferably, the dialysate pathway includes a second three-way valve upstream of the second dialysate solution mixing pump. 
         [0025]    Preferably, the cartridge includes a dialysate solution reservoir, more preferably a first reservoir immediately downstream of the first mixing pump and a second reservoir immediately downstream of the second mixing pump. 
         [0026]    Preferably, the blood and dialysate fluid pathways pass between a first outwardly facing surface of the cartridge and a second outwardly facing surface of the cartridge. 
         [0027]    Preferably, at least some parts of the first and second outwardly facing surfaces of the cartridge body are covered with a deformable membrane. 
         [0028]    Preferably, the valves and pumps on the cartridge are actuable by deformation of the membrane by the dialysis machine. 
         [0029]    Preferably, the blood and dialysate solution fluid pathways are at least partially defined by upwardly standing walls projecting outwardly from the upper and lower surfaces of the cartridge. 
         [0030]    Preferably, the upstanding walls are enclosed by the deformable membranes. 
         [0031]    Preferably, the mixing pumps are membrane pumps. 
         [0032]    Preferably, the blood flow path is provided with at least one blood bubble trap, more preferably, the or each blood bubble trap is provided with a level sensor. 
         [0033]    Preferably, the level sensor is an optical level sensor, or an ultrasonic level sensor. 
         [0034]    Preferably, the blood bubble trap is provided with an upper and a lower level sensor. 
         [0035]    Preferably, the blood bubble trap is provided with a hydrophilic membrane for removing or adding a volume of air to the blood bubble trap. 
         [0036]    Preferably, the cartridge is provided with a positive displacement pump plunger acting in combination with the three-way valve to deliver a measured volume of dialysate solution base into the dialysate solution mixing pumps. 
         [0037]    Preferably, the cartridge is provided with an endotoxin filter, preferably a single use endotoxin filter. 
         [0038]    Preferably, the dialysate solution fluid pathway is provided with an ultra-sonic flow sensor for detecting the flow rate through the dialysate solution path. 
         [0039]    Preferably, the cartridge defines a series of apertures interlinking the portion of fluid pathways defined on the upper surface of the cartridge with the portion of fluid pathways defined on the lower surface of the cartridge. 
         [0040]    According to a second aspect of the invention there is provided adialysis machine adapted to receive the dialysis cartridge of the first aspect of the invention, the machine including at least one platen arranged in use to hold the cartridge in position on the machine. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0041]    The invention will now be described, by way of example only, and with reference to the following drawings, in which: 
           [0042]      FIG. 1  is an isometric view of the dialysis machine and cartridge of the current invention, 
           [0043]      FIG. 2  is an isometric view of the engine portion of the machine of  FIG. 1 , 
           [0044]      FIG. 3  is an isometric view of the cartridge of the present invention, 
           [0045]      FIG. 4  is a front view of the cartridge of  FIG. 3 , 
           [0046]      FIG. 5  is a front view of the pumping portion of the cartridge of  FIG. 3  showing partial hidden detail, 
           [0047]      FIG. 6  is a front view of the cartridge of  FIG. 3  showing the dialyser cover removed, 
           [0048]      FIG. 7  is a rear view of the pumping portion of the cartridge of  FIG. 3 , 
           [0049]      FIG. 8  is a top view of the cartridge of  FIG. 3 , 
           [0050]      FIG. 9  is an end view of the cartridge of  FIG. 3 , and 
           [0051]      FIG. 10  is a schematic representation of a dialysate solution base delivery system according to the present invention. 
       
    
    
     DETAILED DESCRIPTION 
       [0052]    In  FIG. 1  a dialysis machine  1  is shown having a cover  2  which opens to reveal a storage compartment  3 . The machine has an engine section  4  which receives a dialysis cartridge  10 . 
         [0053]    Referring now to  FIG. 2 , the engine section  4  is shown in further detail to include first and second platens  5 ,  6  which dose upon insertion of the cartridge  10  into the machine to retain the cartridge in position in use. The engine  4  has pneumatic actuators  7  and sensors (indicated generally at  8  in  FIG. 2 ) arranged on the second platen to control operation of the cartridge  10  as will be described in further detail shortly. 
