Patent Description:
Patients suffering from reduced kidney function rely on external blood treatments to remove harmful waste substances that build up in their blood over time. One of the most common methods of treatment is haemodialysis. An example of haemodialysis is set out in the applicant's previous application <CIT>.

Haemodialysis typically involves two networks of fluid passageways running adjacent to one another in a counter-current flow arrangement. This arrangement of fluid pathways is provided in a device known as a dialyser. Blood is passed through one set of tubules and dialysis fluid is passed through the other. The pH and osmotic potential of the dialysis fluid is adapted such that waste compounds built up in the blood diffuse from the blood into the dialysis fluid through a semi-permeable membrane which separates the blood and dialysis fluid sides of the network of fluid passageways. Thus the movement of waste compounds is by diffusion, with dialysis fluid moving along the dialyser membrane longitudinally.

Haemodialysis provides a method of gradually removing waste materials with a molecular weight from <NUM> to <NUM> Daltons from the blood by diffusion, minimising fatigue to the patient. However, there are some disadvantages associated with haemodialysis.

One disadvantage of haemodialysis is that medium molecular weight molecules (mMW) dissolved in the blood (for example β-<NUM> microglobulin), which are typically between <NUM> and <NUM> Daltons, are difficult to remove completely from the blood using haemodialysis. It can take a long time to reduce the levels of these substances in the blood to acceptable levels, which may not be convenient for a patient. One other disadvantage of haemodialysis is that molecules can become attached to the semi-permeable membrane, causing a film to build up on the membrane over time. This is detrimental to the operation of the dialyser and the dialysis system as a whole.

An alternative approach to remove waste molecules from the blood is to use a form of convective operation, such as haemodiafiltration.

Classically, haemodiafiltration involves administering sterile dialysis fluid to the blood either by employing a large hydrostatic potential to force sterile dialysis fluid across a semi-permeable membrane into the blood or by directly adding it to the blood; and then pulling the sterile dialysis fluid, complete with dissolved waste products, back across the semi-permeable membrane for subsequent disposal. This type of blood treatment is not limited by diffusion, as sterile dialysis fluid is allowed to mix directly with the blood and returned to the dialysis fluid by a process termed "solute drag". Thus the movement of waste compounds is by convection, with dialysis fluid moving across the dialyser membrane transversely. One known haemodiafiltration method of directly adding dialysis fluid to the blood is controlled by infusing the blood side of the dialyser with sterile solution at a constant flow rate. However, increased patient monitoring may be necessary, and this type of treatment may not suit all patients.

An example of haemodiafiltration is also set out in the applicant's previous applications <CIT> and <CIT>.

Known methods may not allow much control over, or tailoring of, the infusion. Known methods may require extra haemodiafiltration dialysis fluid preparation steps, extra haemodiafiltration dialysis fluid filtration and sterilisation steps, and an additional pump or pumps to move the dialysis fluid independently of the blood pump or pumps.

There is therefore a need for improvements in the above described methods and devices.

According to a first aspect of the present invention there is provided a pump and valve arrangement comprising: a dialyser having a semi-permeable membrane; an inlet pump assembly operable to deliver a first volume of dialysis fluid from a dialysis fluid source to the dialyser in an inlet pump cycle having a dialysis fluid delivery stroke; an outlet pump assembly operable to remove a second volume of dialysis fluid from the dialyser and deliver the second volume of dialysis fluid away from the dialyser in an outlet pump cycle having a dialysis fluid removal stroke; a control system operable to operate the inlet pump assembly in the inlet pump cycle, and operable to operate the outlet pump assembly in the outlet pump cycle, wherein either the control system is further operable to operate the inlet pump assembly in an inlet pump shuttling step additional to the inlet and outlet pump cycles to shuttle the first volume of dialysis fluid between the inlet pump assembly and the dialyser one or more times so as to agitate a surface of the semi-permeable membrane of the dialyser, or the control system is further operable to operate the outlet pump assembly in an outlet pump shuttling step additional to the inlet and outlet pump cycles to shuttle the second volume of dialysis fluid between the outlet pump assembly and the dialyser one or more times so as to agitate a surface of the semi-permeable membrane of the dialyser.

The control system may be further operable to synchronise the inlet pump shuttling step of the inlet pump assembly and the outlet pump shuttling step of the outlet pump assembly so as to shuttle the first volume of dialysis fluid between the inlet pump assembly and the outlet pump assembly via the dialyser one or more times. Transmembrane pressure within the dialyser is thereby unaffected and a greater flow velocity across the entire length of the surface of the semi-permeable membrane of the dialyser may be effected.

The control system may be operable to maintain inactive the other of the inlet pump assembly or the outlet pump assembly when operating the inlet pump assembly to shuttle or operating the outlet pump assembly to shuttle. Transmembrane pressure within the dialyser is thereby affected and a HDF effect is achieved.

The control system may be operable to synchronise the inlet pump shuttling step of the inlet pump assembly and the outlet pump shuttling step of the outlet pump assembly with a delay so as to shuttle the first volume of dialysis fluid between the inlet pump assembly and the outlet pump assembly via the dialyser one or more times. The length of delay may be settable by the control system.

The control system may be operable to synchronise the inlet pump shuttling step of the inlet pump assembly and the outlet pump shuttling step of the outlet pump assembly so as to shuttle the first volume of dialysis fluid between the inlet pump assembly and the dialyser, and the second volume of dialysis fluid between the outlet pump assembly and the dialyser, at the same time, one or more times.

The inlet pump assembly and the outlet pump assembly may both be operable to deliver a first volume of dialysis fluid from a dialysis fluid source to the dialyser and remove a second volume of dialysis fluid from the dialyser. This allows the pumps assembly roles to be swapped.

