Assessing the integrity of forward osmosis membranes using transmembrane pressure difference.

Abstract

A control device (10) and method for assessing the integrity of a forward osmosis (FO) membrane (2c) of a FO device (2) in a dialysate generator (1), the FO membrane (2c) separating a feed side (2a, 2b) and a draw side (2a, 2b) of the FO device (2), the FO device (2) comprising a feed inlet port (Ein) and a feed outlet port (Eout) in fluid communication with the feed side (2a, 2b), and a draw inlet port (Lin) and a draw outlet port (Lout) in fluid communication with the draw side (2a, 2b). The method includes providing (S1) a flow of feed solution to the feed side (2a, 2b) through the feed inlet port (Ein) and providing (S2) a flow of draw solution to the draw side (2a, 2b) through the draw inlet port (Lin) at an osmotic pressure in the draw side (2a, 2b) that is higher than the osmotic pressure in the feed side (2a, 2b), whereby water is extracted from the feed side (2a, 2b) to the draw side (2a, 2b) and the draw solution is diluted. The method further includes stopping (S3) the flow through the draw inlet port (Lin), the feed inlet port (Ein), and the feed outlet port (Eout), whereby water continues to be extracted from the feed side (2a, 2b) to the draw side (2a, 2b) until a transmembrane pressure difference (TMP) between the draw side (2a, 2b) and the feed side (2a, 2b) reaches a maximum value. The method further includes monitoring one or more pressures indicative of the TMP (S4) and assessing the integrity of the FO membrane based on the one or more monitored parameters including the one or more pressures indicative of the TMP (S8).The present disclosure also relates to a solution generating device (1) for generating dialysis solution.

Description

[Technical field]

[0001] The present disclosure relates to the field of dialysis and to forward osmosis membrane integrity testing, and in particular to evaluating the integrity of forward osmosis membranes located in dialysate generators. [Background technology]

[0002] Dialysis is commonly used to treat patients with kidney failure. There are several types of dialysis treatments, such as hemodialysis (HD), peritoneal dialysis (PD) and continuous renal replacement therapy (CRRT). Typically, a dialysate is used in the treatment, which is either delivered pre-made in a bag or produced at the time of use by mixing a concentrate with water.

[0003] Forward osmosis (FO) has emerged as an option for producing dialysate because of its potential to reduce water consumption. FO membranes are typically designed to be more or less selective for water molecules, which allows them to separate water from all other contaminants. However, undetected integrity problems may allow the transport of components other than water across the FO membrane.

[0004] Therefore, there is a need to detect such integrity problems so that the produced dialysate is not compromised. Summary of the Invention

[0005] The FO membrane of the present disclosure is used to prepare a dialysis solution. The FO membrane, in one embodiment, is more or less selective for water molecules, which allows the FO membrane to separate water from all other contaminants. The osmotic pressure difference between the feed solution (e.g., water or effluent from a dialysis treatment) and the draw solution (dialysis concentrate), separated by the FO membrane, is used to extract pure water from the feed solution into the dialysis concentrate, thereby diluting the dialysis concentrate. The diluted dialysis concentrate is then used to produce the dialysis solution. The system and method of the present disclosure allow to detect integrity problems with the FO membrane and suppress changes in the composition of the produced dialysis solution due to the transport of components other than water across the FO membrane.

[0006] It is therefore an object of the present disclosure to provide a simple and reliable method for assessing the integrity of a forward osmosis membrane.A further object is to provide a method for assessing the integrity of a forward osmosis membrane online or during preparation of the dialysis fluid.

[0007] These and other objects are achieved at least in part by the methods, the control devices and the dialysate generating devices according to the independent claims and by the embodiments according to the dependent claims.

[0008] According to one aspect, which may be combined with any other aspects and embodiments thereof, the present disclosure relates to a method for evaluating the integrity of a forward osmosis (FO) membrane of a FO device in a dialysate generator. The FO membrane separates a feed side from a draw side of the FO device. The FO device comprises a feed inlet port and a feed outlet port in fluid communication with the feed side, and a draw inlet port and a draw outlet port in fluid communication with the draw side. The method includes providing a flow of a feed solution to the feed side through the feed inlet port, and providing a flow of a draw solution to the draw side through the draw inlet port at an osmotic pressure of the draw side higher than an osmotic pressure in the feed side, whereby water is extracted from the feed side to the draw side and the draw solution is diluted. The method further includes stopping the flow through the draw inlet port, the feed inlet port, and the feed outlet port, whereby water continues to be extracted from the feed side to the draw side until a transmembrane pressure difference (TMP) between the draw side and the feed side reaches a maximum value. The method further includes monitoring one or more pressures indicative of the TMP and assessing the integrity of the FO membrane based on the one or more monitored parameters including the one or more pressures indicative of the TMP.

[0009] The method provides a simple and reliable way to assess the integrity of an FO membrane. An integrity error may be detected based on one or more pressures indicative of the TMP. For an FO membrane with integrity, the maximum TMP is expected to remain more or less constant and decrease very slowly. For an FO membrane with integrity error, depending on the cause of the error, convective liquid transport from the draw side to the feed side or diffusive solute transport from the draw side to the feed side (with diffusive water transport from the draw side to the feed side) may occur. In either case, the hydrostatic pressure on the feed side increases, resulting in a decrease in the maximum TMP and / or a relatively fast decrease in TMP after the maximum TMP is reached. This behavior is used to assess the integrity of the FO membrane. The method is easy to implement as it uses features already present in the dialysis solution generator and may be performed automatically without human intervention.

[0010] According to some embodiments, assessing the integrity includes evaluating the TMP or one or more pressure characteristics indicative of the TMP, including one or more of the magnitude, time to maximum value, and / or relaxation, which may provide information regarding the integrity of the FO membrane.

[0011] According to some embodiments, the assessment of the integrity includes assessing relaxation of the TMP based on one or more monitored pressures indicative of the TMP. The assessment of relaxation allows for small integrity errors to be detected.

[0012] According to some embodiments, the method includes assessing the integrity of the FO membrane based on a magnitude of the relaxation rate of the TMP determined based on one or more monitored pressures indicative of the TMP. The magnitude assessment also allows for small integrity errors to be detected.

[0013] According to some embodiments, the method includes evaluating the integrity based on the achievement of one or more integrity criteria for the magnitude of the relaxation rate of the TMP. The evaluation of the integrity criteria allows the severity of an integrity error to be determined.

[0014] According to some embodiments, assessing the integrity of the FO membrane includes assessing the integrity based on one or more monitored parameters including one or more pressures indicative of the TMP during a period of time after the shutdown has occurred, where the one or more pressures should reflect any integrity errors during such period of time.

[0015] According to some embodiments, the maximum value of the TMP is characterized by the relaxation rate of the TMP at zero magnitude, where the maximum value of the TMP may be defined as the TMP at its maximum point after the flow is stopped.

[0016] According to some embodiments, the method includes determining a maximum value of the TMP based on one or more monitored pressures indicative of the TMP, controlling a flow of the solution through the feed inlet port or the feed outlet port such that the TMP corresponds to the determined maximum value of the TMP based on the one or more monitored pressures indicative of the TMP and the determined maximum value of the TMP, and monitoring one or more parameters indicative of a flow rate of the resulting flow of the solution. Here, an alternative method of assessing integrity is achieved.

[0017] According to some embodiments, controlling includes controlling a speed of a feed pump, monitoring includes monitoring a speed of the feed pump, and assessing the integrity includes assessing the integrity of the FO membrane based on the monitored speed of the feed pump. Thus, an easily accomplished method is provided since the speed of the feed pump is readily available in the controller.