         [0054]    In  FIGS. 3 and 4  a dialysis cartridge  10  is shown having a pumping portion  12  (to the right of dashed line I- 1  in  FIG. 4 ) and a dialysis portion  14  (to the left of dashed line I-I in  FIG. 4 ). The pumping portion  12  has the form of a fiat rectangle. The dialysis portion  14  has a dialyser cover  15  which is shaped so as to contain a dialyser as will be described in further detail shortly. 
         [0055]    Referring briefly to  FIG. 8 , the pumping portion  12  of the dialysis cartridge  10  has an upper surface  16  and a lower surface  18 . The upper surface  16  and a lower surface  18  are covered by a dear membrane  20 ,  22 , respectively, which is formed from a deformable plastics material. The first and second membrane,  20 ,  22  are bonded to the upper surface  16  and a lower surface  18 , respectively by way of adhesive or similar known method. 
         [0056]    Referring now to  FIG. 4 , the upper surface  16  defines a series of upstanding walls indicated, for example, as  24 . The upstanding walls  24  define a system of flow channels as will be described in further detail shortly. The channels are enclosed at the outermost part of the upper surface  16 , by the first membrane  20 . Accordingly, the upper surface  16  defines a series of fluid channels for carrying either the blood to be dialysed, or the Dialysate solution. 
         [0057]    The cartridge  10  also defines the series of apertures, indicated generally for example at  26  in  FIG. 4 . These apertures provide a fluid pathway through the cartridge  10 , the purpose of which will now be described. 
         [0058]    Referring to  FIG. 7 , the lower surface  18  also defines a series of upstanding walls  24 , which collectively define a labyrinth of fluid channels enclosed by the second membrane  22 . 
         [0059]    In combination therefore the upper surface  16 , lower surface  18  and the first and second membranes  20 ,  22  form a series of interconnected fluid flow paths on both sides of the pumping portion  12 . This labyrinth of fluid flowing pathways will now be described in further detail. 
         [0060]    The first membrane  20  is bonded to the upper surface  16 , and similarly the second membrane  22  bonded to the lower surface  18 , so as to contain the fluids within their respective channels. 
         [0061]    The dialyser cartridge  10  defines two primary fluid pathways, firstly, a flow path for blood and secondly a flow path for the dialysate solution. The blood pathway is formed as follows. 
         [0062]    The patient&#39;s blood enters the dialysis cartridge  10  via an arterial port  28 . The blood then passes from the upper surface  16  to the lower surface  18  via an arterial port aperture  30  where it is then carried by an arterial port channel  32  from the arterial aperture  30  to an arterial blood bubble trap  34 . The arterial blood bubble trap  34  has an inlet lip  36  for directing the incoming blood towards the bottom of the trap. Arranged at the bottom of the trap is a blood bubble trap exit  38  which carries the blood from the arterial blood bubble trap  34  to an arterial blood bubble trap aperture  40  via channel  42 . 
         [0063]    The purpose of the arterial blood bubble trap  34  is to remove from the arterial blood supply any gas bubbles which may be contained therein. Gas bubbles may impair the performance of dialyser, and furthermore, present a risk to the patient if they were reintroduced back into the body via the venous blood line. The blood bubble trap  34  is also provided with an upper level sensor port  44  and a lower level sensor port  46 . The level sensor ports  44 ,  46  are arranged to coincide with corresponding optical level sensors arranged on the dialysis machine. Accordingly, the level sensors are able to optically interrogate the arterial blood bubble trap  34  so as to ensure that the level in the blood bubble trap is above the level of the lower level sensor port  46  and below the level of the upper level sensor port  44 . It is important to ensure that the blood level remains between these two levels so that there always remains a volume of air in the blood level trap into which any gas bubbles carried in the blood can migrate. 
         [0064]    Having passed through the arterial blood bubble trap aperture  40  the blood is carried on the upper surface  16  to a blood pump inlet valve  48  (see  FIG. 4 ). 