The control system may be operable to alternate the pump assembly responsible for delivering the first volume of dialysis fluid to the dialyser and the pump assembly responsible for removing the second volume of dialysis fluid from the dialyser after a given number of inlet pump cycles.

Each of the inlet pump assembly and the outlet pump assembly may be defined in part by a flexible membrane, the flexible membrane may be independently operable between an open position and a closed position for each of the inlet pump assembly and the outlet pump assembly.

The inlet pump assembly may comprise a first pump operable to deliver a volume of dialysis fluid from a dialysis fluid source to the dialyser, a first dialyser inlet valve arranged between the first pump and an inlet of the dialyser and a first dialyser outlet valve arranged between an outlet of the dialyser and the first pump, wherein each of the valves and pumps are independently operable.

The outlet pump assembly may comprise a second pump for operable to remove a volume of dialysis fluid from the dialyser and deliver said dialysis fluid to a drain, a second dialyser outlet valve arranged between an outlet of the dialyser and the second pump and a second dialyser inlet valve arranged between the second pump and an inlet of the dialyser, wherein each of the valves and pumps are independently operable.

The pump and valve arrangement may further comprise a first dialysis fluid source valve arranged between the dialysis fluid source and the first pump.

The pump and valve arrangement may further comprise a second dialysis fluid source valve arranged between the dialysis fluid source and the second pump.

The pump and valve arrangement may further comprise a first drain valve arranged between the first pump and the drain.

The pump and valve arrangement may further comprise a second drain valve arranged between the second pump and the drain.

According to a second aspect of the present invention there is provided a dialysis system comprising the pump and valve arrangement according to the first aspect of the invention.

According to a third aspect of the present invention there is provided a method of cleaning a semi-permeable membrane of a dialyser, the method comprising the steps of: providing a pump and valve arrangement, the pump and valve arrangement comprising the dialyser having the semi-permeable membrane, an inlet pump assembly, an outlet pump assembly, a blood circuit and a control system; providing a source of blood analogue fluid and supplying the blood analogue fluid to the blood circuit; operating the inlet pump assembly in an inlet pump assembly cycle to deliver a first volume of a cleaning fluid from a cleaning fluid source to the dialyser, each inlet pump assembly cycle including a cleaning fluid delivery stroke; operating the outlet pump assembly in an outlet pump assembly cycle to remove a second volume of the cleaning fluid from the dialyser and draw the second volume of cleaning fluid away from the dialyser <NUM>, each outlet pump assembly cycle including a cleaning fluid removal stroke; and either operating the inlet pump assembly in a shuttle cycle, to shuttle the first volume of cleaning fluid between the inlet pump assembly and the dialyser <NUM> one or more times before the cleaning fluid delivery stroke, or operating the outlet pump assembly in a shuttle cycle, to shuttle the second volume of cleaning fluid between the outlet pump assembly and the dialyser <NUM> one or more times before the cleaning fluid removal stroke.

Any fluid may be used as the cleaning fluid. For instance, in some embodiments water may be used as the cleaning fluid. In other embodiments the cleaning fluid may comprise a solution, for instance a dialysate solution, or a solution containing a detergent.

Any fluid can be used as the blood analogue fluid. For instance, the blood analogue fluid may be water. Alternatively, the blood analogue fluid is a fluid designed to behave in a similar fashion to blood to enable the device to be tested. Blood plasma may be used as the analogue fluid. The blood analogue fluid may include a marker, such as a dye or a marker molecule which may be sensed using appropriate sensors.

The method may comprise the further step of operating the outlet pump assembly in a shuttle cycle, to shuttle the second volume of cleaning fluid between the outlet pump assembly and the dialyser one or more times before the cleaning fluid removal stroke.

The method may comprise the further step of synchronising the operations of the inlet pump assembly and outlet pump assembly so as to shuttle the first volume of cleaning fluid between the inlet pump assembly and the outlet pump assembly via the dialyser one or more times before the cleaning fluid delivery stroke.

The method may comprise the further step of maintaining inactive the other of the inlet pump assembly or the outlet pump assembly when operating the inlet pump assembly to shuttle or operating the outlet pump assembly to shuttle.

The method may comprise the further step of synchronising the operations of the inlet pump assembly and outlet pump assembly with a delay so as to shuttle the first volume of cleaning fluid between the inlet pump assembly and the outlet pump assembly via the dialyser <NUM> one or more times before the cleaning fluid delivery stroke.

The method may comprise synchronising the operations of the inlet pump assembly and outlet pump assembly so as to shuttle the first volume of cleaning fluid between the inlet pump assembly and the dialyser, and the second volume of cleaning fluid between the outlet pump assembly and the dialyser, at the same time, one or more times.

The inlet pump assembly and outlet pump assembly may both be operable to deliver a first volume of cleaning fluid from a cleaning fluid source to the dialyser and remove a second volume of cleaning fluid from the dialyser and deliver said cleaning fluid to a drain.

The method may comprise the further step of alternating the pump responsible for delivering the first volume of cleaning fluid to the dialyser and the pump responsible for removing the second volume of cleaning fluid from the dialyser after a given number of cycles.

The given number of cycles may be between <NUM> and <NUM>. The given number of cycles may be <NUM>.

Embodiments of the present invention will now be described, by non-limiting example only, with reference to the accompanying drawings, in which:.

The following detailed description and figures provide examples of how the present invention can be implemented and should not be seen as limiting examples, rather illustrations of how the various features of the convective operation device disclosed herein can be used. Other optional variations will be evident upon a reading of the following description in light of the figures.