[0018] According to some embodiments, the method includes evaluating the integrity based on the achievement of one or more integrity criteria of one or more parameters indicative of a flow rate of the resulting stream of the feed solution. The integrity criteria make it possible to determine the severity of an integrity error.

[0019] According to some embodiments, the draw outlet port is connected to a dilute concentrate container, and thus the draw side is connected to atmospheric or near atmospheric pressure, which is typically kept constant during the process.

[0020] According to some embodiments, the monitoring includes monitoring one or more pressures including a pressure indicative of a feed side pressure and / or includes monitoring one or more pressures including a pressure indicative of a draw side pressure. Thus, the TMP may be derived in a number of ways.

[0021] According to some embodiments, the method includes increasing the hydrostatic pressure at the feed side to be greater than the hydrostatic pressure at the draw side. The method then includes monitoring one or more pressures indicative of the TMP and evaluating the integrity of the FO membrane based on the monitored one or more parameters including the one or more pressures indicative of the TMP. Thus, by establishing a bulk pressure at the feed side, leaks that are only present at the feed side can be distinguished from those that are only present at the draw side.

[0022] According to a second aspect, which may be combined with any other aspect and its embodiments, the present disclosure relates to a control device for evaluating the integrity of a forward osmosis (FO) membrane of a FO device in a dialysate generator. The FO membrane separates a feed side and a draw side of the FO device. The FO device comprises a feed inlet port and a feed outlet port in fluid communication with the feed side, and a draw inlet port and a draw outlet port in fluid communication with the draw side. The control device comprises a feed pump configured to provide a flow of a feed solution to the feed side via the feed inlet port, and a draw pump configured to provide a flow of a draw solution to the draw side via the draw inlet port at an osmotic pressure of the draw side higher than an osmotic pressure in the feed side, thereby enabling extraction of water from the feed side to the draw side and diluting the draw solution. The control device also comprises one or more pressure sensors configured to measure one or more pressures indicative of a TMP between the draw side and the feed side, and a valve device configured to control one or more flows via the draw inlet port, the feed inlet port, or the feed outlet port. The controller is further configured to stop flow through the draw inlet port, the feed inlet port, and the feed outlet port using the feed pump, the draw pump, and the valve device, thereby allowing water to continue to be extracted from the feed side to the draw side until a transmembrane pressure (TMP) between the draw side and the feed side reaches a maximum value. The controller is further configured to monitor one or more pressures indicative of the TMP using one or more pressure sensors, and evaluate the integrity of the FO membrane based on the one or more monitored parameters including the one or more pressures indicative of the TMP.

[0023] According to some embodiments, the control device according to the second aspect is configured to carry out any one of the embodiments according to the first aspect.

[0024] According to a third aspect, which may be combined with any other aspect and its embodiments, the present disclosure relates to a solution generator for generating a dialysis solution, the apparatus comprising a forward osmosis device comprising a FO membrane separating a feed side and a draw side of the FO device, the apparatus further comprising a controller according to the second aspect.

[0025] According to a fourth aspect, the present disclosure relates to a computer program comprising instructions for causing a control device according to the second aspect to carry out a method according to the first aspect.

[0026] According to a fifth aspect, the present disclosure relates to a computer readable medium having stored thereon the computer program of the fourth aspect. [Brief description of the drawings]

[0027] [Figure 1] FIG. 1 is a schematic diagram of a FO device according to some embodiments of the present disclosure. [Diagram 2] FIG. 2 illustrates an example of a dialysate generating device according to some embodiments of the present disclosure. [Diagram 3] FIG. 3 illustrates a method for assessing the integrity of the FO membrane of a FO device according to some embodiments of the present disclosure. [Figure 4] FIG. 4 illustrates test results obtained from implementing the method shown in FIG. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0028] In the following description, a method for assessing the integrity of a forward osmosis (FO) membrane is described. The FO membrane is used in an FO device of a dialysate generator to generate dialysate, which is then used to generate dialysate. The dialysate may be used in PD, HD, CRRT, or any other dialysis therapy that uses dialysate as a treatment or substitution fluid (e.g., to dilute blood after filtration).

[0029] In particular, FO membranes are used to extract water from patient effluent, tap water, or other water sources into a dialysis concentrate to produce dialysate. Membrane integrity may be defined as the quality or state of an intact membrane in perfect condition. Thus, an FO membrane with integrity is intact and not damaged or impaired in any way. FO membranes experience compromised integrity, for example, due to manufacturing errors or wear. Compromised integrity may cause integrity problems such as leakage (solute transfer) or reduced selectivity, which causes an increase in the rate of diffusive solute transport (solute flux) through the FO membrane. Undetected integrity problems may change the composition of the produced dialysate by allowing transport of components other than water across the FO membrane. For example, leakage may allow transport of microorganisms from the feed side (effluent or tap water) to the draw side (mixed side), increasing the risk of peritonitis, for example, in PD cases. Additionally, leaks may allow transport of solutes (electrolytes, glucose, urea, etc.) from the feed side (effluent or tap water) to the draw side (mixed side), thereby altering the composition of the produced dialysate. Increased rates of diffusive electrolyte transport may also present a risk of solutes (electrolytes, glucose, urea, etc.) diffusing across the FO membrane in one or both directions at rates that significantly alter the composition of the produced dialysate. The effluent here may include patient effluent during PD and / or spent dialysate during HD or CRRT.

[0030] As described in this disclosure, it has been found that it is possible to detect such integrity problems by stopping flow to and from the FO device after the FO membrane is installed in a dialysis fluid generator and monitoring the resulting TMP or one or more pressures indicative of the resulting TMP. For example, characteristics such as magnitude, time to maximum, and / or relaxation may be investigated. Depending on the magnitude of the relaxation rate, an assessment of integrity may be made. In other embodiments, the TMP is controlled to a maximum TMP determined after flow is stopped, whereby an assessment of integrity may be made based on the flow rate obtained from, the speed of, or the power to the pump, which is controlled to maintain the TMP at the maximum TMP.

[0031] In general, diffusive transport of water and solutes is driven by the concentration difference of the solute, e.g., between the feed side and the draw side. Solute movement (caused by leakage) is driven by the transmembrane pressure difference (TMP), e.g., the pressure difference between the feed side and the draw side.

[0032] In some embodiments, the evaluation relies on existing technology and concentrates used to produce dialysate. For example, a pressure sensor already exists to sense the pressure on the feed side. The solution used is a solution already used to produce dialysate, for example, tap water, effluent from a dialysis treatment, or dialysis concentrate.

[0033] In the following, embodiments of the present disclosure will be described with reference to Figures 1 to 4. Figure 1 is a schematic diagram of a single FO device 2 according to some embodiments. The FO device 2 comprises a first side 2a and a second side 2b separated by a FO membrane 2c. For ease of illustration and description, the first side 2a on the left side will be referred to as the feed side and the second side 2b on the right side will be referred to as the draw side. However, depending on the direction of the osmotic pressure difference of the liquids flowing on both sides 2a, 2b, the first side 2a can also be referred to as the draw side and the second side 2b as the feed side. The sides may also be referred to herein as compartments or chambers. In use, the FO membrane 2c separates a solution on the feed side (referred to as the feed solution) from a solution on the draw side (referred to as the draw solution). Due to the osmotic pressure difference between the fluids, the draw solution on the draw side "draws" pure water from the feed solution on the feed side. Thus, water is extracted from the feed solution on the feed side 2a to the draw solution on the draw side 2b. As a result, in the FO process, the feed solution is dehydrated and the draw solution is diluted in the FO device 2. The FO membrane 2c is designed to be more or less selective for the permeating water molecules, which allows it to separate water from all other contaminants. The FO membrane 2c is therefore a water-permeable membrane. The FO membrane 2c typically has a pore size in the nanometer (nm) range, for example 0.5 to 5 nm or less, depending on the solutes that are intended to be blocked. The FO device 2 typically includes a feed side 2a, a draw side 2b, and a cartridge that surrounds the FO membrane 2c. The shape of the FO membrane 2c can be a flat sheet or tubular or hollow fiber. The feed side 2a is connected to an inlet port E through which the feed solution enters the feed side 2a. in and an outlet port E through which the feed solution exits the feed side 2a. out The draw side 2b has an inlet port L through which the draw solution enters the draw side 2b. in and the outlet port L through which the draw solution exits the draw side 2b. out Thus, the liquids on both sides typically flow countercurrently, but may alternatively flow cocurrently. The flow is continuous. A suitable FO device for the FO device 2 is, for example, the AquaporinTM , AsahiKASEI TM , Berghof TM , C.S.M. TM , FTSH2O TM , Koch Membrane Systems TM , Porifera TM , Toyoboshi TM and Toray TM may be provided by

