Assessment of forward osmosis membrane integrity in continuous flow.

Abstract

A controller (10), a solution generator (1) and 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 device (2) is configured for use in an FO session for diluting a dialysis concentrate in a process for generating dialysate. The FO membrane (2c) separates a first side (2a) of the FO device (2) from a second side (2b). The method includes passing (S1) an electrolyte solution through the first side (2a) and passing (S2) a low electrolyte solution through the second side (2b). The method further comprises measuring (S3) the conductivity of the solution produced from the second side (2b) and assessing (S6) the integrity of the FO membrane (2c) based on whether the measured conductivity satisfies a conductivity criterion, the conductivity criterion comprising or defining the conductivity of a solution produced from the second side (2b) using an intact or intact FO membrane with an equivalent electrolyte solution and an equivalent low electrolyte solution.

Description

[Technical Field]

[0001] The present disclosure relates to the field of dialysis and to forward osmosis membrane integrity testing, and more particularly to assessing 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, including hemodialysis (HD), peritoneal dialysis (PD), and continuous renal replacement therapy (CRRT). Typically, a dialysate is used in the treatment, which is either delivered pre-formed in a bag or generated at the time of use by mixing a concentrate with water.

[0003] Forward osmosis (FO) has emerged as an option for producing dialysate due to its potential for reducing water consumption. FO membranes are typically designed to be more or less selective for water molecules, allowing them to separate water from all other contaminants. However, undetected integrity problems can 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 disclosed FO membrane is used to prepare dialysate. In one embodiment, the FO membrane is more or less selective for water molecules, allowing it to separate water from all other contaminants. The osmotic pressure difference between the feed (e.g., water or effluent from a dialysis treatment) and the draw (dialysis concentrate) separated by the FO membrane is used to extract pure water from the feed into the dialysis concentrate, thereby diluting the dialysis concentrate. The diluted dialysis concentrate is then used to produce dialysate. The disclosed control device and method enable detection of FO membrane integrity problems and suppression of changes in the composition of the dialysate caused by 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 forward osmosis membranes. A further object is to provide a method for assessing the integrity of forward osmosis membranes online or during preparation of dialysate.

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

[0008] According to a first aspect that can be combined with any other aspect and its embodiments, the present disclosure relates to a method for assessing the integrity of a forward osmosis (FO) membrane of a FO device in a dialysate generator. The FO device is configured for use in an FO session for diluting a dialysis concentrate in a process for producing dialysate. The FO membrane separates a first side of the FO device from a second side. The method includes passing an electrolyte solution through the first side of the FO membrane and a low-electrolyte solution through the second side of the FO membrane. The method further includes measuring the conductivity of a solution produced from the second side and assessing the integrity of the FO membrane based on whether the measured conductivity satisfies a conductivity standard, where the conductivity standard includes or defines the conductivity of a solution produced from the second side using an intact or intact FO membrane with an equivalent electrolyte solution and an equivalent low-electrolyte solution.

[0009] The provided method assesses the integrity of an FO membrane in a simple and reliable manner by evaluating how the conductivity of a solution produced from the second side corresponds to the expected conductivity of a solution produced from the second side using an FO membrane with comparable, and therefore identical, solutions and integrity. The method may be performed using the same equipment in which the FO membrane is installed for use, thereby allowing the integrity of the FO membrane to be tested almost always with the same equipment, and therefore online. Also, the same liquids may be used in the method as those later used for production.

[0010] According to some embodiments, assessing the integrity includes determining a lack of integrity of the FO membrane when the measured conductivity indicates a change in conductivity greater than a threshold value from the conductivity of the low electrolyte solution. Thus, by using the conductivity of the low electrolyte solution as a baseline, a sound integrity test can be performed.

[0011] According to some embodiments, the threshold value is based on the conductivity of the low electrolyte solution and a predetermined dilution ratio of the low electrolyte solution in the FO device, and thus the threshold value is based on the expected solute diffusion across the FO membrane.

[0012] According to some embodiments, the method includes passing an electrolyte solution through the first side at a hydrostatic pressure lower than the hydrostatic pressure on the second side, thereby disabling solute transfer from the first side to the second side, whereby a determined lack of integrity of the FO membrane indicates a solute diffusion error in the FO membrane, which may further identify the cause of the integrity error.

[0013] According to some embodiments, the method includes passing an electrolyte solution through a first side at a hydrostatic pressure greater than the hydrostatic pressure on the second side, measuring the conductivity of the solution produced from the second side, and determining that a lack of integrity of the FO membrane indicates a leak in the FO membrane when the measured conductivity exhibits a conductivity change greater than the conductivity change detected at the first side at the lower hydrostatic pressure, thereby further identifying one or more causes of the integrity error.

[0014] According to some embodiments, the method includes passing a low-electrolyte solution through the second side at an osmotic pressure higher than that of the first side, which allows diffusive water transport from the first side to the second side. Thus, the osmotic pressure difference between the two sides can mimic actual conditions during dialysate production, allowing for integrity testing under more realistic conditions.

[0015] According to some embodiments, the method includes passing a low electrolyte solution through the second side at an osmotic pressure lower than that of the first side, which allows diffusive water transport from the second side to the first side. Thus, a low electrolyte solution such as water, which is a cheaper solution than other low electrolyte solutions such as glucose, can be used.

[0016] According to some embodiments, the low electrolyte solution is a glucose solution, thus using a readily available solution with a conductivity close to zero, so that any electrolyte solution that mixes with the low electrolyte solution is easily detected by conductivity sensing.

[0017] According to some embodiments, the low electrolyte solution is water, thus using a readily available, low-cost liquid with low conductivity, such that any electrolyte solution that mixes with the low electrolyte solution is easily detected by conductivity sensing.

[0018] According to some embodiments, the electrolyte solution is the effluent from a dialysis treatment, and therefore, a readily available electrolyte solution may be used.

[0019] According to some embodiments, the electrolyte solution is a diluted electrolyte concentrate, so that readily available electrolyte solutions can be used.

[0020] According to some embodiments, the low electrolyte solution has a conductivity in the range of 0 to 0.5 mS / cm, and in one embodiment has a conductivity of less than 0.1 mS / cm, so that any electrolyte solution that mixes with the low electrolyte solution is easily detected by conductivity sensing.