Referring to <FIG> and <FIG>, a dialysis system, generally referred to as <NUM>, is shown. A dialyser <NUM> receives blood via an arterial line <NUM> connected to a patient by a vascular access device (not shown for clarity), for example a hollow needle as typically used for drawing blood from a patient. The blood is pumped from the patient to the dialyser by a peristaltic pump <NUM>. The blood passes through the dialyser in a known manner and is returned to the patient via a venous line <NUM>. The dialyser <NUM> comprises a cylindrical tube closed by opposing ends. A semi-permeable membrane (not shown) is provided within the dialyser tube and separates the patient's blood from a dialysis fluid. The term "dialysis fluid" used herein does not require that a solution designed to clinical tolerances be used, however a solution designed to within clinical tolerances may be advantageous. The membrane extends substantially between the opposing ends of the cylinder. The dialysis fluid solution removes impurities from the patient's blood in a known manner.

The dialyser has a dialysis fluid solution inlet <NUM> for receiving clean dialysis fluid solution and a dialysis fluid solution outlet <NUM> for removing spent dialysis fluid solution from the dialyser <NUM>. The dialyser also has a blood inlet <NUM> for receiving untreated blood from the peristaltic pump <NUM> and a blood outlet <NUM> for returning processed blood to the patient. The dialyser <NUM> is typically provided in a substantially upright orientation, in use, with the patient's blood flowing longitudinally through the dialyser <NUM> from the blood inlet <NUM> to the blood outlet <NUM>. The dialysis fluid solution inlet <NUM> and dialysis fluid solution outlet <NUM> are configured to be orientated substantially orthogonal to the blood inlet <NUM> and blood outlet <NUM>, and configured to provide a counter-flow. Dialysis fluid solution is circulated through the hemodialysis machine at a fluid flow rate typically in the range of <NUM>/min to <NUM>/min for approximately four hours.

The dialysis system defines a fluid circuit including a cartridge <NUM> as will now be described. The cartridge <NUM> is a consumable component in the hemodialysis machine described.

The cartridge <NUM> is formed from an acrylic plastic such as SG-<NUM> and has a machine side and a patient side. The cartridge <NUM> defines pump chambers which are closed by respective diaphragms, formed from, for example, DEHP-free PVC, to define respective pumps. In this embodiment, each diaphragm is part of a single, common sheet of material applied to the machine side of the cartridge <NUM>. The individual diaphragms are operable by pneumatic pressure applied thereto.

A series of flow paths are formed in the cartridge <NUM> for carrying dialysis fluid solution constituted from water, bicarbonate solution and acid solution. The bicarbonate may be provided from a bicarbonate source <NUM> fluidly connected to the cartridge <NUM> and the acid from an acid source fluidly connected to the cartridge <NUM>. The flow paths are located between the sheet of material closing the machine side of the cartridge <NUM> and a further sheet of the same material closing the patient side of the cartridge <NUM>.

In use, the variation of pressure applied to the flexible diaphragm of each pump chamber is controlled by conventional valving. A pressure source applies either a positive or negative pressure to one side of the diaphragm of each pump chamber, as required, to pump fluid through the fluid paths in the cartridge <NUM>, in a circuit defined by a plurality of valves.

The valves of the cartridge <NUM> are diaphragm valves defined by respective openings in the cartridge <NUM> and closed by respective flexible diaphragms. Each valve is operable by applying a negative pressure to the diaphragm to open the valve and applying a positive pressure to the diaphragm to close the valve. The diaphragm of each valve is part of the single, common sheet of material applied to the machine side of the cartridge <NUM>. The valves are opened and closed according to a flow control strategy, as will become apparent.

The machine side of the cartridge <NUM> abuts a pump driver (not shown) comprising a platen having a plurality of recessed surfaces, each recessed surface substantially corresponding in geometry and volume to a pump chamber defined in the cartridge <NUM>. Each recessed surface has a fluid port connectable with a source of positive fluid, typically, pressure and, with a source of negative fluid pressure via a valve.

A cartridge fluid pump and corresponding platen chamber are shown in <FIG>. The positive and negative fluid pressure sources <NUM> include a pressure pump and a vacuum pump respectively. When the valve is operated to allow fluid to flow via channel <NUM> into a recessed surface from the source of positive fluid pressure, the flexible membrane or diaphragm <NUM> moves into a corresponding pump chamber <NUM> and any fluid, i.e. dialysis fluid solution, therein is expelled from that pump chamber via the series of flow paths <NUM>, <NUM>. The direction of flow through flow paths <NUM>, <NUM> being determined by valves (not shown). This flexible membrane or diaphragm <NUM> position is shown by dotted line <NUM>. When the valve is operated to allow fluid to flow out of a recessed surface to the source of negative fluid pressure, the flexible membrane or diaphragm <NUM> is moved away from the pump chamber <NUM> and into the corresponding recessed surface <NUM> to permit fluid to be drawn into that pump chamber via the series of flow paths <NUM>, <NUM>. This flexible membrane or diaphragm <NUM> position is shown by the dotted line <NUM>. The surface of the pump chambers and of the platen provide a positive stop for each diaphragm <NUM>, to prevent overstretching thereof. The positive stop ensures that the volume of fluid drawn into and pumped from the pump chambers is accurately controlled.

The cartridge <NUM> has two main functions, preparation of dialysis fluid solution and flow balance. Each function is performed by a separate part of the cartridge as illustrated in <FIG> and <FIG> by the schematic separation of the cartridge into two parts by the line A- A in the figures. The dialysis fluid preparation function is performed by one part of the cartridge, generally referred to at <NUM> and the flow balance function is performed by the other part of the cartridge, generally referred to at <NUM>. The cartridge <NUM> prepares an accurately mixed homogenous dialysis fluid solution and ensures that the flow of clean dialysis fluid supplied to the dialyser <NUM> matches (to within clinical tolerances) the volume of spent dialysis fluid drawn from the dialyser <NUM>.