         [0065]    Referring to  FIG. 4 , the blood pump inlet valve  48  is operable between a closed condition and an open condition as follows. The valve  48  has an outer annular upstanding wall  50  and an inner annular upstanding wall  52 . Arranged inwardly of the inner upstanding annular wall  52  is a valve aperture  54 . The inner upstanding annular wall  52  is recessed from the outer upstanding annual wall  50  in a direction towards the cartridge  10 . Arranged between the inner and outer upstanding annual wall  50 ,  52  is a sector aperture  56  which acts as an outlet from the valve  48 . Accordingly, the valve  48  has a valve inlet in the form of valve aperture  54  and an outlet in the form of the sector aperture  56 . As discussed previously, the lower surface  18  has its outer service covered by a deformable membrane  22 . The deformable membrane  22  rests against the outwardly facing surface of the outer upstanding annular wall  50  where the valve is in the un-actuated, open state. In order to change the condition of the valve  48  from the open state to the closed state, the dialysis machine applies a positive pressure to the exterior surface of the second membrane  22  in order to drive the inner surface of the membrane on to the outwardly facing surface of the inner upstanding annular wall  50 . This doses the inlet to the valve thereby preventing flow through the valve. 
         [0066]    With the blood pump inlet valve  48  in the open state, the blood flows through the arterial blood bubble trap aperture  40  over the inner upwardly standing wall  50  and through the sector aperture  56  so as to exit the blood pump inlet valve  48 . From the sector aperture  56  the blood then flows down a blood pump inlet channel  58  and into a blood pump  60  via a blood pump inlet  62 . 
         [0067]    The blood pump is defined by a dome shaped pump cavity  64  into which the blood pump inlet  62  opens. Arranged at the centre of the pump chamber  64  is a pump outlet  66 . The outer edge of the pump chamber  64  is defiled by an annular upstanding wall  68 , the outwardly facing surface of which is in contact with the inner surface of the second membrane  22 . A volume of blood is drawn into the pump chamber  64 , through the open blood pump inlet valve  48  as follows. 
         [0068]    The dialysis machine generates a negative pressure on the outside surface of the second membrane  22  in order to deform the membrane outwardly away from the lower surface  18 . With the pump chamber  64  full, and the pump at full stroke, the blood pump inlet valve  48  is closed by the dialysis machine generating positive pressure on the outside surface of the second membrane  22  in order to dose the valve aperture  54 . The pump chamber  64  is then evacuated by the dialysis machine applying a positive pressure to the outside surface of the second membrane  22  in order to drive the blood contained within the pump chamber  64  through the pump outlet  66 . The pump outlet  66  is in fluid communication with a blood pump outlet valve  70  which is identical in form to the blood pump inlet valve  48 . It follows that with the blood pump inlet valve closed, and the blood pump  60  being driven by the dialysis machine to evacuate the pump  64 , the blood pump outlet valve  70  is in an open state in order to permit the flow of blood past the valve  70  and through a blood pump outlet valve aperture  72 . 
         [0069]    Accordingly, the blood pump  60  is in combination with the blood pump inlet valve  48  and the blood pump outlet valve  70 . Specifically, the blood pump inlet valve  48  opens when the blood pump is in the expansion stroke in order to admit blood into the pump chamber, whilst the blood pump outlet valve  70  remains closed in order to prevent back-flow of blood through the system. The inlet valve  48  then closes at the same time as the outlet valve  70  is opened in order to allow the compression stroke of the flow pump to drive the blood from the pump chamber  64  and through the blood pump outlet valve aperture  72 . 
         [0070]    From the aperture  72 , the blood then flows through a pressure sensor chamber  74 . As the blood flows through the chamber  74 , the fluid pressure causes a force to be applied to the first membrane  20  which in turn causes a deflection in the membrane. This deflection is detected by a sensor provided in the dialysis machine and this measured deflection is calibrated to generate a blood pressure reading for within the cartridge. 
         [0071]    From the pressure sensor chamber  74  the blood then passes through a dialyser blood port  76 . 
         [0072]    Referring now to  FIG. 6 , the blood flows from the dialyser blood port  66  down a dialyser blood line  78  and into the bottom end of a dialyser  80  of known design. The dialyser  80  contains multiple axially extending semi-permeable tubes through which the blood passes. Upon exiting the dialyser  80  the blood travels down a dialyser return blood line  82  before passing into a venous blood bubble trap  86  via a dialyser blood return Port  84 . 