[0021] According to a second aspect, which can be combined with any other aspect and its embodiments, the present disclosure relates to a control device for evaluating the integrity of an FO membrane of a forward osmosis (FO) device in a dialysate generating apparatus. The FO device is configured to be used in an FO session for diluting a dialysis concentrate in a process of generating dialysate, and the FO membrane separates a first side of the FO device from a second side. The control device includes an evacuation pump configured to provide a flow of an electrolyte solution, a concentrate pump configured to provide a flow of a low-electrolyte solution, and a conductivity sensor configured to sense the conductivity of a solution generated from the second side. The control device is configured to pass the electrolyte solution through the first side using the evacuation pump and pass the low-electrolyte solution through the second side using the concentrate pump. The control device is further configured to measure the conductivity of the solution generated from the second side using the conductivity sensor. The controller is further configured to evaluate the integrity of the FO membrane based on whether the measured conductivity meets a conductivity criterion, the conductivity criterion including or defining the conductivity of a solution produced from the second side using an intact or intact FO membrane with an equivalent electrolyte solution and an equivalent low-electrolyte solution.

[0022] According to some embodiments, the control device is configured to perform any embodiment described herein according to the first aspect.

[0023] According to a third aspect, which may be combined with any other aspect and its embodiments, the present disclosure relates to a solution generating apparatus for generating a dialysis solution, the apparatus comprising a FO device comprising a FO membrane separating a first side from a second side of a forward osmosis device, the apparatus further comprising a control device according to the second aspect.

[0024] 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 perform a method according to the first aspect.

[0025] 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 explanation of the drawings]

[0026] [Figure 1] FIG. 1 is a schematic diagram of a FO device according to some embodiments of the present disclosure. [Figure 2] FIG. 2 illustrates an example of a dialysate generator according to some embodiments of the present disclosure. [Figure 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 the implementation of the method shown in FIG. DETAILED DESCRIPTION OF THE INVENTION

[0027] The following describes a method for assessing the integrity of a forward osmosis (FO) membrane. The FO membrane is used in an FO device in a dialysate generator to generate dialysate, which is then used to generate dialysate. Membrane integrity can 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 can experience compromised integrity due to, for example, manufacturing errors or wear. Compromised integrity can result in integrity issues such as leakage (solute migration) or reduced selectivity, which can lead to increased rates of diffusive solute transport (solute flux) through the FO membrane. Undetected integrity issues can alter the composition of the generated dialysate by allowing the transport of components other than water across the FO membrane. For example, leakage can allow the transport of microorganisms from the supply side (effluent or tap water) to the draw side (mixing side), increasing the risk of peritonitis, for example, in PD. Additionally, leaks can allow transport of solutes (electrolytes, glucose, urea, etc.) from the supply side (effluent or tap water) to the draw side (mixed side), thereby altering the composition of the produced dialysate. Also, increased rates of diffusive electrolyte transport can 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.

[0028] As described in this disclosure, it has been found that by using appropriate feed and draw solutions and by measuring the conductivity of the resulting solution, it is possible to detect such integrity problems after the FO membrane is installed in a dialysis fluid generator. Depending on which solution is used, the side usually referred to as the draw side may instead be the feed side. Therefore, hereinafter, both sides of the FO device are referred to as the first and second sides, and the resulting solution is the solution produced from the second side. By having a low electrolyte solution on the second side, small leaks or small rising rates of diffusive solute transport to the second side can also be detected by measuring the conductivity of the resulting solution, in order to predetermine what conductivity the resulting solution should have using an FO membrane with integrity under the same operating conditions. Convective fluid flow from the first side to the second side (flow from the feed side to the draw side during production) is important because it poses the risk of, for example, transporting patient effluent to the fluid production side, thereby changing the composition of the resulting fluid. Convective fluid flow in the opposite direction is less important because it does not change the composition of the resulting fluid. Due to the possibility that a leak may act as a backflow valve and only allow leakage in one direction, it is desirable for the leak detection method to test for leaks in the direction of most concern (from the supply side to the withdrawal side). Therefore, the conductivity of the solution produced from the second side is tested here.

[0029] In general, diffusive transport of water and solutes is driven by the solute concentration difference, i.e., the concentration difference between the first and second sides. Solute movement (caused by leakage) is driven by the transmembrane pressure (TMP), i.e., the pressure difference between the first and second sides.

[0030] In some embodiments, the evaluation relies on existing technology and concentrates used to generate dialysate. For example, a conductivity sensor already exists for sensing the conductivity of the solution generated from the second side during dialysate generation, and that same sensor can be used for this evaluation. The solution passing through the second side is, for example, a glucose solution or pure water already connected to the dialysate generator. The solution on the first side can be, for example, a effluent from a dialysis treatment that may be readily available in an effluent container, or it can be collected directly from the patient during normal dialysis treatment. Alternatively, the solution on the first side is a diluted electrolyte solution, also known as a buffer solution. The diluted electrolyte solution can then be diluted to an osmolality substantially below the osmolality of the solution on the second side.

[0031] Embodiments of the present disclosure will now be described with reference to FIGS. 1 to 4. FIG. 1 is a schematic diagram of a single FO device 2 according to some embodiments. The FO device 2 includes a first side 2a, e.g., a feed side, and a second side 2b, e.g., an outlet side, separated by an FO membrane 2c. The sides may also be referred to herein as compartments or chambers. The FO device 2 typically includes a cartridge enclosing the first side 2a, the second side 2b, and the FO membrane 2c. The FO membrane 2c may be in the form of a flat sheet, a tubular membrane, or a hollow fiber. The FO membrane 2c is a water-permeable membrane. The FO membrane 2c is designed to be more or less selective for permeating water molecules, allowing the FO membrane 2c to separate water from all other contaminants. The FO membrane 2c typically has a pore size in the nanometer (nm) range, e.g., 0.5 to 5 nm or less, depending on the solutes intended to be blocked. In use, the FO membrane 2c separates a solution on a supply side (typically a feed solution) from a solution on a second side (typically a draw solution). The liquids on these two sides typically flow countercurrently, but may alternatively flow cocurrently. In one embodiment, the flow is continuous, so that the flow is uninterrupted. The first side 2a has an inlet port E through which the solution enters the first side 2a. in and an outlet port E through which the solution exits from the first side 2a. outThe second side 2b has an inlet port L through which other solutions enter the second side 2b. in and an outlet port L through which the other solution exits from the second side 2b. out One solution is dehydrated, and the other solution is diluted according to the osmotic pressure difference between the solutions. TM , AsahiKASEI TM , Berghof TM , CSM TM , FTSH2O TM , Koch Membrane Systems TM , Porifera TM , Toyobo TM and Toray TM may be provided by

[0032] To produce the dialysate, water is extracted from the feed solution on the first side 2a to the draw solution on the second side 2b by osmotic pressure differential. The feed solution can be, for example, water or an effluent. In some embodiments, the effluent has an osmotic pressure of about 8 bar (116 psig). The draw solution can be, for example, a dialysis concentrate, and the extracted water dilutes the dialysis concentrate to a dialysate, which can also be referred to as a "diluted dialysis concentrate," an "intermediate dialysis solution," or simply "dialysate." In this disclosure, the dialysis concentrate can be referred to as an electrolyte solution, and the diluted dialysis concentrate can be referred to as a diluted electrolyte solution. The dialysis concentrate can be, for example, a concentrate containing at least one of NaCl, KCl, CaCl, MgCl, HAc, glucose, lactate, and bicarbonate. For example, the dialysis concentrate can contain NaCl, CaCl, MgCl, and Na-lactate.