The cartridge <NUM> is provided with a plurality of connections to and from the cartridge <NUM> as described below. A first inlet port <NUM>, from hereon referred to as the water inlet port, defined in the machine side of the cartridge <NUM> receives purified water from a purified water supply <NUM> such as a reverse osmosis water supply.

A first outlet port <NUM>, from hereon referred to as the water outlet port, defined in an edge of the cartridge <NUM> directs the purified water to a first dialysis fluid solution constituent which, in the illustrated embodiment shown in <FIG> and <FIG>, is bicarbonate in bicarbonate source <NUM>.

A second inlet port <NUM>, from hereon referred to as the bicarbonate inlet port, defined in the same edge of the cartridge <NUM> as the water outlet port <NUM> receives purified water mixed with the bicarbonate from the bicarbonate source <NUM>.

A third inlet port <NUM>, from hereon referred to as the acid inlet port, defined in the opposite edge of the cartridge <NUM> to the water outlet port <NUM> and bicarbonate inlet port <NUM> receives a second dialysis fluid solution constituent which, in the illustrated embodiment shown in <FIG> and <FIG>, is acid from acid source <NUM>.

A second outlet port <NUM>, from hereon referred to as the clean dialysis fluid solution outlet port, is defined in the same edge of the cartridge as the water outlet port <NUM> and the bicarbonate inlet port <NUM>. The clean dialysis fluid outlet port <NUM> directs clean dialysis fluid solution to the dialyser <NUM>.

A fourth inlet port <NUM>, from hereon referred to as the spent dialysis fluid solution inlet port, is defined in the same edge of the cartridge <NUM> as the water outlet port <NUM>, bicarbonate inlet port <NUM> and clean dialysis fluid outlet port <NUM>. The spent dialysis fluid solution inlet port <NUM> receives spent dialysis fluid solution from the dialyser <NUM>.

A third outlet port <NUM>, from hereon referred to as the drain port, is defined in the same edge of the cartridge as the acid inlet port <NUM>. The drain port <NUM> directs spent dialysis fluid solution out of the cartridge <NUM>.

<FIG> shows a schematic representation of the pump and valve arrangement <NUM> of the invention. In this case, the pump and valve arrangement <NUM> is provided by the combination of a membrane pump cartridge (or part cartridge) and a vacuum pump array with platen. The membrane pump cartridge is similar in layout to the flow balance pump arrangement described above.

The membrane pump cartridge comprises first and second dialysis fluid source valves <NUM>, <NUM>, first and second pumps <NUM>, <NUM> and first and second pump chambers <NUM>, <NUM>, first and second dialyser inlet valves <NUM>, <NUM>, first and second dialyser outlet valves <NUM>, <NUM> and first and second drain valves <NUM>, <NUM>.

The vacuum pump array and platen comprises a platen having a pattern of circular depressions which correspond in position and size to the valves and pumps on the pump cartridge. In the figure, these are numbered <NUM> higher than the membrane pump features.

Each depression has an aperture at the base thereof which is in fluid communication with an associated vacuum pump. Each vacuum pump, shown in broken lines as they sit on the rear face of the platen, is numbered <NUM> higher than the respective associated platen feature.

All of the vacuum pumps are connected to a control system <NUM>. The control system <NUM> is a microprocessor which operates the vacuum pumps <NUM>-<NUM> in a manner so as to effect either convective operation or haemodialysis as described below. The connection to the pumps may be wired or wireless. Wireless connection options include IR, Bluetooth or WIFI, amongst others.

The dialysis fluid is produced elsewhere on the cartridge by mixing acid and bicarbonate compounds with a set volume of water provided by a reverse osmosis machine which has been sterilized. This forms the dialysis fluid source <NUM> shown schematically in <FIG> which is used by the pump and valve arrangement <NUM>. Also shown schematically in <FIG> is a drain <NUM>. Both the dialysis fluid source <NUM> and the drain <NUM> are fluidly connectable to the first pump chamber <NUM> and the second pump chamber <NUM>.

All valves and pumps are independently operable. In one embodiment, all pumps <NUM>, <NUM> and all valves <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM> are independently operable by pneumatic pressure applied to the flexible membrane.

By selectively operating the vacuum pumps, the control system controls the opening and closure of the valves as well as actuation of the first and second pumps. The microprocessor control system is programmable to operate the valves in a variety of different configurations. Based on the programming of the control system <NUM>, the control system <NUM> will communicate with each of the valves or means for operating the valves, so that each valve may be opened and closed independently based on the programming entered into the control system <NUM> by the user, skilled operator or program instructions.

The apparatus described can be used in two different modes: haemodialysis (HD) mode and haemodiafiltration (HDF) mode, as will be described in more detail below.

A Haemodialysis (HD) mode pumping cycle of the arrangement <NUM> begins with closure of the first and second dialyser inlet valves <NUM>, <NUM> and the first and second dialyser outlet valves <NUM>, <NUM>. The first dialysis fluid source valve <NUM> and the second drain valve <NUM> are opened, the second source valve <NUM> and first drain valve <NUM> are closed. The first pump <NUM> is then operated to draw dialysis fluid from the dialysis fluid source <NUM> into the first pump chamber <NUM> of the first pump <NUM> and the second pump <NUM> is operates to expel dialysis fluid within the second pump chamber <NUM> of the second pump <NUM> into the drain <NUM>.

Accordingly, the dialysis fluid in the dialysis fluid source <NUM> is drawn into the first pump chamber <NUM> by the negative pressure created as the membrane of the first pump chamber <NUM> is drawn away from the pump chamber by vacuum means in the dialysis machine (not shown). The dialysis fluid in the second pump chamber <NUM> is subjected to a positive pressure as the membrane in the second pump <NUM> is forced into the second pump chamber <NUM> thus driving the dialysis fluid out through the open second drain valve <NUM> to be discarded.