         [0073]    The venous blood bubble trap  86  is similar in design to the arterial blood bubble trap  34  in that it has an inlet lip  88 , an optical level sensor  90  and a hydrophilic membrane  94  to allow the hydrolysis machine withdraw or administer a volume of air to or from the bubble trap in order to maintain a constant blood level within the bubble trap. The venous blood level trap  86  is further provided with an ultrasonic level sensor  92  the design of which will be described in further detail shortly. At the bottom end of the valve trap is a thrombus filter  96  for trapping blood dots within the bubble trap. The Thrombus filter may be of conical form as in known thrombus filters or may be wedge shaped. Having passed through the thrombus filter  96 , the blood passes through an ultrasonic flow rate sensor  98  which will be described in further detail shortly. The blood is then returned to the patient via a venous port  100 . 
         [0074]    The blood therefore completes its passage through the dialysis cartridge  10  from the arterial port  28  through the arterial blood bubble trap  34 , the blood pump inlet valve  48  and into the blood pump  60 . From blood pump  60  the blood is driven past the blood pump outlet valve  70  and into the dialyser  80  via the cross membrane pressure sensor  74 . Upon exit from the dialyser  80 , the blood is returned to the dialysis cartridge  10  via the dialyser blood return port  84 . Upon exit from the port  84  the blood enters the venous blood bubble trap  86 , passes through the thrombus filter  96  and flow sensor  98  before being returned to the patient via the venous port  100 . 
         [0075]    A syringe  71  is provided which introduces a volume of an anti-coagulant drug such as heparin into the blood line between the blood pump outlet valve  70  and the dialyser  80 . The syringe plunger  73  is driven by the machine engine as shown in  FIG. 2 . 
         [0076]    As described above, dialysis occurs across a semi-permeable membrane, in this instance the semi-permeable tubes provided within the dialyser  80 . As described, the blood flows through the centre of the semi-permeable tubes and it therefore follow that the dialysate solution flows in the space within the dialyser  80  between the tubes. The mixing of the dialysate solution on the cartridge at the correct concentration will now be described in detail. 
         [0077]    The pump portion  12  defines the dialysate flow path in addition to the blood flow path as described above. 
         [0078]    Accordingly, the dialysis cartridge  10  provides for the mixing into a sterile water supply of a small volume of concentrated bicarbonate solution and a small volume of acid solution. The resulting dialysate solution is pumped from the pumping portion to deliver the solution to the dialyser. The cartridge further allows for the accurate sensing of dialysate solution concentration, dialysate flow rate and dialysate pressure. 
         [0079]    Sterile water enters the dialysis cartridge  10  via a sterile water inlet  102 . The sterile water is then mixed with a controlled volume of bicarbonate solution base as follows. The cartridge  10  defines a chamber  104 , for receiving the plunger of a positive displacement pump (not shown for clarity in  FIGS. 3 to 9 ). The pump acts in combination with a three-way valve  106  of known design. The pump and three-way valve  106  are operated by the dialysis machine to micro-dose a controlled volume of bicarbonate solution into a bicarbonate pump  108 . The bicarbonate pump  108  is of similar design to the blood pump  60  with the exception that the bicarbonate pump  108  is additionally provided with an inlet  110  from the three-way valve  106 . The bicarbonate pump  108  is controlled in exactly the same manner to the flow pump  60  in order to draw a volume of sterile water through the sterile port at  102  and past a bicarbonate inlet pump  112  whilst a bicarbonate pump outlet valve  114  remains closed. At the same time as a volume of sterile water is drawn into the pump a small volume of saturated bicarbonate solution is injected into the bicarbonate pump  108  by a positive displacement pump. The body of the positive displacement pump is defined by the cartridge body. The saturated bicarbonate solution is drawn from a reservoir on the dialysis machine. The solution is delivered to the pump via a bicarbonate inlet channel  105  and three-way valve  106 . 
         [0080]    The action of drawing the water into the pump chamber by means of applying a negative pressure to the outer surface of the first membrane  20  generates a turbulent flow within the pump chamber which causes the sterile water and bicarbonate solution to be mixed thoroughly within the pump chamber. Accordingly, at the point where the bicarbonate pump inlet valve  112  is closed, and the outlet valve  114  opens in order to drive a solution from the pump chamber, a thorough homogoneous mixing has been achieved. 