[0033] In some embodiments, the dialysis concentrate has an osmolality of about 70 bar (1015 psig). The dialysate may be used for PD, HD, CRRT, or any other dialysis therapy that uses dialysate as a treatment or substitution fluid (e.g., to dilute blood after filtration).

[0034] In the present disclosure, an electrolyte solution is a solution with a sufficiently high concentration of electrolyte to result in a significant conductivity response on the second side if the integrity of the FO membrane is compromised. For example, the electrolyte concentration is 300 to 500 millimolar (mM), which is at least 20 times greater than the concentration of electrolyte in a low-electrolyte solution. Such an electrolyte solution may be, for example, a dilute electrolyte solution or effluent from a dialysis treatment. The effluent may include patient effluent during PD and / or used dialysate during HD. A low-electrolyte solution is a solution with a very low concentration of electrolyte. In some embodiments, the low-electrolyte solution has a conductivity in the range of 0 to 0.5 mS / cm, and in one embodiment, less than 0.1 mS / cm. Thus, the conductivity of a low-electrolyte solution is very low. A low-electrolyte solution may be, for example, a glucose solution or pure water.

[0035] Pure water is typically of water for injection (WFI) or water for dialysis (WFD) quality. WFI has a maximum of 500 ppg total organic carbon (TOC), a conductivity of less than 1.3 μS / cm at 25° C., and less than 0.25 EU / ml bacterial endotoxins. WFD has less than 100 CFU / ml colony-forming units (CFU) and less than 0.25 EU / mL endotoxin units. See, for example, ISO 26722:2009 and ISO 22519:2019.

[0036] 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 plurality of fluid lines 20a-20n, hereinafter referred to as "lines." Apparatus 1 further includes a controller 30. Controller 30 includes an effluent pump 3, a drain pump 4, a concentrate pump 5, and a dilute electrolyte 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 rate feedback from, for example, a flow sensor (not shown). Effluent pump 3 is configured to pump effluent from the patient into effluent container 35 depending on the state of the valves. Effluent pump 3 pumps effluent from the patient into either effluent container 35 or inlet connector P depending on the state of the valves. iThe controller 30 also includes a conductivity sensor 7 configured to sense the conductivity of the solution produced from the second side 2b. In one embodiment, the conductivity sensor 7 is configured to sense a conductivity in the range of 0.01 to 40 mS / cm. The conductivity sensor may also include a temperature sensor (not shown) for compensating the sensed conductivity value. The dilute electrolyte pump 6 is configured to provide a liquid flow to the main line 20f depending on the state of the valves. The dilute electrolyte pump 6 is configured to provide a liquid flow from, for example, a pure water container 33 or a liquid container 34 to the conductivity sensor 7 via line 20g. This is done so that the baseline conductivity of the low-electrolyte solution can be measured. The controller 30 also includes a valve device 10 including multiple valves 10a-10m. Generally, the valves connected to the lines can be configured to be open, allowing liquid flow through the line, or closed, stopping liquid flow through the line. The valves may be, for example, on / off valves, where the on state defines when liquid flow through the line is allowed and the off state defines when liquid flow through the line is stopped. The controller 30 further includes a control unit 50 including at least one memory and at least one processor. The controller 30 is configured to control the pumps 3-6 and the valves 10a-10m of the valve device 10 to perform multiple different processes, such as providing dialysis fluid, performing a cleaning process, or a 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 the pressure sensor 8. Specifically, the controller 30 is configured to assess the integrity of the FO membrane 2c in the apparatus 1 according to the method shown in FIG.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 performs a method for assessing the integrity of the FO membrane 2c, which is 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.

[0037] First, however, the device 1 of Figure 2 will be described in more detail. In Figure 2, the inlet connector P i and inlet port E in A first effluent inlet line 20a is connected to the inlet connector P i and the inlet port E of the first side 2a in The inlet connector P ican be connected to, for example, a catheter of a PD patient or the effluent line of an HD or CRRT device. 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. An effluent 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 second effluent inlet line 20b and the third effluent inlet line 20c. 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 effluent pump 3. The effluent can then be pumped by the effluent pump 3 from the effluent container 35 to the first 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 first effluent inlet valve 10a and the third effluent inlet valve 10c are opened, the second effluent inlet valve 10b and the fourth effluent inlet valve 10d are closed, and the effluent flows through the first effluent inlet line 20a, the second effluent inlet line 20b and the third effluent inlet line 20c to the inlet connector P i The effluent may be pumped directly to the first side 2a by pumping the effluent from the first effluent inlet line 20a with the effluent pump 3. A pressure sensor 8 is arranged to sense the pressure in the first effluent inlet line 20a. The pressure sensed by the pressure sensor 8 represents the pressure on the first side 2a.

[0038] The effluent outlet line 20d is connected to the outlet connector E on the first side 2a. outand the drain, and the outlet connector E of the first side 2a out to the drain. An effluent outlet valve 10e is connected to the effluent outlet line 20d. A drain pump 4 is arranged to provide flow to the effluent outlet line 20d and to control the hydrostatic pressure on the first side 2a. The effluent is pumped through the outlet connector E by opening the effluent outlet valve 10e and pumping with the drain pump 4. out The drain pump 4 may pump the effluent from the first side 2a to the drain. The effluent pump 3 and the drain pump 4 can therefore jointly pump to provide a desired flow rate of the effluent at the first side 2a at a desired hydrostatic pressure. The pressure at the first side 2a is measured by a pressure sensor 8, and the speed of the drain pump 4 is controlled to achieve the desired hydrostatic pressure at the first side 2a based on the pressure measured by the pressure sensor 8. The pressure at the second side 2b is assumed to be constant and close to atmospheric pressure, e.g., 1013 hPa. In some embodiments, the pressure at the second side 2b is measured by a separate pressure sensor (not shown). Alternatively, only the drain pump 4 is used to provide the effluent flow at the first side 2a. The second effluent inlet valve 10b, the third effluent inlet valve 10c, and the effluent outlet valve 10e are then opened, the effluent pump 3 is stopped, and the fourth effluent inlet valve 10d is closed.