[0034] The feed solution is, for example, the effluent from a current or previous dialysis treatment or water. In some embodiments, the effluent has an osmolality of about 8 bar (116 psig). Water typically has an osmolality well below 1 bar (14.5 psig). The draw solution is, for example, a dialysis concentrate, and the extracted water dilutes the dialysis concentrate to a dialysis solution, which may also be called a "diluted dialysis concentrate", "intermediate dialysis solution", or simply "dialysis solution". The dialysis concentrate is, for example, a concentrate that includes at least one of a plurality of NaCl, KCl, CaCl2, MgCl2, HAc, glucose, lactate, and bicarbonate. For example, the dialysis concentrate may include NaCl, CaCl2, MgCl2, and Na-lactate. Such a dialysis concentrate may have an osmolality of about 130 bar (1885 psig). A 50 percent glucose concentrate may have a pressure of about 70 bar (1015 psig). Other dialysis concentrates for HD may have an osmolality of 260 bar (3770 psig). Thus, the osmolality of the dialysate concentrate is typically greater than 50 bar (725 psig), for example, from 70 to 260 bar (1015 to 3770 psig), and in one embodiment, from 130 to 260 bar (1885 to 3770 psig).

[0035] FIG. 2 illustrates a dialysate generating apparatus 1 (hereinafter "apparatus 1") according to some embodiments of the present disclosure. Apparatus 1 includes a FO device 2 as described with reference to FIG. 1. Apparatus 1 also includes a flow path 20 including a number of liquid lines 20a-20n, hereinafter referred to as "lines." Apparatus 1 further includes a controller 30. Controller 30 includes a feed pump 3, a draw pump 5, and a diluted dialysis concentrate pump 6. Any of the pumps herein may be volumetric pumps (such as piston pumps) or non-volumetric pumps (e.g., gear pumps) with flow feedback, for example, from a flow sensor (not shown). Feed pump 3 is connected to an inlet connector P i The feed pump 3 is configured to pump effluent from a patient connected to the inlet connector P into the effluent container 35. Depending on the state of the valve, the feed pump 3 pumps effluent from the patient connected to the inlet connector P into the effluent container 35 or iThe draw pump 5 is configured to provide a flow of dialysis concentrate from the dialysis concentrate container 31 to the second side 2b and from the first side 2a to a drain (not shown). The draw pump 5 is configured to provide a flow of dialysis concentrate from the dialysis concentrate container 31 to the second side 2b depending on the state of the valve, and further to pump the solution produced on the second side 2b to the dilute concentrate container 32. The pure water container 33 contains pure water. The liquid container 34 contains an osmotic agent or buffer solution, e.g., glucose or bicarbonate. The apparatus 1 also comprises a conductivity sensor 7 configured to sense the conductivity of the solution produced from the second side 2b. The conductivity sensor 7 is configured to sense a conductivity in the range of 0.1 to 40 mS / cm. The conductivity sensor may also include a temperature sensor (not shown) for compensating the sensed conductivity value. The apparatus 1 further comprises one or more pressure sensors configured to sense a pressure indicative of a transmembrane pressure (TMP) of the FO device 2. For example, the apparatus 1 comprises a pressure sensor 8 arranged to sense the pressure of the feed side 2a. The apparatus 1 may comprise additional pressure sensors, for example arranged to sense the pressure of the draw side 2b. The dilute dialysis concentrate pump 6 is configured to provide a flow of liquid to the main line 20f. The controller 30 also comprises a valve arrangement 10 comprising a number of valves 10a-10m. In general, the valves connected to the lines can be configured to be open, where the flow of liquid in the line is permitted, and closed, where the flow of liquid in the line is stopped. The valves may be, for example, on / off valves, where the on state is the state when the flow of liquid in the line is permitted and the off state is the state when the flow of liquid in the line is stopped. The controller 30 further comprises a control unit 50 comprising at least one memory and at least one processor. The controller 30 is configured to control, via the control unit 50, the valves of the pump and valve arrangement 10 and the function of the mixing unit 9 to perform a number of different processes, such as diluting the dialysis concentrate into dialysis solution, delivering dialysis solution, and performing a cleaning or priming process. The controller 30 is also configured to receive conductivity measurements from the conductivity sensor 7.The controller 30 is further configured to receive pressure measurements from one or more pressure sensors, including the pressure sensor 8. Specifically, the controller 30 is configured to assess the integrity of the FO membrane 2c in the device 1, as defined by the method shown in FIG. 3. To that end, the at least one memory includes instructions for assessing the integrity of the FO membrane 2c. When the instructions are executed by the at least one processor, the controller 30 executes a method for assessing the integrity of the FO membrane 2c, which will be described below. The method may be executed by the controller 30 and stored as a computer program including computer instructions on the at least one memory.

[0036] First, however, the device 1 of FIG. 2 will be described in more detail. In FIG. 2, the inlet connector P i and feed inlet port E in A first effluent inlet line 20a is connected to an inlet connector P i and the feed inlet port E of the first side 2a in The inlet connector P ican be connected, for example, to the effluent line or catheter of a PD patient or to the used dialysate line of an HD or CRRT machine. A first effluent inlet valve 10a is connected to the first effluent inlet line 20a. A second effluent inlet line 20b is arranged between the first effluent inlet line 20a and the effluent container 35 to connect the first effluent inlet line 20a and the effluent container 35. A feed pump 3 is arranged to provide a flow of effluent in the second effluent inlet line 20b. A second effluent inlet valve 10b is connected to the second effluent inlet line 20b. A third effluent inlet line 20c is arranged between the first effluent inlet line 20a and the second effluent inlet line 20b to connect the first effluent inlet line 20a and the second effluent inlet line 20b. A third effluent inlet valve 10c is connected to the third effluent inlet line 20c. A fourth effluent inlet valve 10d is connected to the first effluent inlet line 20a between the junction of the second effluent inlet line 20b and the third effluent inlet line 20c and the first effluent inlet line 20a. The effluent can be collected in the effluent container 35 by opening the first effluent inlet valve 10a and the second effluent inlet valve 10b, closing the third effluent inlet valve 10c and the fourth effluent inlet valve 10d, and pumping the effluent into the container 35 using the feed pump 3. The effluent can then be pumped by the feed pump 3 from the effluent container 35 to the feed side 2a by opening the second effluent inlet valve 10b and the fourth effluent inlet valve 10d and closing the first effluent inlet valve 10a and the third effluent inlet valve 10c. Instead, the effluent flows through the first effluent inlet valve 10a and the third effluent inlet valve 10c by opening the first effluent inlet valve 10b and the fourth effluent inlet valve 10d, the first effluent inlet line 20a, the second effluent inlet line 20b and the third effluent inlet line 20c, and the inlet connector P i The discharge may be pumped directly to the first side 2a by pumping the discharge liquid with a feed pump 3 from the first side 2a.