Thus before commencement of the dialyser pumping cycle, the first pump chamber <NUM> is filled with fresh dialysis fluid and the second pump chamber <NUM> is emptied of spent dialysis fluid.

In the first step of the pump cycle, the first dialyser inlet valve <NUM> and the second dialyser outlet valve <NUM> are opened and the first dialysis fluid source valve <NUM> and the second drain valve <NUM> are closed. The first pump <NUM> is then actuated to expel the dialysis fluid from within the first pump chamber <NUM> into the dialyser <NUM> (not shown in <FIG>) and simultaneously the second pump <NUM> is actuated to pull spent dialysis fluid from the dialyser <NUM> into the second pump chamber <NUM>. In this step, the dialysis fluid in the first pump chamber <NUM> has a positive pressure applied to it as the membrane is forced down into the first pump chamber <NUM> thereby forcing the dialysis fluid through the dialysis circuit and into the dialyser. In the dialyser <NUM>, dialysis fluid is passed in a counterflow arrangement to the blood of the patient and waste products diffuse across the dialyser membrane into the dialysis fluid via diffusion. The movement of the dialysis fluid through the dialyser <NUM> and into the second pump chamber <NUM> is assisted by a negative pressure generated by the membrane of the second pump chamber which is retracted by the vacuum means on the dialysis machine, operated by the control system <NUM>.

Thus in step <NUM> the first pump chamber <NUM> delivers fresh dialysis fluid to the dialyser <NUM> in a dialysis fluid delivery stroke and simultaneously the second pump chamber <NUM> draws spent dialysis fluid from the dialyser <NUM> in a dialysis fluid removal stroke.

As such the first pump <NUM>, first dialyser inlet valve <NUM>, and the first source valve <NUM> comprise an inlet pump assembly configured to deliver a first volume of dialysis fluid from the dialysis fluid source <NUM> to the dialyser in an inlet pump cycle having a dialysis fluid delivery stroke, and the second pump <NUM>, second dialyser outlet valve <NUM> and the second drain valve <NUM> comprise an outlet pump assembly configured to remove a second volume of dialysis fluid from the dialyser and deliver the dialysis fluid away from the dialyser in an outlet pump cycle having a dialysis fluid removal stroke.

In step <NUM> of the pump cycle, the first dialyser inlet valve <NUM> and second dialyser outlet valve <NUM> are closed, the second drain valve <NUM> is opened and second pump <NUM> actuated to expel the spent dialysis fluid from the second pump chamber <NUM> into the drain <NUM>.

Steps <NUM> and <NUM> are repeated <NUM> times.

Accordingly, after the completion of step <NUM>, both pump chambers <NUM>, <NUM> are empty.

The roles of the first and second pumps <NUM>, <NUM> can then be reversed. In order to enact the pump swap, the contents of the first pump <NUM> are expelled to drain <NUM> (step <NUM>) and then the second drain valve <NUM> is closed and the second source valve <NUM> is opened in order to allow the second pump <NUM> to draw dialysis fluid from the dialysis fluid source <NUM> into the second pump chamber <NUM>.

In step <NUM>, with the second pump chamber <NUM> now filled, the second dialyser inlet valve <NUM> the first dialyser outlet valves <NUM> are opened and the second dialysis fluid source valve <NUM> is closed. The second pump <NUM> is actuated to expel the dialysis fluid in the second pump chamber <NUM> into the dialyser <NUM> and the first pump <NUM> is actuated to draw dialysis fluid from the dialyser <NUM> into the first pump chamber <NUM>. This allows the same operation as was carried out in steps <NUM> and <NUM> to proceed but with the roles of the pumps <NUM>, <NUM> swapped around. Thus any small discrepancies between the volumes of the two pump chambers <NUM>, <NUM> are cancelled out.

As such the second pump <NUM>, second dialyser inlet valve <NUM>, and the second dialysis fluid source valve <NUM> comprise an inlet pump assembly configured to deliver a first volume of dialysis fluid from the dialysis fluid source <NUM> to the dialyser in an inlet pump cycle having a dialysis fluid delivery stroke, and the first pump <NUM>, first dialyser outlet valve <NUM> and the first drain valve <NUM> comprise an outlet pump assembly configured to remove a second volume of dialysis fluid from the dialyser and deliver the dialysis fluid away from the dialyser in an outlet pump cycle having a dialysis fluid removal stroke.

In step <NUM> the first dialyser outlet valve <NUM> and second dialyser inlet valve <NUM> are closed, the first drain valve <NUM> and second dialysis fluid source valve <NUM> are opened and the first pump <NUM> is operated to expel the dialysis fluid from the first pump chamber <NUM> into the drain <NUM> whilst the second pump <NUM> draws dialysis fluid from the dialysis fluid source <NUM> into the second pump chamber <NUM>.

Steps <NUM> to <NUM> are repeated <NUM> times.

The pumping cycle of the Haemodialysis (HD) mode of operation is summarised in table <NUM> below.

The pumping cycle of the Haemodialysis (HD) mode of operation gives a flow rate of <NUM>/min through the dialyser when the pump chambers <NUM>, <NUM> are sized to <NUM> and operated at a frequency of <NUM>. There is no dwell time at this rate, i.e. the duty cycle is <NUM>%.

For pumping cycles where a lower flow rate is required, a number of pauses may be introduced into the pumping sequence. This is because at lower flow rates the fill and empty time of the first and second pump chambers <NUM>, <NUM> remains the same and the duty cycle is reduced. Thus there is a period of time available when there is no net flow into and out of the dialysis fluid side of the dialyser <NUM>, and the first pump <NUM> and the second pump <NUM> are effectively paused.