[0039] Also, the electrolyte solution container 31 and the inlet port L of the second side 2b in An electrolyte solution line 20e is connected between the electrolyte solution container 31 and the inlet port L of the second side 2b to connect the inAn electrolyte solution valve 10f is connected to the electrolyte solution line 20e. A concentrate pump 5 is arranged to provide flow to the electrolyte solution line 20e. A main line 20f is arranged between the electrolyte solution line 20e and the mixing unit 9, connecting the electrolyte solution line 20e and the mixing unit 9. The mixing unit 9 includes liquid mixing functions such as a main pump that controls the flow rate obtained in line 20m downstream of the mixing unit 9, a low electrolyte solution pump that provides the flow of low electrolyte solution, a conductivity sensor, a heater, and a mixing chamber (these features are not explicitly shown). The main line 20f is connected to the electrolyte solution line 20e between the electrolyte solution valve 10f and the concentrate pump 5. A dilute electrolyte container line 20g is arranged between the dilute electrolyte container 32 and the main line 20f to connect the dilute electrolyte container 32 and the main line 20f. The dilute electrolyte container 32 is used to accumulate the electrolyte solution after it has been diluted in the FO session. A conductivity sensor 7 is connected to the diluted electrolyte container line 20g for sensing the conductivity of the liquid in the diluted electrolyte container line 20g. A diluted electrolyte container valve 10g is connected to the diluted electrolyte container line 20g. An outlet port L of the second side 2b out A first connecting line 20h is connected to the outlet port L of the second side 2b to connect the diluted electrolyte container line 20g to the outand the diluted electrolyte container line 20g. A first main valve 10h is connected to the main line 20f between the junction of the main line 20f and the electrolyte solution line 20e and the junction of the diluted electrolyte container line 20g and the main line 20f. By opening the electrolyte solution valve 10f, pumping using the concentrate pump 5, and closing the diluted electrolyte container valve 10g and the first main valve 10h, electrolyte solution can be pumped from the electrolyte container 31 to the diluted electrolyte container 32 via the second side 2b. At the same time, effluent can be passed through, i.e., pumped into, the first side 2a. Pure water is then extracted from the effluent on the first side 2a into the electrolyte solution on the second side 2b by osmotic pressure. Thus, the electrolyte solution is diluted to form an intermediate dialysate, which is collected in the diluted electrolyte container 32. This procedure can be referred to as a FO session. Thus, the FO device 2 is configured to be used in a FO session to dilute a dialysis concentrate (electrolyte solution) in the process of producing dialysate.

[0040] A third connection line 20p is arranged between the diluted electrolyte container line 20g and the third effluent inlet liquid line 20c, connecting the diluted electrolyte container line 20g and the third effluent inlet liquid line 20c. The third connection line 20p is connected to the diluted electrolyte container line 20g between the conductivity sensor 7 and the diluted electrolyte container valve 10g. The third connection line 20p is connected to the third effluent inlet liquid line 20c between the third effluent inlet valve 10c and its connection to the first effluent inlet line 20a. A valve 10p is connected to the third connection line 20p. 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 solution valve 10i is connected to the liquid line 20i. A second connection line 20j is arranged between the liquid line 20i and the main line 20f to connect the liquid line 20i and the main line 20f. The three-way valve 10j is connected to the second connection line 20j. A middle line 20k is arranged between the three-way valve 10j and the main liquid line 20f, connecting the three-way valve 10j and the main liquid line 20f. A second main valve 10k is connected to the main line 20f between the diluted electrolyte solution 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 ... o To connect the mixing unit 9 and the outlet connector P, a 20m outlet line is o The outlet connector P o may be connected, for example, to the catheter of a PD patient or to the dialysate line of an HD or CRRT machine. An outlet valve 10m is arranged in the outlet line 20m.

[0041] To mix the dialysate, the dilute electrolyte solution in the dilute electrolyte container 32 is pumped into the mixing unit 9 by opening the dilute electrolyte container valve 10g, the second main valve 10k, and the outlet valve 10m and pumping using the dilute electrolyte pump 6. Simultaneously, a low electrolyte solution, such as glucose, is pumped into the mixing unit 9 by opening the solution valve 10i and pumping using the low electrolyte solution pump (not shown). Pure water flows to the mixing unit 9 through the water line 20n. The main pump (not shown) provides the desired flow rate of the resulting dialysate in line 20m downstream of the mixing unit 9. A conductivity sensor (not shown) in the mixing unit 9 measures the conductivity of the dialysate obtained from the mixing unit 9. The dilute electrolyte pump 6 and the low electrolyte solution pump are controlled to specific speeds to achieve a predetermined desired concentration of the resulting dialysate based on the conductivity of the produced liquid, the conductivity of the diluted electrolyte solution, and the flow rate of the produced liquid. In the mixing unit 9, the dilute electrolyte solution, the low electrolyte solution, and the pure water are mixed in the mixing chamber to form the dialysate, which may optionally be heated. The dialysate then flows through a 20m outlet line to the outlet connector P o , and delivered to the desired destination (e.g., a storage container or a dialysis machine).

[0042] A method for assessing the integrity of an FO membrane is now described with reference to the flowchart of FIG. 3 . This method is implemented, for example, 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 . This method can be implemented before therapy is initiated, after therapy is stopped, or both. In some embodiments, the method includes measuring the conductivity of the low electrolyte solution (S0). Measuring S0 may include measuring the conductivity using the conductivity sensor 7. Next, measuring S0 includes pumping a sample of the low electrolyte solution into the conductivity sensor 7. For example, if the low electrolyte solution is a glucose solution, the method may include opening the three-way valve 10j downward toward the main line 20f, opening the dilute electrolyte container valve 10g, and using the dilute electrolyte pump 6 in the reverse direction to pump the glucose solution from the liquid container 34 to the conductivity sensor 7. Alternatively, the conductivity of the low electrolyte solution may be known, obtained, measured, or estimated. For example, if the low electrolyte solution is pure water, the conductivity is assumed to be zero. This conductivity can be used as a baseline for the conductivity of the solution produced from the second side 2b.