[0037] The effluent outlet line 20d is connected to the feed outlet port E of the first side 2a. outand a drain (not shown), and a feed outlet port E of the first side 2a out to the drain. The effluent outlet valve 10e is connected to the effluent outlet line 20d. Thus, the FO device 2 has a feed inlet port E in fluid communication with the feed side 2a. in and feed outlet port E out Equipped with.

[0038] Further, the dialysis concentrate container 31 and the draw inlet port L of the draw side 2b in A dialysis concentrate line 20e is provided between the dialysis concentrate container 31 and the draw inlet port L of the draw side 2b to connect the in 3. A draw pump 5 is arranged to provide a flow to the dialysis concentrate line 20e. A main line 20f is arranged between the dialysis concentrate line 20e and the mixing unit 9 and connects the dialysis concentrate line 20e and the mixing unit 9. The mixing unit 9 includes a main pump for controlling the flow rate obtained in the line 20m downstream of the mixing unit 9, a liquid pump for providing a flow of, for example, glucose solution from the liquid container 34, a conductivity sensor, a heater and a mixing chamber (these features are not explicitly shown). The main line 20f is connected to the dialysis concentrate line 20e between the dialysis concentrate container 31 and the draw pump 5. A diluent concentrate container line 20g is arranged between the diluent concentrate container 32 and the main line 20f to connect the diluent concentrate container 32 and the main line 20f. A conductivity sensor 7 is connected to the diluent concentrate container line 20g to sense the conductivity of the diluent dialysis concentrate in the diluent concentrate container line 20g. The diluent concentrate container valve 10g is connected to the diluent concentrate container line 20g. The draw outlet port L of the draw side 2b out A first connection line 20h is connected to the draw outlet port L of the draw side 2b to connect the draw side 2b to the dilution concentrate container line 20g. out and dilute concentrate container line 20g. Thus, FO device 2 has a draw inlet port L in fluid communication with draw side 2b. in and draw outlet port L outThe dialysis concentrate device 2 comprises a first main valve 10h connected to the main line 20f between the connection point of the main line 20f and the dialysis concentrate line 20e and the connection point of the dilute concentrate container line 20g and the main line 20f. The dialysis concentrate container can be pumped from the dialysis concentrate container 31 through the draw side 2b to the dilute concentrate container 32 by pumping using the draw pump 5 and closing the dilute concentrate container valve 10g and the first main valve 10h. At the same time, the effluent can be pumped to the feed side 2a. Then, pure water is extracted from the effluent of the feed side 2a to the dialysis concentrate of the draw side 2b via osmotic pressure. Thus, the dialysis concentrate is diluted to form an intermediate dialysate and collected in the dilute concentrate container 32. This procedure can be called an FO session. Thus, the FO device 2 is configured to be used in an FO session for diluting the dialysis concentrate in the process of producing a dialysate.

[0039] A liquid line 20i is arranged between the liquid container 34 and the mixing unit 9 to connect the liquid container 34 and the mixing unit 9. A second main valve 10k is connected to the main line 20f between the diluted dialysis concentrate pump 6 and the mixing unit 9. A water line 20n is arranged between the pure water container 33 and the mixing unit 9 to connect the pure water container 33 and the mixing unit 9. A water line 20n is arranged between ... mixing unit 9 and the outlet connector P o To connect the mixing unit 9 and the outlet connector P, an outlet line of 20 m is provided. o The outlet connector P o may be connected, for example, to a catheter of a PD patient or to the dialysate line of an HD or CRRT machine. An outlet valve 10m is arranged to operate with the outlet line 20m.

[0040] To mix the dialysis fluid, the diluted dialysis concentrate in the diluted concentrate container 32 is pumped into the mixing unit 9 by opening the diluted concentrate container valve 10g, the second main valve 10k and the outlet valve 10m and pumping with the diluted dialysis concentrate pump 6. At the same time, an osmotic agent such as glucose or a buffer solution is pumped into the mixing unit 9 and pumped with a liquid solution pump (not shown). Pure water flows to the mixing unit 9 through a water line 20n. A main pump (not shown) provides a desired flow rate of the resulting dialysis fluid in line 20m downstream of the mixing unit 9. A conductivity sensor (not shown) in the mixing unit 9 measures the conductivity of the dialysis fluid obtained from the mixing unit 9. The diluted dialysis concentrate pump 6 and the liquid pump are controlled to achieve a specific speed to achieve a desired predetermined concentration of the resulting dialysis fluid based on the conductivity of the produced fluid, the conductivity of the diluted dialysis concentrate and the flow rate of the produced fluid. In the mixing unit 9, the diluted dialysis concentrate, the osmotic agent / buffer solution and the pure water are mixed and optionally heated in a mixing chamber (not shown) to form the dialysis solution. The dialysis solution is then delivered via the outlet line 20m to the outlet connector P o , and delivered to the desired destination (eg, a storage container or a dialysis machine).

[0041] Pure water typically has the quality of water for injection (WFI) or water for dialysis (WFD). WFI has a total organic carbon (TOC) of up to 500 ppg, a conductivity of less than 1.3 μS / cm at 25° C., and bacterial endotoxins of less than 0.25 EU / ml. WFD has colony forming units (CFU) of less than 100 CFU / ml and endotoxin units of less than 0.25 EU / mL. See, for example, ISO 26722:2009, ISO 22519:2019.

[0042] A method for assessing the integrity of an FO membrane is then described with reference to the flow chart of FIG. 3. The method is for example implemented by the control unit 50 of FIG. 2. The FO membrane is for example the FO membrane 2c of the FO device 2 in the apparatus 1 of FIG. 2. However, the method may also be used in other apparatuses equipped with an FO membrane for assessing its integrity. The method may be implemented before therapy is started or after therapy has stopped. The method may also be started while therapy is in progress. Then, the production of dialysate is interrupted while the method is being implemented. In one embodiment, the method includes: in The method includes providing a flow of the feed solution to the feed side 2a via the feed inlet port E1. In other words, the method includes passing the feed solution through the feed side 2a. Thus, the feed solution is passed through the feed inlet port E2. in Feed inlet port E is provided in From there, through the first side 2a for osmotic exchange, through the FO membrane 2c to the outlet port E out 3, where the solution exits the FO device 2. The feed solution may be, for example, effluent or water. If the feed solution is effluent, passing S1 uses the feed pump 3 and opens and closes the appropriate valves to feed the effluent container 35, the patient or the inlet connector P. i from another source fluidly connected to the inlet port E of the first side 2a. in If the feed solution is water, the method includes connecting a water source to a first effluent inlet line 20a, e.g., an inlet connector P i and pumping water into the feed side 2a with a feed pump 3. Providing S1 includes connecting the first side 2a to the outlet port E outand further pumping the feed solution from the feed pump 3 to a drain (not shown). The operating point of the device 1 is typically well defined while providing S1 a flow of the feed solution. For example, the operating point includes providing S1 a flow of the feed solution at a constant, relatively high flow rate of the feed solution provided to the feed side 2a. In the case of PD, the flow rate provided by the feed pump 3 is, for example, 50 to 200 ml / min. In the case of HD, the flow rate provided by the feed pump 3 is, for example, 200 to 600 ml / min. The flow rate is either directly controlled by the feed pump 3 or is measured by a flow sensor (not shown) and used as feedback for flow rate control in the feed pump 3. The operating point may also include providing S1 a hydrostatic pressure to the feed side 2a. The hydrostatic pressure may simply be the result of providing a certain flow rate, as described above. Alternatively, providing S1 includes controlling the hydrostatic pressure of the feed side 2a to a certain pressure, for example, near atmospheric pressure or atmospheric pressure. The pressure is controlled, for example, using the feed pump 3 and / or the valve 10e. The feed side pressure may be measured using a pressure sensor 8 and used as feedback for pressure control by the feed pump 3 and / or the effluent outlet valve 10e.