         [0081]    The bicarbonate and water solution is pumped out of the pump chamber via a pump exit  116  from which it flows past the pump outlet valve  114  and into a water-bicarbonate solution reservoir  118 . The volume of the water-bicarbonate reservoir  118  is approximately four times the volume of the bicarbonate pump chamber and performs two functions. Firstly, it further ensures that the mixture is homogenous, and secondly acts as a fluid buffer within the dialysate solution flow path, the purpose of which will be described in further detail shortly. 
         [0082]    The bicarbonate solution reservoir  118  is provided with a conductivity sensing probe  120  and a temperature sensing probe  122 , an upper level sensor  124  and a lower level sensor  126 . 
         [0083]    The conductivity and temperature sensor probes are provided to contact with conductivity and temperature sensors in the dialysis machine. The measurements are used to deduce the concentration of the water-bicarbonate solution in the reservoir  118 . The resevoir also acts as buffer to allow for the various system pumps being out of phase. Accordingly, the level in the resevoir is able to rise and fall thereby averaging out pressure spikes in the system. 
         [0084]    From the water-bicarbonate resevoir  118 , the solution is drawn into an acid pump  128  past an open acid pump inlet valve  130 . Coupled to the acid pump  128  is an acid pump outlet valve  132 . The purpose of the acid pump  128  is to introduce a small volume of acid solution base into the water-bicarbonate solution. This process is achieved using the same valuing and pumping methodology as employed for the bicarbonate pump  108 . Specifically, a second chamber  107  is provided for receiving the plunger of a second positive displacement pump. A volume of acid solution base is thereby dispensed down a acid inlet channel  109  to a second 3-way valve  111 . Under the action of the pump  128 , water-bicarbonate solution is drawn into the pump chamber. The the acid solution base is injected into the pump by a second positive displacement pump. The fluids are thoroughly mixed in the turbulent flow within the pump chamber before being dispensed passed the outlet valve  132  into a water-bicarbonate-acid reservoir  138 . 
         [0085]    The water-bicarbonate-acid reservoir  138  is provided with a conductivity sensing probe  144  and a temperature sensing probe  146 , an upper level sensor  140  and a lower level sensor  142 , in common with the water-bicarbonate reservoir  118 . 
         [0086]    From the water-bicarbonate-acid reservoir  138 , the solution flows through a resevoir exit  147  (see  FIG. 7 ) into a flow balance inlet channel  148 . The solution is thereby delivered to the flow balancer  150 . 
         [0087]    The purpose of the flow balancer  150  is to ensure that the volume of dialysate solution pumped into the dialyser is the same as that withdrawn from the dialyser  80 . The purpose of matching the flow into and out of the dialyser is to match the osmotic potential of the dialysate solution within the dialyser to the osmotic potential of the blood. This ensures that the volume of the fluid removed from the blood, or transferred to the blood, can be carefully controlled. This is critical to ensuring that the patient is not hydrated or dehydrated to a dangerous extent during the dialysis treatment. 
         [0088]    The flow balancer  150  is provided with a first flow balance pump  152  and a second flow balance pump  154 . The first and second flow balance pumps  152 , 154  have a similar mode of operation to the blood pump  60 , and the mixing pumps  108 ,  128 . However, the flow path for delivering fluid to each of the flow balance pumps  152 ,  154  is rather more complex due to the way in which the flow balancer  150  achieves the controlled fluid flow input and output from the dialyser  80 . 
         [0089]    In principal, the flow balancer  150  operates by using the first flow balance pump  152  to pump dialysate solution into the dialyser, and the second flow balance pump  154  to withdraw the dialysate solution from the dialyser, for a period of time, before switching the second flow balance pump  154  to pump dialysate solution into the dialyser, and the first flow balance pump  152  withdrawing dialysate solution from the dialyser. The purpose of this mode of operation is to eliminate the effect of manufacturing tolerances in generating a mismatch in the volume of the pump chamber in each of the flow balance pumps  152 ,  154 . For example, were the first flow balance pump  152  used permanently to pump dialysate solution into the dialyser, and the second flow balance pump  154  used to withdraw dialysate solution from the dialyser, then over a period of time even the very small discrepency in the pump chamber volume of the pumps would lead to a dangerous imbalance in the volume of dialysate solution being pumped into, and withdrawn from, the dialyser. 