[0043] The method further includes passing S1 the electrolyte solution through the first side 2a. In other words, the method includes providing a flow of the electrolyte solution to the first side 2a. Thus, the electrolyte solution is passed through the inlet port E at a specific flow rate. in Inlet port E in from the outlet port E where the solution leaves the FO device 2 through the first side 2a for osmotic exchange through the FO membrane 2c. out The electrolyte solution may be, for example, a drain or a diluted electrolyte concentrate. If the electrolyte solution is a drain, the passage S1 is pumped from a drain container 35, a patient or other source fluidly connected to the inlet connector Pi, using a drain pump 3 and / or a drain pump 4, and opening and closing appropriate valves, and further from the inlet port E of the first side 2a. inThe flow path S1 includes pumping the effluent from the diluted electrolyte container 32 to the effluent container 35. If the electrolyte solution is a diluted electrolyte concentrate, the pumping includes pumping S1 a pre-prepared diluted electrolyte concentrate from the diluted electrolyte container 32 to the effluent container 35. The pumping is then performed using the effluent pump 3, opening valves 10p, 10d, and 10b, and closing valves 10c and 10a, to pump the diluted electrolyte concentrate through lines 20p, 20c, 20a, and 20b. The effluent container 35 is then empty, or if not, the effluent container 35 is then emptied for draining. The flow path S1 further includes pumping the diluted electrolyte concentrate or effluent from the effluent container 35 to the inlet port E of the first side 2a using the effluent pump 3 and / or the drain pump 4, opening valves 10b and 10d, and closing valves 10a, 10c, and 10p. in The passage S1 further includes feeding the electrolyte solution into the inlet port E of the first side 2a. in , passes through the first side 2a, and exits the outlet port E of the first side 2a. out to a drain (not shown) and opening valve 10e. The hydrostatic pressure on both sides 2a, 2b may be close to atmospheric pressure.

[0044] In some embodiments, the method includes passing the electrolyte solution through the first side 2a at a hydrostatic pressure S1 that is lower than the hydrostatic pressure at the second side 2b. This prevents solute migration from the first side 2a to the second side 2b, allowing for a more accurate assessment of the source of the integrity error. In other words, this embodiment includes configuring the hydrostatic pressure P1 at the first side 2a to be lower than the hydrostatic pressure P2 at the second side 2b. This configuration is implemented, for example, by measuring the hydrostatic pressure P1 at the first side 2a using a pressure sensor 8 and controlling the speed of the drain pump 4 based on the sensed pressure so that the hydrostatic pressure P1 is equal to the lower hydrostatic pressure. Outlet port L out The hydrostatic pressure at the second side 2b is typically constant because the first side 2a is open to atmospheric pressure via the diluted electrolyte container 32. Therefore, by varying the hydrostatic pressure P1 at the first side 2a, the transmembrane pressure (TMP) between the first side 2a and the second side 2b can be varied to a desired TMP.

[0045] The method further comprises passing S2 the low electrolyte solution to the second side 2b. The passing S2 of the low electrolyte solution is performed while passing S1 the electrolyte solution to the first side 2a. In other words, the method comprises providing a flow of the electrolyte solution to the second side 2b. Thus, the low electrolyte solution is provided to the inlet port Lin at a specific flow rate, and the low electrolyte solution is provided to the inlet port L in from the outlet port L through which the solution leaves the FO device 2 through the second side 2b for osmotic exchange through the FO membrane 2c. out The low electrolyte solution is, for example, a glucose solution or pure water. In the case of a glucose solution, passage S2 is performed by using the concentrate pump 5, opening valves 10j and 10h, and closing valves 10i, 10k, 10g, and 10f to allow the liquid to flow from the liquid container 34 to the inlet port L of the second side 2b. in For pure water, passage S2 involves pumping pure water from the pure water container 33 into the inlet port of the second side 2b using the concentrate pump 5 and optionally the dilute electrolyte pump 6, with valves 10k and 10h open and valves 10i, 10m, 10j (with line 20j closed), 10g, and 10f closed. The pure water is first pumped into the mixing unit 9 and then into the inlet port L. in The passage S2 further delivers the low electrolyte solution to the inlet port L of the second side 2b. in Then, it passes through the second side 2b and reaches the outlet port L of the second side 2b. out The low electrolyte solution is then pumped into the dilute electrolyte container 32, and the conductivity is sensed by the conductivity sensor 7. The first and second steps can be performed continuously and simultaneously during the test, so that the passes involve providing a continuous flow simultaneously on the first side 2a and the second side 2b. The passes S1 and S2 are performed to provide a specific flow rate of the electrolyte solution into the first side 2a, which, together with a specific flow rate of the low electrolyte solution on the second side 2b, results in a predetermined conductivity of the liquid produced from the second side 2b if the FO membrane is intact or has integrity.

[0046] Depending on the osmotic pressure difference between the electrolyte solution on the first side 2a and the low-electrolyte solution on the second side 2b, one solution is dehydrated and the other is diluted. The electrolyte solution typically has an osmotic pressure of approximately 8 bar (116 psig). If the low-electrolyte solution is a glucose solution containing a sufficient concentration of glucose, the osmotic pressure on the second side 2b will be higher than on the first side 2a. A glucose solution containing 6% glucose (the remaining 94% is typically pure water) will have an osmotic pressure of approximately 8 bar (116 psig). The glucose solution may therefore contain more than 6%, for example, at least 10%, at least 20%, or up to 50% glucose. Therefore, to have a sufficient concentration of glucose, the glucose solution may contain between 10% and 50% glucose. In the case of an intact FO membrane 2c, water then diffuses from the electrolyte solution on the first side 2a into the glucose solution on the second side 2b, thus diluting the glucose solution. Thus, in some embodiments, the method includes passing the low electrolyte solution through the second side 2b at a higher osmolality than the osmolality of the first side 2a, enabling diffusive water transport from the first side 2a to the second side 2b (S2). This mimics the actual operation of an FO water extraction session, where the patient's effluent or water is on the first side 2a and the dialysis concentrate is on the withdrawal side 2b. If the low electrolyte solution is pure water, the osmolality on the second side 2b will be lower than that on the first side 2a. The osmolality of pure water is typically zero or close to zero. In the case of an FO membrane 2c with integrity, water then diffuses from the pure water on the second side 2b into the electrolyte solution on the first side 2a, thus diluting the electrolyte solution. Thus, in some embodiments, the method includes passing the low electrolyte solution through the second side at a lower osmolality than the osmolality of the first side 2a (S2), enabling diffusive water transport from the second side 2b to the first side 2a. In the case of an integrity problem, such as a leak or anomalous diffusion, electrolytes are transported to the second side 2b, increasing the conductivity of the solution produced from the second side 2b. For example, in the case of a diffusion error in the FO membrane 2c, electrolytes can diffuse from the first side 2a to the second side 2b, increasing the conductivity of the solution at the second side 2b. In the case of a leak in the FO membrane 2c, electrolytes leak from the first side 2a to the second side 2b, increasing the conductivity of the solution at the second side 2b.The integrity of the FO membrane 2c is therefore assessed by measuring the conductivity of the low electrolyte solution discharged from the second side 2b. Accordingly, the method includes measuring S3 the conductivity of the solution produced from the second side 2b. Measuring S3 the conductivity may include monitoring the conductivity for a period of time until the conductivity stabilizes. Measuring S3 the conductivity is typically performed using a conductivity sensor 7. Accordingly, the method includes pumping the solution produced from the second side 2b through the conductivity sensor 7, measuring the conductivity, and further pumping the solution into the diluted electrolyte container 32.