For example if the dialysis fluid flow rate is reduced to <NUM>% (<NUM>/min) then the first pump <NUM> and the second pump <NUM> are effectively paused for <NUM>% of the time.

At all times blood on the blood side of the dialyser <NUM> continues to flow through the dialyser <NUM>.

Therefore the duty cycle of the pumps <NUM>, <NUM> is reduced to achieve lower dialysis fluid flow rates through the dialyser.

Referring to <FIG>, two idealized schematics for flow to and from the dialyser according to different pumping regimes are shown.

<FIG> shows a normal flow rate pumping regime <NUM>, with flow to the dialyser <NUM> shown on the positive y-axis <NUM>, flow from the dialyser <NUM> shown on the negative y-axis <NUM> and time shown on the x-axis <NUM>. The dashed line <NUM> represents the first pump <NUM> flow. The dotted line <NUM> represent second pump <NUM> flow.

As previously described in Table <NUM>, for normal haemodialysis treatment, the pump cycles are synchronized such that as first pump <NUM> pumps dialysis fluid to the dialyser <NUM>, second pump <NUM> draws dialysis fluid from the dialyser <NUM>, (step <NUM>). This is represented by the two square forms identified as <NUM> for flow to the dialyser <NUM> and <NUM> for flow from the dialyser <NUM>. Then, as first pump <NUM> draws dialysis fluid from the dialysis fluid source <NUM>, second pump <NUM> expels dialysis fluid to the drain <NUM> (step <NUM>) there is no flow to and from the dialyser <NUM>, represented by the flat forms generally identified as <NUM>. This pumping cycle <NUM> is repeated six times.

<FIG> shows a lower flow rate pumping regime <NUM>. Similar reference numerals are used throughout, pre-fixed with a "<NUM>" rather than a "<NUM>" to indicate that those reference numerals relate to the lower flow rate pumping regime <NUM> rather than the normal flow rate pumping regime <NUM>.

In the same time period as for the normal flow rate pumping regime <NUM>, the lower flow rate pumping regime <NUM> has only a single pumping cycle <NUM>. The single pumping cycle <NUM> is preceded by a period of time where there is no flow to and from the dialyser <NUM>, represented by the elongate flat section <NUM> of lines <NUM>, <NUM> of the first pump <NUM> flow and the second pump <NUM> flow. Thus the duty cycle of the lower flow rate pumping regime <NUM> is <NUM>% as compared to the <NUM>% duty cycle of the normal flow rate pumping regime <NUM>.

In a pumping cycle of the present invention, additional shuttling pump steps are added. The movement of the dialysis fluid is referred to as longitudinal with respect to the semi-permeable membrane of the dialyser <NUM>.

Thus new steps 1a and 1b are effected ahead of the dialyser flow step (step <NUM>). Most importantly, these shuttling pump steps are timed to occur whilst the first pump <NUM> and the second pump <NUM> would have otherwise been paused.

The new steps 1a and 1b are known as shuttling steps. These increase flow of dialysis fluid along the semi-permeable membrane of the dialyser <NUM>.

The shuttling steps may take place irrespective of which pump <NUM>, <NUM> is being used to expel dialysis fluid to the dialyser <NUM>. As such, for simplicity, Table <NUM> does not show the shuttling steps for the pumping cycle second pump <NUM> to first pump <NUM>, nor the pump swap steps.

The new steps 1a and 1b may be performed one or more times. For example for the <NUM>% duty cycle discussed above, <NUM>% of the time may be used for shuttling (i.e. step 2a followed by step 2b).

Because Steps 1a and 1b synchronise the operation of the first pump <NUM> and the second pump <NUM>, there is no change in transmembrane pressure in the dialyser <NUM>. There is a large change in flow along the dialyser membrane which acts to agitate and wash the surface of the dialyser membrane.

<FIG> shows the lower flow rate pumping regime of <FIG>, however with the addition of <NUM> shuttling steps. Similar reference numerals are used throughout, pre-fixed with a "<NUM>" rather than a "<NUM>" to indicate that those reference numerals relate to a lower flow rate pumping regime with HD shuttling <NUM> rather than the lower flow rate pumping regime <NUM>.

In the same time period as for the normal flow rate pumping regime <NUM>, and the lower flow rate pumping regime <NUM>, the lower flow rate pumping cycle with HD shuttling <NUM> has only a single pumping cycle <NUM>. The single pumping cycle <NUM> is preceded by a period of time where shuttling occurs, generally designated <NUM>.

Specifically, the first pump <NUM> expels dialysis fluid to the dialyser <NUM>, with the dashed line <NUM> representing the first pump <NUM> flow returning a positive y-axis <NUM> value. At the same time the second pump <NUM> draws dialysis fluid from the dialyser <NUM>, with the dotted line <NUM> representing the second pump <NUM> flow returning a negative y-axis <NUM> value, (step 1a).

Subsequently, the first pump <NUM> draws dialysis fluid from the dialyser <NUM>, with the dashed line <NUM> representing the first pump <NUM> flow returning a negative y-axis <NUM> value. At the same time the second pump <NUM> expels dialysis fluid to the dialyser <NUM>, with the dotted line <NUM> representing the second pump <NUM> flow returning a positive y-axis <NUM> value, (step 1b).

This double pump shuttle sequence <NUM> is repeated five times in total. During this double pump shuttle sequence <NUM>, dialysis fluid is not entering or leaving the dialysis system, the dialysis fluid is agitating a surface of the semi-permeable membrane of the dialyser <NUM>.

The same pump and valve arrangement <NUM> may be used to effect haemodiafiltration (HDF). In HDF dialysis fluid is forced across the semi-permeable membrane of the dialyser <NUM> from the dialysis fluid side to the blood side, and vice-versa in order to provide additional clearance through convection.