         [0090]    By switching the first and second flow balance pumps  152 , 154 , any errors in the chamber volume are averaged over time, thereby ensuring a balance in the flow across the dialyser. 
         [0091]    In selective fluid communication with the first flow balance pump  152  are a first flow balance pump first inlet valve  156 , a first flow balance pump second inlet valve  158 , a first flow balance pump first outlet valve  160  and a first flow balance pump second outlet valve  162 . Similarly, in selectable fluid communication with the second flow balance pump  154  are a second flow balance pump first inlet valve  164 , a second flow balance pump second inlet valve  166 , a second flow balance pump first outlet valve  168  and a second flow balance pump second outlet valve  170 . 
         [0092]    The first mode of operation of the flow balancer  150  will now be described in detail. In the first mode of operation, the first flow balance pump first inlet valve  156 , first flow balance pump second outlet valve  162 , second flow balance pump second inlet valve  166  and second flow balance pump first outlet valve  168  are all held in the closed position by the dialysis machine applying a positive pressure to the outside surface of the first membrane  20  in the region of each of the valves. Accordingly, the first mode of operation the second flow balance pump  154  is operated to pump dialysate solution into the dialyser, and the first flow balance pump  152  is operated to withdraw dialysate solution from the dialyser. 
         [0093]    With the first flow balance pump first inlet valve  156  in the closed position, dialysate solution passing out of the bicarbonate acid reservoir  138  flows past the first flow balance pump first inlet valve  156  along a flow balance inlet channel  148 . The dialysate solution then passes from the lower surface  18  to upper surface  16  via an aperture  172 . With the second flow balance pump first inlet valve  164  in its open position, the second flow balance pump  154  is able to draw a volume of dialysate solution into the pump chamber under the action of the dialysis machine generating a negative pressure on the outward facing surface of the first membrane  20 . 
         [0094]    As soon as the second flow balance pump  154  is at full capacity, the second flow balance pump first inlet valve  164  is closed, and the second flow balance pump second outlet valve  170  is opened. The pump  154  is then actuated to discharge the dialysate solution through an aperture  174  and the dialysate solution then flows along channel  176  as shown in  FIG. 10 . The dialysate solution then passes through an endotoxin filter  178  before passing through a dialyser output port  180  via channel  182 . 
         [0095]    Referring now to  FIG. 6 , from the dialysate outlet port  180 , dialysate solution passes along a dialysate inlet pipe  180  before passing along the dialyser  80  from top to bottom as shown in  FIG. 9 . In order to return the dialysate solution from the dialyser  80  to the pumping portion  12 , a dialysate outlet pipe  184  carries dialysate solution to a dialysate inlet port  186 . Upon return to the pumping portion  12 , the dialysate solution passes through a colour sensor portion  188  in order to allow a colour sensor arranged on the dialysis machine to interrogate the dialysate solution to detect for blood leakage into the dialysate solution within the dialyser  80 . On exit from the colour sensor portion  188 , the dialysate solution passes through aperture  190  and from there into a flow balance return channel  192 . 
         [0096]    Since the second flow balance pump second inlet valve  166  is closed, the dialysate solution flows past aperture  194  towards the first flow balance pump second inlet valve  158 . With the valve  158  in the open position, the first flow balance pump  152  is able to draw in to the pump chamber a volume of dialysate solution through the inlet valve  158  under the action of a positive pressure generating by the dialysis machine on the outwardly facing surface of the-first membrane  20 . The first flow balance pump second inlet valve  158  then doses, the first flow balance pump first outlet valve  160  opens, and the pump  152  drives the dialysate solution from the fluid chamber through the outlet valve  160 . The outlet valve  160  is then closed, the inlet valve  158  opened and the pump  152  driven to draw in a further volume of dialysate solution ready for dispensing in the next pump cycle. 
         [0097]    Having been delivered past the outlet valve  160 , the dialysate solution flows through aperture  196  since the second flow balance pump first outlet valve  168  is closed during the mode of operation. The dialysate solution then passes through an ultrasonic flow sensor  198  which will be described in further detail shortly, before exiting the dialysis cartridge  10  by way of dialysate solution drain  200 . 