[0047] The method further includes evaluating the integrity of the FO membrane 2c (S6) based on whether the measured conductivity satisfies one or more conductivity criteria, which may include or define the conductivity of a solution produced from the second side using an intact FO membrane with the same integrity and an equivalent electrolyte solution and an equivalent low-electrolyte solution. Thus, the method includes evaluating whether the FO membrane 2c has integrity based on the expected resulting conductivity of a solution produced from the second side 2a using the same equivalent liquid at the same operating point and with the same type of FO membrane with the same integrity. The conductivity criteria may include one or more threshold values ​​for the conductivity of the liquid produced from the second side 2b. The one or more threshold values ​​may be based on previous experiments using the same type of FO membrane with the same integrity and the same solution used, and the acceptable conductivity threshold values ​​are determined based on knowledge of the expected and acceptable electrolyte diffusion on the FO membrane 2c. Alternatively, or in combination, the one or more threshold values ​​may be based on the conductivity of the low-electrolyte solution. For example, the one or more threshold values ​​may define an acceptable change, e.g., an increase, from the conductivity of the low-electrolyte solution. If the change in conductivity is greater than a stored threshold change, the FO membrane can be determined to lack integrity. Thus, in some embodiments, the integrity assessment S6 includes determining that the FO membrane 2c lacks integrity if the measured conductivity exhibits a change in conductivity greater than a threshold value from the conductivity of the low-electrolyte solution. Thus, in such embodiments, the integrity assessment S6 can include calculating the change in conductivity from the conductivity of the low-electrolyte solution to the measured conductivity of the solution produced from the second side 2b and comparing the change in conductivity to a threshold value. The threshold value for the conductivity of the solution produced on the second side 2b can also be provided by a predefined table of conductivity values ​​stored in the memory of the controller 50 for a particular type and conductivity of the low-electrolyte solution.

[0048] The expected acceptable electrolyte diffusion can be expressed as a predetermined dilution ratio of the low electrolyte solution on the second side 2b. Thus, in some embodiments, the threshold value is based on the conductivity of the low electrolyte solution and a predetermined dilution ratio of the low electrolyte solution in the FO device 2. The dilution ratio depends on the solution used, the flow rate, and the properties of the FO membrane 2c. The dilution ratio can be defined as the volume / flow rate of the low electrolyte solution on the second side 2b compared to the volume / flow rate of the solution produced from the second side 2b. The dilution ratio can be estimated based on the current operating point of the FO device 2 (e.g., flow rates on sides 2a, 2b) and assumptions / knowledge about the composition of the electrolyte solution and the low electrolyte solution (e.g., their osmolality). The actual conductivity change, e.g., an increase or growth, can then be compared to this threshold value, and a conclusion can be made regarding the state of the electrolyte selectivity of the FO membrane 2c. The dilution ratio with glucose on the second side 2b is expected to be between 1:2 and 1:10, more precisely between 1:4 and 1:7, with the FO membrane 2c having integrity and one of the specific electrolyte solutions on the first side 2a. The dilution ratio with water on the second side 2b is expected to be between 1:0 and 1:1, more precisely between 1:0 and 1:0.5, with the FO membrane 2c having integrity and one of the specific electrolyte solutions on the first side 2a. The dilution of water occurs because water molecules diffuse from the pure water on the second side 2b to the first side 2a, thus concentrating the pure water or at least reducing the flow rate of the pure water.

[0049] Based on the above, a general lack of integrity of the FO membrane 2c can be determined. However, to understand the cause of the integrity error in more detail, the method can include establishing a hydrostatic pressure difference between the first side 2a and the second side 2b. This can determine whether the integrity error is due to a solute transport error and / or a diffusion error in the FO membrane 2c. Thus, if the passage S1 includes passing a low-electrolyte solution through the first side 2a at a hydrostatic pressure P1 lower than the hydrostatic pressure P2 at the second side 2b, the resulting lack of integrity of the FO membrane 2c indicates a solute diffusion error in the FO membrane 2c. Therefore, the lower hydrostatic pressure P1 at the first side 2a disables solute transport from the first side 2a to the second side 2b. A positive TMP difference (P2 minus P1) is then established from the second side 2b to the first side 2a. The TMP difference is at least 80 mmHg (1.5 psig), and in some embodiments, exceeds 200 or 300 mmHg (3.9 to 5.8 psig). The increase in conductivity of the solution produced on the second side 2b is the result of diffusive electrolyte transport from the first side 2a to the second side 2b. This eliminates one source of error that can lead to a loss of integrity, and therefore leakage. In the case of integrity, water is expected to diffuse from the second side 2b to the first side 2a or from the first side 2a to the second side 2b, depending on the difference in osmolarity. In the presence of a solute diffusion error, electrolytes diffuse from the first side 2a to the second side 2b, thereby increasing the conductivity of the solution produced on the second side 2b. This evaluation is sometimes referred to as a diffusion test.