[0043] The method is to draw the inlet port L in Providing S2 a flow of draw solution to the draw side 2b via the draw inlet port L may be performed while providing S1 a flow of feed solution to the feed side 2a. In other words, the method includes passing draw solution to the second side 2b. Thus, the draw inlet port L in The draw solution provided to the draw inlet port L in From there, through the second side 2b for osmotic exchange, through the FO membrane 2c to the draw outlet port L out 2, where the solution exits the FO device 2. The draw solution is a dialysis concentrate, such as, for example, dialysis concentrate. In the case of dialysis concentrate, providing S2 now involves using the draw pump 5, closing the first main valve 10h and the diluent concentrate container valve 10g, and drawing water from the dialysis concentrate container 31 to the draw inlet port L of the second side 2b.in The method includes pumping the dialysis concentrate to the feed side 2b. The draw solution has a higher osmolality than the feed solution. Providing a draw solution stream S2 therefore includes providing a draw solution stream having an osmolality at the feed side 2b that is higher than the osmolality at the feed side 2a. This extracts water from the feed side 2a to the draw side 2b, diluting the draw solution. The method therefore includes diluting the draw solution and dehydrating the feed solution. The osmolality of a solution is proportional to the molar concentration of solute particles in the solution. The solute particles in question may be electrolytes. An electrolyte is a substance that conducts electricity when dissolved in water. In some embodiments, the draw solution has an osmolality between 70 and 260 bar (1015 and 3770 psig). The feed solution shall therefore have an osmolality of less than 70 bar (1015 psig), for example less than 10 bar (145 psig), to provide an osmolality difference between the feed side 2a and the draw side 2b. The effluent may have an osmotic pressure of about 8 bar (116 psig). Water has a very low osmotic pressure, typically much lower than 1 bar (14.5 psig). Thus, in some embodiments, the osmotic pressure at the draw side 2b is at least 60 bar (870 psig) higher than the osmotic pressure at the feed side 2a. The hydrostatic pressure at the draw side 2b may be close to atmospheric pressure. Thus, the hydrostatic pressures at the feed side 2a and the draw side 2b may be equal or close to equal in magnitude. The operating point of the apparatus 1 is typically well defined while providing a flow of draw solution S2. For example, the operating point includes providing a flow of draw solution S2 at a constant flow rate of the draw solution provided to the draw side 2b. The flow rate provided by the draw pump 5 is typically reduced via a dilution factor of the draw solution, e.g., 1:20. Thus, the flow provided by the draw pump 5 may be 20 times lower than the flow provided by the feed pump 3. The flow rate is either directly controlled at the draw pump 5 or is measured by a flow sensor (not shown) and used as feedback for flow rate control at the draw pump 5.

[0044] When flow is provided on both sides 2a, 2b, the method is to have flow through the draw inlet port Lin, the feed inlet port E in and the feed outlet port E out In the apparatus 1 shown in FIG. 2, this step includes stopping the flow through the draw inlet port L. in Stopping the draw pump 5 to stop flow through the feed inlet port E in and closing the fourth effluent inlet valve 10d and the third effluent inlet valve 10c (or the second effluent inlet valve 10b) to stop flow through the feed outlet port E. out and closing the drain outlet valve 10e to stop flow through the draw outlet port L. out is still fluidly connected to the diluent concentrate container 32. Thus, the draw outlet port L outLiquid is allowed through. When the flow is stopped in step S3, the hydrostatic pressure in the dilute concentrate vessel 32 is assumed to be close to atmospheric pressure, e.g., 1013 hPa (about 1 bar, 14.5 psig). Because the draw side 2b and the dilute concentrate vessel 32 are fluidly connected, they are also at approximately the same pressure, except for the hydrostatic pressure difference. However, in some embodiments, the method includes measuring the pressure at the draw side 2b to obtain the pressure at the draw side 2b. After the flow is stopped, water continues to be extracted from the feed side 2a to the draw side 2b until the transmembrane pressure difference (TMP) between the draw side 2b and the feed side 2a reaches a maximum value. At this time, the osmotic pressure difference between the feed side 2a, the draw side 2b and the TMP is in equilibrium. Thus, when the flow is stopped, there is no new feed solution entering the feed side 2a and no new draw solution entering the draw side 2b. However, the osmotic process continues. In this process, pure water moves through the FO membrane 2c from the feed side 2a to the draw side 2b, which reduces the hydrostatic pressure at the feed side 2a compared to the pressure when the process is stopped in step S3. The hydrostatic pressure at the draw side 2b remains more or less constant when connected to the dilute concentrate container 32. This is because the amount of water that can move from the feed side 2a to the draw side 2b is small compared to the volume of the dilute concentrate container 32. Thus, the TMP increases compared to the TMP when the flow is stopped in step S3. If there is a leak in the membrane, there may be solute movement from the draw side 2b to the feed side, but this flow is expected to be small compared to the main osmotic process with water molecules. The osmotic process continues until the TMP balances the osmotic pressure difference. Thus, the TMP is equal to the positive osmotic pressure difference (if TMP is defined as Pdraw-Pfeed). At this point, the TMP has reached its maximum value since the flow was stopped in step S3, and therefore the TMP has peaked. Here, the TMP changes from a negative TMP or zero TMP (when the flow is stopped) to a positive TMP. Thus, the TMP peak is a positive TMP peak. An example of a TMP curve with a TMP peak is shown in FIG. 4, which is explained below.At the maximum value of TMP, the rate of TMP is zero. Thus, the maximum value of TMP is also characterized by a relaxation rate of TMP with a magnitude of zero. In an ideal FO membrane 2 with integrity, the TMP remains fairly constant. However, most, if not all, FO membranes have a very small integrity error that is tolerated, which allows some solutes to diffuse from the draw side 2b to the feed side 2a, decreasing the TMP very slowly. Thus, the TMP begins to relax. The liquid in the FO unit 2 strives to maintain an equilibrium state between the osmotic pressure difference and the TMP. In an FO membrane with integrity error, the TMP is expected to decrease fairly rapidly after the TMP peaks. The rapid decrease is because a larger integrity error causes a larger diffusion of solutes or a leak flow from the draw side 2b to the feed side 2a. Thus, the progression of the TMP during the period after the TMP peaks can be used as a basis for evaluating the integrity of the FO membrane 2. To understand how the TMP progresses, the TMP needs to be monitored. Thus, the method includes monitoring S4 one or more pressures indicative of the TMP. For example, monitoring S4 includes monitoring the pressure at the feed side 2a using pressure sensor 8. Monitoring S4 includes repeatedly measuring the pressure at the feed side 2a. Monitoring S4 may include determining the TMP from the pressure measured at the feed side 2a, assuming that the pressure at the draw side 2b is constant and close to atmospheric pressure, e.g., less than 1 bar (14.5 psig). The TMP is often represented by the pressure measured at the feed side 2a, e.g., the pressure measured by pressure sensor 8. However, as the hydrostatic pressure at the feed side 2a decreases until it reaches a TMP peak, the TMP peak, and thus the maximum value of the TMP, corresponds to when the hydrostatic pressure at the feed side 2a reaches a minimum value. Alternatively, the method also includes measuring the hydrostatic pressure at the draw side 2b. Monitoring S4 then includes repeatedly measuring the pressure at the draw side 2b. The method may include determining the TMP as the hydrostatic pressure at the draw side 2b, Pdraw, minus the hydrostatic pressure at the feed side 2a, Pfeed.In other words, monitoring S4 includes monitoring one or more pressures including a pressure indicative of the pressure of the feed side 2a and / or includes monitoring one or more pressures including a pressure indicative of the pressure of the draw side 2b.