In contrast to the haemodialysis modes described above, the shuttling steps may not operate with pump movements that are directly synchronised with each other. Instead, some pump movements are split between the pauses, or dwell times when otherwise no pumps would be actuated. The movement of the dialysis fluid is referred to as transverse with respect to the semi-permeable membrane of the dialyser <NUM>.

The new steps 1a and 1b may be performed one or more times.

As such, for the steps 1a and 1b, the first pump <NUM>, first dialyser inlet valve <NUM>, and the first source valve <NUM> comprise an inlet pump assembly configured to deliver a first volume of dialysis fluid from the dialysis fluid source <NUM> to the dialyser <NUM> in an inlet pump cycle having a dialysis fluid delivery stroke and the same pump and valves additionally comprise the inlet pump assembly configured to shuttle dialysis fluid between the inlet pump assembly and the dialyser <NUM> one or more times so as to agitate the surface of the semi-permeable membrane of the dialyser <NUM>. That is a reverse flow is permitted through the first dialyser inlet valve <NUM>. Alternatively the first dialyser outlet valve <NUM> may be used to permit the shuttling flow from the dialyser <NUM> to the inlet pump assembly.

Because steps 1a and 1b split the operation of the first pump <NUM> and the second pump <NUM>, there is a change in transmembrane pressure in the dialyser according to the In-Flow and the Out-Flow. This provides and enhanced HDF effect as well as generally agitating and scrubbing the semi-permeable membrane of the dialyser.

Not shown in the Table <NUM>, but equally possible, HDF shuttling may alternatively be achieved using the second pump <NUM>. That is, the second pump <NUM>, second dialyser inlet valve <NUM>, and the second source valve <NUM> comprise an inlet pump assembly configured to deliver a first volume of dialysis fluid from the dialysis fluid source <NUM> to the dialyser in an inlet pump cycle having a dialysis fluid delivery stroke, and the same pump and valves additionally comprise the inlet pump assembly configured to shuttle dialysis fluid between the inlet pump assembly and the dialyser one or more times so as to agitate the surface of the semi-permeable membrane of the dialyser. That is a reverse flow is permitted through the second dialyser inlet valve <NUM>. Alternatively the second dialyser outlet valve <NUM> may be used to permit the shuttling flow from the dialyser <NUM> to the inlet pump assembly.

As will be understood, it is not essential to use both the first pump <NUM> and the second pump <NUM> for the shuttling steps, as flow balance remains unaffected.

<FIG> shows the lower flow rate pumping cycle of <FIG>, however with the addition of <NUM> shuttling steps. Similar reference numerals are used throughout, pre-fixed with a "<NUM>" rather than a "<NUM>" to indicate that those reference numerals relate to a lower flow rate pumping cycle with HDF shuttling <NUM> rather than the lower flow rate pumping cycle <NUM>.

In the same time period as for the normal flow rate pumping cycle <NUM>, and the lower flow rate pumping cycle <NUM>, the lower flow rate pumping cycle with HDF shuttling <NUM> has only a single pumping cycle <NUM>. The single pumping cycle <NUM> is preceded by a period of time where HDF shuttling occurs, generally designated <NUM>.

Specifically, the first pump <NUM> expels dialysis fluid to the dialyser <NUM>, with the dashed line <NUM> representing the first pump <NUM> flow returning a positive y-axis <NUM> value. At the same time, for the first iteration only the second pump <NUM> draws dialysis fluid from the dialyser <NUM>, with the dotted line <NUM> representing the second pump <NUM> flow returning a negative y-axis <NUM> value.

From then on, for each time the first pump <NUM> expels dialysis fluid to the dialyser <NUM>, the second pump <NUM> is inactive, with the dotted line <NUM> representing the second pump <NUM> flow returning a zero y-axis <NUM> value (step 1a).

Subsequently, the first pump <NUM> draws dialysis fluid from the dialyser <NUM>, with the dashed line <NUM> representing the first pump <NUM> flow returning a negative y-axis <NUM> value. At the same time the second pump <NUM> remains inactive (step 1b).

This single pump shuttle sequence <NUM> is repeated four times in total. During this single pump shuttle sequence <NUM>, dialysis fluid is entering and leaving the dialysis system across the semi-permeable membrane of the dialyser <NUM>, as well as agitating a surface of the semi-permeable membrane of the dialyser <NUM>.

Just as the inlet pump assembly may be configured to shuttle dialysis fluid between the inlet pump assembly and the dialyser one or more times, so can the outlet pump assembly.

In the case of the first pump <NUM>, either the flow through the first dialyser outlet valve <NUM> can be reversed to return dialysis fluid to the dialyser <NUM> or the first dialyser inlet valve <NUM> may be used.

In the case of the second pump <NUM>, the flow through the second dialyser outlet valve <NUM> can be reversed to return dialysis fluid to the dialyser <NUM> or the second dialyser inlet valve <NUM> may be used.

When using the outlet pump assembly to shuttle dialysis fluid, the dialysis fluid is partially spent dialysis fluid.

<FIG> shows the lower flow rate pumping cycle of <FIG>, however with the addition of <NUM> shuttling steps. Similar reference numerals are used throughout, pre-fixed with a "<NUM>" rather than a "<NUM>" to indicate that those reference numerals relate to a lower flow rate pumping cycle with phased shuttling <NUM> rather than the lower flow rate pumping cycle <NUM>.

In the same time period as for the normal flow rate pumping cycle <NUM>, and the lower flow rate pumping cycle <NUM>, the lower flow rate pumping cycle with phased shuttling <NUM> has only a single pumping cycle <NUM>. The single pumping cycle <NUM> is preceded by a period of time where phased shuttling occurs, generally designated <NUM>.