[0050] However, integrity errors can also include solute transport errors, and thus leaks. To detect such errors, the method includes (i) passing an electrolyte solution through the first side 2a at a hydrostatic pressure lower than that of the second side 2b (S1), measuring the conductivity of the resulting solution from the second side 2b (S3), and then (ii) passing the electrolyte solution through the first side 2a at a hydrostatic pressure higher than that of the second side 2b (S4). A low electrolyte flow is provided as previously described in step S3 and exists on the second side 2b. Thus, the method includes configuring the hydrostatic pressure P1 of the first side 2a to be higher than that of the second side 2b. This configuration is implemented, for example, by measuring the hydrostatic pressure P1 of the first side 2a using a pressure sensor 8 and controlling the speed of the drain pump 4 based on the sensed pressure so that the hydrostatic pressure P1 is equal to the desired higher hydrostatic pressure. For example, the configuration may include slowing down the speed of the drain pump 4 so that P1 is higher than P2 (P1>P2). As will be explained, the outlet port L outBecause the first side 2a is open to atmospheric pressure via the diluted electrolyte container 32, the hydrostatic pressure P2 at the second side 2b is typically constant. Therefore, by varying the hydrostatic pressure P1 at the first side 2a, the transmembrane pressure (TMP) between the first side 2a and the second side 2b can be varied to the desired TMP. Step S4 of the method may therefore include changing the pressure compared to step S1 of the method so that the TMP gradient is reversed. Therefore, the method includes measuring the conductivity of the solution produced from the second side 2b (S5). Measuring the conductivity (S5) may include monitoring the conductivity for a period of time until the conductivity stabilizes. Therefore, the conductivity is measured again while passing a liquid having a different hydrostatic pressure difference than during the previous conductivity measurement in step S3. If a leak is present, electrolyte solution can flow through the leak from the first side 2a to the second side 2b. Therefore, if a leak exists, solute transport from the first side 2a to the second side 2b is possible because the hydrostatic pressure is lower on the second side 2b than on the first side 2a. In the event of a leak, the electrolyte solution flowing from the first side 2a to the second side 2b increases the conductivity of the solution produced on the second side 2b compared to the conductivity previously measured in step S3. Thus, the change in conductivity will be larger. Thus, the method may include determining the change in conductivity based on the conductivity measurement in step S3, determining the change in conductivity based on the change in conductivity in step S5, and comparing the changes, and if the change in conductivity based on the conductivity in step S5 is larger than that determined based on the conductivity in step S3, the leak is determined to be the result of convective electrolyte transport from the first side 2a to the second side 2b. In other words, in some embodiments, the method includes determining S6 that the lack of integrity of the FO membrane 2c is due to leakage (solute migration) in the FO membrane 2c when the measured conductivity exhibits a larger conductivity change than the conductivity change detected at the higher hydrostatic pressure on the second side 2b, the conductivity change being determined from the same criteria.The direction of solute transfer (leakage) flow tested here is from the first side 2a to the second side 2b, which is the most critical from a risk perspective due to the risk of contamination of the effluent components on the second side 2b, through which the dialysis concentrate / dialysate should flow. This type of evaluation is sometimes called a solute transfer test.

[0051] The results may be communicated to the user via a user interface of the control device 10 (not shown, in communication with the control unit 50) and / or an alarm may be activated if an integrity error is detected. The user can then take appropriate action in the event of an integrity error, such as replacing the FO device.

[0052] Tests were conducted to evaluate how the conductivity of the low-electrolyte solution changes with the addition of electrolyte solution. A low-electrolyte solution was prepared by mixing 100 ml of glucose concentrate with 500 ml of purified water, representing the expected dilution of the glucose concentrate used in this method. An electrolyte solution was prepared by mixing 10 ml of buffer concentrate with 150 ml of ELIX® water (Merck), representing a typical dilution of the electrolyte concentrate used in this method. The electrolyte solution was added to the low-electrolyte solution in incremental portions and mixed. The conductivity of the mixture was measured to determine the relationship between the percentage of electrolyte solution added and the volume and conductivity of the low-electrolyte solution. The results are shown in Figure 4, where one axis represents the conductivity of the mixture in mS / cm and the other axis represents the percentage of electrolyte solution (volume fraction of contaminant) in the total mixture. The baseline conductivity of 0.06 mS / cm is due to the conductivity of the low-electrolyte solution without the addition of electrolyte solution. This conductivity is due to the low-electrolyte content of hydrochloric acid. As can be seen, a clear increase in conductivity was observed with the added percentage / volume of electrolyte solution.

[0053] The method was also tested using an intact FO membrane (intact membrane) and then using the same membrane with a single broken fiber (membrane with a single break).TM The test was performed on a Hollow Fiber Forward Osmosis 2 (HFFO2) manufactured by the company HFFO2. The test results are shown in Table 1.

[0054] [Table 1]

[0055] The low electrolyte solution was a glucose solution with 50% glucose concentrate and 50% water. The electrolyte solution was a buffer solution containing electrolyte concentrate diluted 1:19 with water. The transmembrane pressure (TMP) was measured as P2 minus P1. The same FO membrane was used throughout the tests.

[0056] The first two tests in Table 1 were performed with an intact FO membrane. The conductivity of the solution produced from the second side 2b was elevated compared to the conductivity of the original glucose solution (0.06 mS / cm), suggesting that electrolytes were transported from the first side 2a to the second side 2b. The fact that the increase in conductivity was largely unaffected by TMP indicates that the increase in conductivity was the result of diffusive transport of electrolytes across the membrane rather than solute transport.

[0057] The last two tests in Table 1 were performed using the same FO membrane used during the first test, but with one broken fiber. When the TMP had a positive sign (thus disabling solute transport from the first side 2a to the second side 2b), the conductivity of the solution produced on the second side 2b was similar (although actually somewhat lower) to that observed with an intact membrane. When the TMP changed to a negative sign (thus enabling solute transport from the first side 2a to the second side 2b), the conductivity of the solution produced on the second side 2b was significantly higher than in all other tests, indicating that solute transport was occurring. Therefore, a broken fiber could be detected.

[0058] Varying the TMP from 82 mmHg to -180 mmHg during tests 1 and 2 (intact FO membrane) increased the driving force for diffusive water transport across the membrane, resulting in an increase in Lout The flow rate from the membrane increased by 4.2 ml / min. Since almost the same TMP change was introduced between Tests 3 and 4 (FO membrane with fiber breaks), the flow rate from the membrane increased by 4.2 ml / min. out The flow rate from the second side 2b increased by 11.6 ml / min. Assuming that the increment in the rate of TMP-driven diffusive water transport is identical between the intact and ruptured membranes, the difference in increments (11.6 - 4.4 = 7.2 ml / min) is the solute transport of the electrolyte solution to the second side 2b. This means that the liquid produced from the second side 2b contained 8.3% of the feed solution. The sensitivity of the method can be increased by using a TMP much lower than -180 mmHg during the solute transport test.

[0059] The present disclosure also includes a controller 10 for evaluating the integrity of a forward osmosis (FO) membrane 2c of an FO device 2 in a dialysate generating apparatus 1. The FO device 2 is configured to be used in an FO session to dilute a dialysis concentrate in a process of generating dialysate. An FO session thus refers to diluting a dialysis concentrate. The FO membrane 2c separates a first side 2a of the FO device 2 from a second side 2b. The controller 10 includes an effluent pump 3 configured to provide a flow of an electrolyte solution. The controller 10 further includes a concentrate pump 5 configured to provide a flow of a low-electrolyte solution. The controller 10 also includes a conductivity sensor 7 configured to sense the conductivity of the solution generated from the second side 2b. The controller 10 is configured to pass the electrolyte solution through the first side 2a using the effluent pump 3. The controller 10 is also configured to pass the low-electrolyte solution through the second side 2b using the concentrate pump 5. The controller 10 is further configured to measure the conductivity of the solution generated from the second side 2b using the conductivity sensor 7. The control device 10 is also further configured to evaluate the integrity of the FO membrane based on whether the measured conductivity meets a conductivity criterion, the conductivity criterion including or defining the conductivity of a solution produced from the second side using an intact or intact FO membrane with an equivalent electrolyte solution and an equivalent low electrolyte solution.