[0045] The TMP provides a basis for evaluating the integrity of the FO membrane. In a first embodiment, the method includes evaluating S8 the integrity of the FO membrane based on one or more pressures indicative of the TMP. Thus, the one or more parameters monitored include one or more pressures indicative of the TMP. The characteristics of the TMP provide a basis for evaluating the integrity of the FO membrane 2c. Thus, according to some embodiments, evaluating S8 the integrity includes evaluating a characteristic of the TMP or one or more pressures indicative of the TMP, including one or more of the magnitude, the time to reach a maximum value, and / or the relaxation. The evaluating S8 may be based on the achievement of one or more integrity criteria defined for the characteristics of the TMP, for example, for one or more of the magnitude, the time to reach a maximum value, and / or the relaxation. The magnitude of the TMP at its maximum value gives an indication of whether the FO membrane has an integrity error. Also, the time it takes to reach a maximum TMP after the flow is stopped indicates whether the FO membrane has an integrity error. During the establishment of the maximum TMP, the integrity error causes the transport of liquid from the draw side 2a to the feed side 2b, causing the maximum TMP to be reached faster and / or at a lower level than in the absence of the integrity error. Thus, evaluating the integrity S8 may include determining and comparing the magnitude of the TMP at its maximum value with a predefined magnitude of the TMP at its maximum value defined for an FO membrane having integrity (for a comparable liquid). Also, evaluating the integrity S8 may include determining the time required to establish the maximum TMP defined for an FO membrane having integrity and comparing the time required to establish the maximum TMP. If the difference is less than or equal to a predefined threshold, respectively, evaluating S8 may include determining that the FO membrane has sufficient integrity, otherwise determining that the FO membrane lacks sufficient integrity. The threshold value may be predetermined by experiment or calculation. After reaching the maximum TMP, the TMP aims to relax, so that if the FO filter has an integrity error, liquid can move from the draw side 2b, which has a higher hydrostatic pressure, to the feed side 2a, which has a lower hydrostatic pressure. The difference between the hydrostatic pressure of the feed side 2a and the hydrostatic pressure of the draw side 2b then decreases.This means that the TMP is reduced and therefore undergoes relaxation. In other words, assessing the completeness S8 includes assessing the relaxation of the TMP based on one or more monitored pressures indicative of the TMP. Thus, the method includes monitoring one or more pressures for relaxation. Because the pressures are not controlled, the relaxation may be referred to as free or uncontrolled pressure difference relaxation between the feed side 2a and the draw side 2b. The relaxation may be caused by either convective liquid transport from the draw side 2b to the feed side 2a, and thus leakage, or diffusive solute transport from the draw side 2b to the feed side 2a (diffusive water transport from the draw side 2b to the feed side 2a). The TMP relaxation rate and / or the properties of the TMP may be monitored. The greater the leakage and / or the diffusive transport, the greater the magnitude of the relaxation rate of the TMP. Thus, the relaxation rate is the time derivative or time gradient of the TMP. The relaxation rate indicates at what rate the TMP is being relaxed and therefore at what rate the hydrostatic pressures of the feed side 2a and the draw side 2b are being equalized. Thus, according to some embodiments, the method includes evaluating S8 the integrity of the FO membrane 2c based on the magnitude of the relaxation rate of the TMP determined based on the monitored one or more pressures indicative of the TMP. To evaluate the integrity of the FO membrane 2c, certain integrity criteria can be applied to the magnitude of the relaxation rate. The integrity criteria can include one or more predefined magnitude thresholds. By comparing the magnitude of the relaxation rate to one or more predefined magnitude thresholds, the integrity of the FO membrane can be established. The one or more thresholds are pre-determined, for example, by experiment or calculation. In some embodiments, a first predefined magnitude threshold defines a first upper limit of the size of the FO membrane 2c having integrity, which sets a limit of acceptable size. If the size is below the first upper limit or above the first upper limit, the evaluation includes determining that the FO membrane 2c has integrity. Thus, the relaxation rate is very slow, indicating normal FO membrane properties (no leaks and expected / allowable rate of solute diffusion). If the magnitude is above the first upper limit, the evaluation includes determining that the FO membrane 2c has an integrity error. In some embodiments, a second predetermined magnitude threshold defines a second upper limit for the magnitude of an intact FO membrane 2c.The second upper limit is greater than the first upper limit. If the magnitude is greater than the first upper limit but less than or greater than the second upper limit, the evaluation includes determining that the FO membrane 2c has a small integrity error. The relaxation rate is in the slow to moderate range, indicating an elevated electrolyte diffusion rate and / or a small membrane leak. If the magnitude is greater than the second upper limit, the evaluation includes determining that the FO membrane 2c has a large integrity error. The relaxation rate is then considered high, indicating a significant solute transfer of liquid from the draw side 2b to the feed side 2a and / or a membrane leak allowing a higher elevated rate of solute diffusion across the membrane. Thus, the method includes evaluating the integrity based on the achievement of one or more integrity criteria for the magnitude of the relaxation rate of the TMP S8. The relaxation rate may be determined for a period of time after the TMP peak, for example, the first 2 to 5 minutes after the TMP peak. In other words, according to some embodiments, assessing the integrity of the FO membrane includes assessing the integrity based on one or more monitored parameters including one or more pressures indicative of the TMP during a period of time after the maximum TMP is achieved. The results may be communicated to a user via a user interface (not shown) of the controller 10 and / or an alarm may be activated if an integrity error is detected. The user may then take appropriate action, such as replacing the FO device, if there is an integrity error.

[0046] Using the above method, tests were performed with an FO membrane with integrity (healthy FO membrane) and with the same FO membrane with one broken fiber (meaning a leak the size of the cross-sectional area of ​​two fibers). The tests were performed twice (N, M) with the same FO membrane. The FO membrane used contained aquaporins. TMThe model is Hollow Fiber Forward Osmosis 2 (HFFO2) manufactured by Eppendorf. The results are shown in Figure 4 with TMP (mmHg) on ​​the vertical axis and time (s) on the horizontal axis. The figure shows four TMP curves, two with an intact FO membrane and two with one broken fiber. An FO session was performed with a concentrate containing NaCl, CaCl2, MgCl2 and Na-lactate on the draw side (2.5 ml / min) (corresponding to step S1 of the method) and the same concentrate diluted 1:20 to mimic the PD effluent on the feed side (50 ml / min) (corresponding to step S2 of the method). The FO session was abruptly stopped at time t=0 (corresponding to step S3 of the method) by stopping the pump and closing the effluent outlet valve 10e. Pressures were measured on the feed and draw sides and TMP was calculated as TMP=Pdraw-Pfeed (corresponding to steps S4 and S8 of the method). The resulting TMP is shown in Figure 4, where M1 and N1 indicate the TMP peaks of the FO membrane with integrity, and M2 and N2 are for the single fiber breakage. Pdraw was almost constant as the draw side was open to the liquid collector bag. Pfeed dropped rapidly as water was transported from the feed side to the draw side by the remaining osmotic pressure difference, thereby raising the TMP. In the intact FO membrane test, the TMP rose to about 300 mmHg (M1 and N1) and then slowly dropped during the 35 min recording. When a single fiber was manually broken, the TMP dropped rapidly after an initial rise of about 300 mmHg (M2) and about 280 mmHg (N2) in two different tests. The results strongly support that small leaks significantly change the TMP relaxation rate and thus the method is sensitive enough for automated integrity assessment.