Specifically, the first pump <NUM> expels dialysis fluid to the dialyser <NUM>, with the dashed line <NUM> representing the first pump <NUM> flow returning a positive y-axis <NUM> value. At the same time for the first iteration only the second pump <NUM> draws dialysis fluid from the dialyser <NUM>, with the dotted line <NUM> representing the second pump <NUM> flow returning a negative y-axis <NUM> value.

Subsequently, the first pump <NUM> draws dialysis fluid from the dialyser <NUM>, with the dashed line <NUM> representing the first pump <NUM> flow returning a negative y-axis <NUM> value. At the same time for the first iteration only the second pump <NUM> expels dialysis fluid to the dialyser <NUM>, with the dotted line <NUM> representing the second pump <NUM> flow returning a positive y-axis <NUM> value. However the second pump <NUM> terminates the expulsion of dialysis fluid to the dialyser <NUM> ahead of the first pump <NUM> finishing drawing dialysis fluid from the dialyser <NUM>, shown by the gap between the vertical portions of the dashed line <NUM> representing the first pump <NUM> flow and the dotted line <NUM> represent second pump <NUM> flow. This delay or gap defines a period of transverse in-flow <NUM> across the dialyser membrane when waste compounds are dragged from a patient side of the dialyser membrane to a dialysis fluid side of the dialyser membrane by convection. This is because the second pump begins to draw dialysis fluid from the dialyser <NUM> at the same time that the first pump <NUM> continues to draw dialysis fluid from the dialyser <NUM>.

This is followed by a period of longitudinal flow <NUM>, where the first pump <NUM> and the second pump <NUM> are in-phase and therefore act in a similar manner to the double pump shuttle sequence <NUM> described with respect to <FIG>.

However, as the, second pump <NUM> expels dialysis fluid to the dialyser <NUM> before the first pump <NUM> commences to draw dialysis fluid from the dialyser <NUM>, another gap is defined, this time as a period of transverse out-flow <NUM> across the dialyser membrane when dialysate is forcibly returned to the patient side of the dialyser membrane from the dialysis fluid side of the dialyser membrane.

Thus during the period of transverse in-flow <NUM> and the period of transverse out-flow <NUM>, the first pump <NUM> and the second pump <NUM> are out of phase and a HDF effect is caused, with the associated change in transmembrane pressure.

Conversely, in the remainder of the low flow phased shuttle sequence <NUM>, defined as the two separate periods of longitudinal flow <NUM>, the first pump <NUM> and the second pump <NUM> are in phase and thus there is only longitudinal flow along the dialysis membrane.

During this phased shuttle sequence <NUM>, a combined effect is achieved with dialysis fluid is entering and leaving the dialysis system across the semi-permeable membrane of the dialyser <NUM> (transverse flow), as well as agitating a surface of the semi-permeable membrane of the dialyser <NUM> (longitudinal flow).

The ratio of longitudinal flow versus transverse flow is variable, by altering the size of the period of transverse in-flow <NUM> and the period of transverse out-flow <NUM> relative to the two periods of longitudinal flow <NUM> in each phased shuttle sequence <NUM>. The control system <NUM> may be configured to set this ratio.

<FIG> shows the lower flow rate pumping cycle of <FIG>, however with the addition of <NUM> shuttling steps. Similar reference numerals are used throughout, pre-fixed with a "<NUM>" rather than a "<NUM>" to indicate that those reference numerals relate to a lower flow rate pumping cycle with HDF twin pump shuttling <NUM> rather than the lower flow rate pumping cycle <NUM>.

In the same time period as for the normal flow rate pumping cycle <NUM>, and the lower flow rate pumping cycle <NUM>, the lower flow rate pumping cycle with HDF twin pump shuttling <NUM> has only a single pumping cycle <NUM>. The single pumping cycle <NUM> is preceded by a period of time where HDF twin pump shuttling occurs, generally designated <NUM>.

From then on, for each time the first pump <NUM> expels dialysis fluid to the dialyser <NUM>, the second pump <NUM> also expels dialysis fluid to the dialyser <NUM> (step <NUM>). Subsequently, the first pump <NUM> draws dialysis fluid from the dialyser <NUM>, with the dashed line <NUM> representing the first pump <NUM> flow returning a negative y-axis <NUM> value. At the same time the second pump <NUM> draws dialysis fluid from the dialyser <NUM> (step <NUM>).

Claim 1:
A pump and valve arrangement (<NUM>) comprising:
a dialyser (<NUM>) having a semi-permeable membrane;
an inlet pump assembly operable to deliver a first volume of dialysis fluid from a dialysis fluid source to the dialyser (<NUM>) in an inlet pump cycle having a dialysis fluid delivery stroke;
an outlet pump assembly operable to remove a second volume of dialysis fluid from the dialyser (<NUM>) and deliver the second volume of dialysis fluid away from the dialyser (<NUM>) in an outlet pump cycle having a dialysis fluid removal stroke;
a control system (<NUM>) operable to operate the inlet pump assembly in the inlet pump cycle, and operable to operate the outlet pump assembly in the outlet pump cycle, wherein for each inlet pump cycle there is a corresponding outlet pump cycle, characterized in that either
the control system is further operable to operate the inlet pump assembly in an inlet pump shuttling step additional to the inlet and outlet pump cycles to shuttle the first volume of dialysis fluid between the inlet pump assembly and the dialyser (<NUM>) one or more times so as to agitate a surface of the semi-permeable membrane of the dialyser (<NUM>), or
the control system is further operable to operate the outlet pump assembly in an outlet pump shuttling step additional to the inlet and outlet pump cycles to shuttle the second volume of dialysis fluid between the outlet pump assembly and the dialyser (<NUM> one or more times so as to agitate a surface of the semi-permeable membrane of the dialyser (<NUM>).