[0060] The control device 10 is configured to determine a lack of integrity of the FO membrane 2c when it determines that the measured conductivity exhibits a conductivity change from the conductivity of the low electrolyte solution that is greater than a threshold conductivity change.

[0061] In some embodiments, the control device 10 is configured to pass the low-electrolyte solution through the second side 2b at a hydrostatic pressure lower than the hydrostatic pressure at the first side 2a, thereby disabling solute transfer from the first side 2a to the second side 2b. The determined lack of integrity of the FO membrane 2c indicates a diffusion error of the solute through the FO membrane 2c.

[0062] In some embodiments, the controller 10 is configured to (i) pass a low-electrolyte solution at the second side 2b at a hydrostatic pressure higher than the hydrostatic pressure at the first side 2a, (ii) measure the conductivity of the solution produced from the second side using the conductivity sensor 7, and (iii) determine that the lack of integrity of the FO membrane 2c is due to a leak in the FO membrane 2c when it determines that the measured conductivity exhibits a conductivity change that is greater than the conductivity change produced at the higher hydrostatic pressure at the second side.

[0063] In some embodiments, the control device 10 is configured to pass the low electrolyte solution through the second side 2b at an osmotic pressure higher than the osmotic pressure on the first side 2a, thereby enabling diffusive water transport from the first side 2a to the second side 2b, or to pass the low electrolyte solution through the second side at an osmotic pressure lower than the osmotic pressure on the first side 2a, thereby enabling diffusive water transport from the second side 2b to the first side 2a.

[0064] In some embodiments, the controller 10 is configured to control the hydrostatic pressure using the drain pump 4. The controller 10 may be configured to perform any one of the aspects, embodiments or examples described herein.

[0065] 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 embodiments, but on the contrary, is intended to cover various modifications and equivalent arrangements included within the scope of the appended claims.

Claims

1. 1. A method of operating a dialysate generator (1) for assessing the integrity of a forward osmosis (FO) membrane (2c) of a FO device (2) in the dialysate generator (1), the FO device (2) being configured for use in an FO session for diluting a dialysis concentrate in a process for producing dialysate, the FO membrane (2c) separating a first side (2a) and a second side (2b) of the FO device (2), the method comprising: Passing an electrolyte solution through the first side (2a) (S1); Passing a low electrolyte solution through the second side (2b) (S2); Measuring the conductivity of the solution produced from the second side (2b) (S3); and evaluating (S6) the integrity of the FO membrane (2c) based on whether the measured conductivity satisfies a conductivity standard, the conductivity standard including the conductivity of a solution produced from the second side (2b) using an FO membrane having integrity and using an equivalent electrolyte solution and an equivalent low electrolyte solution.

2. 2. The method of claim 1, wherein the evaluating the integrity (S6) includes determining a lack of integrity of the FO membrane when the measured conductivity exhibits a change in conductivity from the conductivity of the low electrolyte solution that is greater than a threshold value.

3. 3. The method of claim 2, wherein the threshold value is based on the conductivity of the low electrolyte solution and a predetermined dilution ratio of the low electrolyte solution in the FO device.

4. 3. The method of claim 2, comprising passing (S1) the electrolyte solution through the first side (2a) at a hydrostatic pressure lower than the hydrostatic pressure at the second side (2b), thereby disabling solute transfer from the first side (2a) to the second side (2b), whereby a determined lack of integrity of the FO membrane indicates a solute diffusion error in the FO membrane.

5. 5. The method of claim 4, comprising: passing the electrolyte solution through the first side (2a) at a hydrostatic pressure higher than the hydrostatic pressure on the second side (2b) (S4); measuring the conductivity of the solution produced from the second side (2b) (S5); and determining that the lack of integrity of the FO membrane is due to a leak in the FO membrane when the measured conductivity exhibits a conductivity change greater than the conductivity change detected at the first side (2a) at the lower hydrostatic pressure (S6).

6. 2. The method of claim 1, comprising: (i) passing a low electrolyte solution through the second side (2b) at an osmotic pressure higher than that of the first side (2a), thereby enabling diffusive water transport from the first side (2a) to the second side (2b) (S2); or (ii) passing a low electrolyte solution through the second side (2b) at an osmotic pressure lower than that of the first side (2a), thereby enabling diffusive water transport from the second side (2b) to the first side (2a) (S2).

7. 2. The method of claim 1, wherein the low electrolyte solution is a glucose solution.

8. 2. The method of claim 1, wherein the low electrolyte solution is water.

9. 10. The method of claim 1, wherein the electrolyte solution is effluent from a dialysis treatment.

10. 10. The method of claim 1, wherein the electrolyte solution is a diluted electrolyte concentrate.

11. 10. The method of claim 1, wherein the low electrolyte solution has a conductivity in the range of 0 to 0.5 mS / cm.

12. The method of claim 11, wherein the low electrolyte solution has a conductivity of less than 0.1 mS / cm.

13. 1. A control device (10) for assessing the integrity of a forward osmosis (FO) membrane (2c) of a forward osmosis (FO) device (2) in a dialysate generating apparatus (1), the FO device (2) being configured for use in an FO session for diluting a dialysis concentrate in a process for generating dialysate, the FO membrane (2c) separating a first side (2a) and a second side (2b) of the FO device (2), the control device (10) comprising: a discharge pump (3) configured to provide a flow of electrolyte solution; a concentrate pump (5) configured to provide a flow of low electrolyte solution; a conductivity sensor (7) configured to sense the conductivity of the solution produced from the second side (2b); The control device (10) Using the effluent pump (3), an electrolyte solution is passed through the first side (2a); using the concentrate pump (5) to pass a low electrolyte solution through the second side (2b); using said conductivity sensor (7) to measure the conductivity of the solution produced from said second side (2b); The control device is configured to evaluate the integrity of the FO membrane (2c) based on whether the measured conductivity satisfies a conductivity standard, the conductivity standard including the conductivity of a solution produced from the second side (2b) using an FO membrane having integrity and an equivalent electrolyte solution.

14. 14. A solution generator (1) for producing a dialysis solution, the solution generator comprising a forward osmosis (FO) device (2) including an FO membrane (2c) separating a first side (2a) and a second side (2b) of the FO device (2), the solution generator further comprising a control device (10) according to claim 13.

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