         [0098]    In the second mode of operation, the roles of the first and second flow balance pumps  152 ,  154  are reversed. In other words, the first flow balance pump second inlet valve  158  and first flow balance pump first outlet valve  160  are held closed whilst the first inlet valve  156  and second outlet valve  162  are operated to control the flow of Dialysate solution into and out for the valve chamber. Similarly, with reference to the second flow balance pump  154 , the second flow balance pump first inlet valve  164  and second flow balance pump second outlet valve  170  are held in a closed position whilst the second flow balance pump second inlet valve  166  and second flow balance pump and first outlet valve  168  are operated to control the flow of the acid solution into and out of the pump chamber. 
         [0099]    The technique of flow balancing, as described above, is provided to ensure that exactly the same volume of dialysate solution is pumped into the dialyser  80  as is removed from it. However, in certain dialysis treatments there is a requirement to either remove excess fluid from the blood, or to transfer fluid back into the blood. This is achieved by the process of ultra-filtration in which the flow balance circuit is placed slightly out of balance by either introducing or removing a small volume of liquid to or from the diayslate solution. In the dialysis cartridge of the present invention this is achieved by an ultra-filtration three-way valve  206  which acts in combination with a positive displacement pump received in chamber  208  on the cartridge. This combination of three-way valve and positive displacement pump is identical to that used to introduce the bicarbonate solution into the bicarbonate pump  108 . The positive displacement pump plunger is received within the chamber  208  and is positioned by a drive, for example a stepper motor, on the dialysis machine. 
         [0100]    The cartridge  10  has a drainage channel  202  for draining excess fluid from the water-bicarbonate reservoir  118  and the water-bicarbonate-acid reservoir  138 . The drainage channel carries excess fluid from the reservoirs  118 ,  138  and dumps the fluid to drain via a drainage port  204  which is in fluid communication with a drainage port in the dialysis machine. 
         [0101]    Accordingly, the dialysis cartridge  10  provides two distinct flow paths, firstly for blood, and secondly for dialysate solution. The provision of an upper surface  16  and a lower surface  18 , with apertures therebetween allows the transfer of fluid from the outwardly facing surface of the upper surface to be on the facing surface of the lower surface. The blood flow path and the dialysate solution flow path are maintained discrete from one another by upstanding walls extending from the upper surface and lower surface. The outer surface of the upstanding walls abuts a deformable membrane in order to seal the flow path. 
         [0102]    It will be appreciated that the apertures provided in the first and second cartridge bodies  16 ,  18  allow for the most convenient packaging of the various cartridge features. It is dear that this feature provides a distinct advantage over cartridges which define all of the flow channels on only one side of the cartridge. 
         [0103]    In an alternative embodiment of cartridge, the arterial blood bubble trap  34  and venous blood bubble trap  86  have a collapsible element in the form of a concertina section of plastic material so as to limit the area of blood/air interface. This is particularly advantageous in that the reduced blood/air interface reduces the risk of clotting and/or separation of the blood. 
         [0104]    A further alternative feature of the bubble trap is to replace the hydrophilic membrane  94  with a membrane pump similar to the blood pump  60 . Accordingly, instead of air being added or removed to the bubble trap by way of the transfer of air across the hydrophilic membrane, the transfer of air can be achieved by the displacement of the membrane by the application of either a positive or negative pressure on the outwardly facing surface of the membrane. Furthermore, the extent of actuation of the membrane could be monitored in order to detect where an excessive volume of air is either being added to the reservoir or removed from the reservoir. 
         [0105]    In a further alternative embodiment, each of the valves, for example  48 ,  106 ,  112 ,  114 ,  164  etc are provided with rigid disks which have the diameter equal to or slightly greater than the diameter of the inner upwardly standing wall. The rigid disk is arranged between the inner upwardly standing wall and the membrane. The purpose of the rigid disc is to minimise the deformation required in the membrane in order to seal the valve. In other words, the membrane acts on the rigid disc which in turn forms a valve seat on the inner upwardly standing wall. The result of the reduced deformation of the membrane is that the transient shock waves generated in the valve by virtue of the switching between open and closed is reduced since the valve is closed at a lower peak pressure than would be necessary if the rigid disc were not present. A further benefit in addition to the reduction in pressure spiking observed in the valve body is the reduced blood damage achieved by smoother operation of the valve between its open and closed state. 