[0047] In a second embodiment, the method includes the following additional steps S5-S7 after step S4. In this embodiment, the second embodiment includes determining S5 a maximum value of the TMP based on one or more monitored pressures indicative of the TMP. The maximum value of the TMP corresponds to the TMP when it has a relaxation rate of zero magnitude after the flow is stopped in step S3. As explained, when the TMP is at its maximum value, the hydrostatic pressure at the feed side 2a is at its minimum value. Thus, the method may include determining as the maximum value of the TMP the TMP value having a relaxation rate of zero magnitude that occurs simultaneously when the hydrostatic pressure at the feed side 2a reaches its minimum value. The method includes determining as the maximum value of the TMP the TMP value having a relaxation rate of zero magnitude that occurs simultaneously when the hydrostatic pressure at the feed side 2a reaches its minimum value based on the one or more monitored pressures indicative of the TMP and the determined maximum value of the TMP, the feed inlet port E is opened so that the TMP corresponds to the determined maximum value of the TMP. in or feed outlet port E out In other words, the flow may be controlled, for example, through the feed inlet port E depending on which pump is used for control. in or feed outlet port E out or . The method includes comparing the TMP after the maximum TMP is achieved with the maximum determined TMP and eliminating the difference therebetween by controlling the flow rate of the feed solution. Thus, the method includes controlling the TMP to be equal to the determined maximum TMP. Controlling S6 is typically performed by controlling the speed of the pump. In the embodiment of FIG. 2, controlling S6 includes controlling the speed of the feed pump 3. If there is an integrity problem, it is expected that liquid will be transported from the draw side 2b to the feed side 2b, and then the TMP will decrease, as previously described. To maintain the TMP at the determined maximum TMP, the method controls the feed pump 3 to pump the liquid from the feed side 2a to the feed inlet port E to the drain container 35. in The drain outlet valve 10e remains closed. Instead, liquid is pumped from the feed side 2a to the feed outlet port E. outAnother pump (not shown) may be arranged to drain the solution through the drain outlet valve 10e. The effluent outlet valve 10e is then opened and the feed pump 3 remains stopped. The integrity assessment can be performed by monitoring the result of the control in step S6, such as a parameter that is the resulting flow rate, the resulting pump speed, or the resulting power to the pump. Thus, the method includes monitoring S7 one or more parameters indicative of the flow rate of the resulting stream of solution. In some embodiments, the monitoring S7 includes monitoring the speed of the feed pump 3. The pump speed is already available in the controller 10, since it is a control parameter of each pump. The resulting flow rate may be measured using a flow sensor (not shown) or may be provided as a control parameter in the controller 10. The power to the pump, and thus the power, current or voltage used by the pump, is also a control parameter available to the controller 10.

[0048] The method according to the second embodiment further comprises evaluating S8 the integrity of the FO membrane 2c based on one or more monitored parameters indicative of the flow rate of the resulting flow of the solution. Here, the evaluation is based on parameters such as the characteristics of the resulting flow of the feed solution, e.g. the resulting flow rate of the solution from the feed side, the speed of the pump, or the power used by the pump. To evaluate the integrity of the FO membrane 2c, a specific integrity criterion can be applied to the one or more monitored parameters. Thus, a specific integrity criterion can be used to determine the integrity of the FO membrane 2c from the one or more monitored parameters. The integrity criterion can include one or more predefined parameter thresholds. The integrity of the FO membrane can be established by comparing the parameter with the one or more predefined parameter thresholds. The one or more thresholds are predefined, e.g., by experiment or calculation. In some embodiments, a first predefined magnitude threshold defines a first upper limit of the parameter value of the FO membrane 2c having integrity. If the parameter value is equal to or less than the first upper limit, the evaluation comprises determining that the FO membrane 2c has integrity. For example, the FO membrane 2c has integrity when no liquid needs to be removed from the feed side 2a to control the TMP to the desired TMP. Here, the resulting flow rate, speed or power is zero or close to zero. If the parameter value exceeds a first upper limit, the evaluation includes determining that the FO membrane 2c has an integrity error. Thus, if one of the resulting flow rate, speed or power, respectively, exceeds its first upper limit, the method includes determining that the FO membrane 2c has an integrity error. As will be appreciated, a parameter of a particular type is compared to a threshold or limit of the same type. In some embodiments, a second predetermined magnitude threshold defines a second upper limit for the parameter value of the FO membrane 2c having integrity. The second upper limit is greater than the first upper limit. If the parameter value exceeds the second upper limit, the evaluation includes determining that the FO membrane 2c has a significant integrity error. One or more parameters may be monitored for a period of time after the TMP peak, for example, the first 2 to 5 minutes after the TMP peak.Thus, the method includes assessing S8 the integrity based on the achievement of one or more integrity criteria of one or more parameters indicative of the flow rate of the resultant stream of feed solution.

[0049] The tested direction of solute movement (leakage) in the above-mentioned alternative is from the draw side 2b to the feed side 2a, which is less interesting from a risk point of view than the opposite direction. Nevertheless, the assessment is appropriate for solute selectivity and leaks that allow leakage in both directions. However, solute movement from the feed side 2a to the draw side 2b is important, since it poses a risk of carrying, for example, the patient's effluent to the liquid production side, thereby altering the composition of the produced fluid. Due to the possibility that a leak may act as a backflow valve and allow leakage only in one direction, the above-mentioned alternative may be complemented with a method step for testing solute movement from the feed side 2a to the draw side 2b. To test solute movement from the feed side 2a to the draw side 2b, a bulk pressure difference (Pfeed>Pdraw) from the feed side 2a to the draw side 2b is established by controlling a feed side pump, for example the feed pump 3, while monitoring the feed side pressure with a pressure sensor 8 and monitoring the relaxation pressure. Thus, the method includes temporarily increasing S9 the hydrostatic pressure on the feed side 2a. The increasing is performed after the tested directions from the draw side 2b and the feed side 2a have been performed, and thus after step S8 has been reached. The temporal increase requires that the hydrostatic pressure on the feed side 2a is increased compared to the hydrostatic pressure on the draw side 2b. The TMP then first goes to zero and then increases in the opposite direction compared to the direction of the TMP at the maximum TMP previously described. When the feed side pressure rises to a certain level, for example 300 mmHg, the feed pump 3 is stopped (thereby discharging the feed inlet port E). in Step S10 is performed, which includes stopping the flow through the draw inlet port L. in Flow through and feed outlet port E outFlow through feed inlet port E is likewise stopped. Now the same steps S4 and S8, and possibly S4 to S8, are repeated so that the TMP gradient is evaluated or maintained by pumping in a TMP with a gradient magnitude of zero using feed pump 3, with the only difference being that the evaluation evaluates the integrity error caused by leakage from feed side 2a to draw side 2b. Thus, in some embodiments, the method includes (i) increasing the hydrostatic pressure at feed side 2a to be greater than the hydrostatic pressure at draw side 2b after performing step S8, (ii) removing the hydrostatic pressure at feed inlet port E from feed inlet port E, and (iii) removing the hydrostatic pressure at draw side 2b from feed inlet port E. in and (ii) repeating method steps S4 and S8, or S4 through S8.

[0050] The present disclosure also relates to a controller 10 for assessing the integrity of a forward osmosis (FO) membrane 2c of a FO device 2 in a dialysate generator 1. The FO membrane 2c separates a feed side 2a and a draw side 2b of the FO device 2. The controller 10 is connected to a feed inlet port E in and a feed pump 3 configured to provide a flow of the feed solution to the feed side 2a via a draw inlet port L at an osmotic pressure in the draw side 2b that is higher than the osmotic pressure in the feed side 2a. in and a draw pump 5 configured to provide a flow of draw solution to the draw side 2b via the feed side 2a, thereby allowing extraction of water from the feed side 2a to the draw side 2b to dilute the draw solution. The controller 10 also includes one or more pressure sensors 8 configured to measure one or more pressures indicative of the TMP between the draw side 2b and the feed side 2a, and a valve arrangement 20 configured to control one or more flows through the draw inlet port, the feed inlet port, or the feed outlet port. The controller 10 controls the feed pump 3, the draw pump 5, and the valve arrangement 10 to control the flow of water through the draw inlet port E, the feed inlet port E, or the feed outlet port. in Flow through the feed inlet port L in and the feed outlet port E outand thereby allowing water to continue to be extracted from the feed side 2a to the draw side 2b until a transmembrane pressure (TMP) between the draw side 2a and the feed side 2b reaches a maximum value. The controller 10 is further configured to monitor one or more pressures indicative of the TMP using the one or more pressure sensors 8, and to assess the integrity of the FO membrane based on the one or more monitored parameters including the one or more monitored pressures.

[0051] According to some embodiments, the control device 10 is configured to perform the method according to any one of the embodiments described herein.

[0052] While the present invention has been described in connection with what are presently considered to be the most practical and preferred embodiments, it is to be understood that the invention is not limited to the disclosed embodiment, but on the contrary, it is intended to cover various modifications and equivalent arrangements included within the scope of the appended claims.

Claims

1. A method for assessing the integrity of a forward osmosis (FO) membrane (2c) of a FO device (2) in a dialysate generator (1), the FO membrane (2c) separating a feed side (2a) and a draw side (2b) of the FO device (2), the FO device (2) comprising a feed inlet port (Ein) and a feed outlet port (Eout) in fluid communication with the feed side (2a), and a draw inlet port (Lin) and a draw outlet port (Lout) in fluid communication with the draw side (2b), the method comprising: providing a flow of feed solution to the feed side (2a) via the feed inlet port (Ein) (S1); providing (S2) a flow of draw solution to the draw side (2b) through the draw inlet port (Lin) at an osmotic pressure in the draw side (2b) that is higher than the osmotic pressure in the feed side (2a), whereby water is extracted from the feed side (2a) to the draw side (2b) and the draw solution is diluted; Stopping (S3) flow through the draw inlet port (Lin), the feed inlet port (Ein), and the feed outlet port (Eout); Thereby, water continues to be extracted from the feed side (2a) to the draw side (2b) until the transmembrane pressure (TMP) between the draw side (2b) and the feed side (2a) reaches a maximum value, monitoring (S4) one or more pressures indicative of said TMP; and evaluating (S8) the integrity of the FO membrane based on one or more monitored parameters including the one or more pressures indicative of the TMP.

2. 2. The method of claim 1, wherein said evaluating the completeness (S8) comprises: evaluating one or more characteristics of said TMP or one or more pressures indicative of said TMP, including one or more of magnitude, time to peak and / or relaxation.

3. 3. The method of claim 2, further comprising evaluating (S8) the integrity of the FO membrane (2c) based on a magnitude of a relaxation rate of the TMP determined based on the monitored one or more pressures indicative of the TMP.

4. 4. The method of claim 3, comprising evaluating (S8) the integrity based on achievement of one or more integrity criteria for the magnitude of the relaxation rate of the TMP.

5. 2. The method of claim 1, wherein assessing (S8) the integrity of the FO membrane includes assessing the integrity based on one or more monitored parameters including the one or more pressures indicative of the TMP during a period after the stopping (S3) occurs.

6. 2. The method of claim 1, wherein the maximum value of the TMP is characterized by a relaxation rate of the TMP having a magnitude of zero.

7. 2. The method of claim 1, comprising: determining (S5) the maximum value of the TMP based on the monitored one or more pressures indicative of the TMP; and controlling (S6) a flow of solution through the feed inlet port (Ein) or the feed outlet port (Eout) based on the monitored pressure or pressures indicative of the TMP and the determined maximum value of TMP such that the TMP corresponds to the determined maximum value of TMP; and monitoring (S7) one or more parameters indicative of a flow rate of the resulting stream of solution.

8. 8. The method of claim 7, The controlling (S6) includes controlling a speed of a feed pump (3); The monitoring (S7) includes monitoring the speed of the feed pump (3); The method, wherein assessing the integrity (S8) comprises assessing the integrity of the FO membrane (2c) based on the monitored speed of the feed pump (3).

9. 8. The method of claim 7, comprising evaluating (S8) the integrity based on achievement of one or more integrity criteria of the one or more parameters indicative of a flow rate of the resultant stream of feed solution.

10. 2. The method of claim 1, wherein the draw outlet port (Lout) is connected to a dilute concentrate container (32).

11. 2. The method of claim 1, wherein the monitoring (S4) comprises monitoring one or more pressures including a pressure indicative of the pressure on the feed side (2a) and / or monitoring one or more pressures including a pressure indicative of the pressure on the draw side (2b).

12. 2. The method according to claim 1, further comprising increasing (S9) the hydrostatic pressure at the feed side (2a) to be greater than the hydrostatic pressure at the draw side (2b) and ｉｎ ), monitoring one or more pressures indicative of the TMP (S4), and assessing the integrity of the FO membrane based on one or more monitored parameters including the one or more pressures indicative of the TMP (S8).

13. A control device (10) for assessing the integrity of a forward osmosis (FO) membrane (2c) of a FO device (2) in a dialysate generator (1), the FO membrane (2c) separating a feed side (2a) and a draw side (2b) of the FO device (2), the FO device (2) comprising a feed inlet port (Ein) and a feed outlet port (Eout) in fluid communication with the feed side (2a), and a draw inlet port (Lin) and a draw outlet port (Lout) in fluid communication with the draw side (2b), the control device (10) comprising: a feed pump (3) configured to provide a flow of a feed solution to the feed side (2a) via the feed inlet port (Ein); a draw pump (5) for providing a flow of draw solution to the draw side (2b) through the draw inlet port (Lin) at an osmotic pressure in the draw side (2b) higher than the osmotic pressure in the feed side (2a), thereby allowing extraction of water from the feed side (2a) to the draw side (2b) and diluting the draw solution; one or more pressure sensors (8) configured to measure one or more pressures indicative of a TMP between the draw side (2b) and the feed side (2a); a valve device (20) configured to control one or more flows through at least one of the draw inlet port, the feed inlet port, or the feed outlet port. The control device (10) stopping the flow through the draw inlet port (Ein), the flow through the feed inlet port (Lin) and the flow through the feed outlet port (Eout) using the feed pump (5), the draw pump (5) and the valve device (10), thereby allowing water to continue to be extracted from the feed side (2a) to the draw side (2b) until a transmembrane pressure (TMP) between the draw side (2a) and the feed side (2b) reaches a maximum value; monitoring one or more pressures indicative of the TMP using the one or more pressure sensors (8); A controller configured to assess the integrity of the FO membrane based on one or more monitored parameters including the one or more pressures indicative of the TMP.

14. A control device (10) according to claim 13, configured to carry out the method according to any one of claims 1 to 12.

15. 14. A solution generator (1) for generating a dialysis solution, the solution generator (1) comprising a forward osmosis (FO) device (2) including an FO membrane (2c) separating a feed side (2a) and a draw side (2b) of the FO device (2), the solution generator further comprising a controller (10) according to claim 13.

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