         [0106]    Referring now to  FIG. 10 , the positive displacement pump and three-way valve on the current invention are shown schematically in further detail. The three-way valve is indicated generally at  106 . It will be appreciated that the three-way valve  106  is identical to the valve in communication with the pump  128  and the ultra-filtration valve  206 . The detailed description of three-way valve  106  therefore applies equally to the other two three-way valves provided on the dialysis cartridge. 
         [0107]    The bicarbonate mixing pump  108  is connected via a fluid line to an output  250  of the three-way valve  106 . The three-way valve also has a reservoir inlet  252  and a pump inlet  254 . The reservoir inlet  252  is connected to a bicarbonate solution reservoir  255 . The reservoir  255  is provided on the dialysis machine, or attached thereto, and does not form part of the cartridge itself. The positive displacement pump is indicated generally at  258 . The positive displacement pump includes a pneumatic cylinder  260  which drives a piston arm  262  in a reciprocating manner. At the opposite end of the piston arm to the piston cylinder is a plunger  264  which acts within the cartridge chamber  104  (see  FIG. 10 ). 
         [0108]    On the return stroke indicated at A in  FIG. 10 , the plunger  264  is moved within the chamber  104  to draw in to the chamber a measured volume of dialysate solution from the bicarbonate solution reservoir  255 . This transfer of fluid is achieved by the closure of the three-way valve output  250 , with the reservoir inlet and pump inlet  252 ,  254  remaining open. The piston arm  262  is withdrawn in direction A until an abutment  268  provided on the piston arm  262  comes into contact with a moveable end stop  270 . 
         [0109]    Upon the abutment  268  hitting the moveable end stop  270 , the pneumatic cylinder  268  is driven in direction B in order to dispense the dialysate solution from the chamber  104  into the bicarbonate mixing pump  108 . This transfer of fluids is achieved by the closure of the reservoir inlet  252 , and the opening of the three-way valve output  250 . The pneumatic cylinder  260  drives the piston ring  264  in direction B until the piston ring abuts the extreme left hand end of the chamber  104 . Accordingly, by reciprocating the movement of the cylinder piston arm  262  in a known manner, a quantity of bicarbonate solution is repeatedly dispensed into the bicarbonate mixing pump  108 . Furthermore, by adjusting the position of the removable end stop  270 , the volume of fluid dispensed can be accurately set. The moveable end stop  270  is positioned by a stepper motor or similar accurate positioning drive system. 
         [0110]    The advantage of this system is that the pneumatic cylinder  260  provides the speed of the reciprocating movement required to deliver discrete volumes of fluid into the mixing pump  108  at the required rate. A stepper motor which is extremely accurate but not able to provide the speed reciprocation required, is therefore only used to set the dispense volume of fluid by positioning the moveable end-stop accurately. 
         [0111]    It will be appreciated that the bicarbonate mixing pump  108 , three-way valve  106 , and chamber  104  are provided on the cartridge. However, the remainder of the components described in respect of  FIG. 10  is provided on the dialysis machine. Importantly therefore, the pneumatic cylinder, stepper motor and moveable lens stop are provided on the machine, not the cartridge. 
         [0112]    It will be appreciated that the cartridge of the current invention provides the significant advantage of delivering a homogenous mix of dialysis solution on each and every stroke of the first and second flow balance pumps  152 ,  154 . This feature is critical to delivering a stable dialysis treatment. Furthermore, all of the fluid pathways, pumps and valves required to achieve a homogenous mix are arranged on the cartridge itself. This provides significant advantage since the cartridge contains all of the fluid pathways. 
         [0113]    It is conceivable within the scope of the invention that where the provision of a membrane is not necessary to contain flow within a channel, it is conceivable within the scope of invention that such a section of membrane could be removed from the dialysis cartridge  10  following the application of the membrane sheet on to the outwardly facing surface of the cartridge. 
         [0114]    Additionally, it is conceivable within the scope of invention that certain sections of flow channel may be strengthened for example, by the thickening of the upwardly standing walls, in order to reduce any flexing in the flow channels resulting from the varied hydrostatic pressure in the fluids.