Evaluation of the integrity of a forward osmosis membrane using the intermembrane pressure difference.
The method evaluates FO membrane integrity by monitoring TMP during and after flow cessation, addressing undetected integrity issues in FO membranes to ensure dialysate quality.
Patent Information
- Authority / Receiving Office
- JP · JP
- Patent Type
- Patents
- Current Assignee / Owner
- GAMBRO LUNDIA AB
- Filing Date
- 2022-04-05
- Publication Date
- 2026-05-25
AI Technical Summary
Existing forward osmosis (FO) membranes used in dialysate generation are prone to undetected integrity issues, allowing the transport of components other than water, which compromises the quality of the generated dialysate.
A method and control device are employed to evaluate the integrity of FO membranes by monitoring transmembrane pressure difference (TMP) during and after flow cessation, utilizing existing components in the dialysis system to assess integrity based on pressure parameters such as magnitude, time to reach maximum TMP, and relaxation rate.
This approach provides a simple and reliable means to detect and assess the severity of integrity errors in FO membranes, ensuring the quality of dialysate production by preventing the transport of non-water components across the membrane.
Smart Images
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Abstract
Description
Technical Field
[0001] The present disclosure relates to the field of dialysis and the integrity testing of forward osmosis membranes, and more particularly to evaluating the integrity of a forward osmosis membrane disposed in a dialysate generation device.
Background Art
[0002] Dialysis is commonly used to treat patients suffering from kidney failure. There are multiple types of dialysis treatments such as hemodialysis (HD), peritoneal dialysis (PD), and continuous renal replacement therapy (CRRT). Typically, dialysate is used in the treatment, and the dialysate is delivered as pre-made in a bag or generated at the time of use by mixing a concentrate and water.
[0003] Forward osmosis (FO) has emerged as an option for generating dialysate because of its potential to reduce water consumption. FO membranes are typically designed to be more or less selective for water molecules, thereby enabling the FO membrane 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, it is necessary to detect such integrity problems so that the generated dialysate is not compromised.
Summary of the Invention
[0005] The FO membranes of the present disclosure are used to prepare dialysate. The FO membranes are, in one embodiment, more or less selective with respect to water molecules, whereby the FO membranes enable separation of water from all other contaminants. The osmotic pressure difference between the feed solution (e.g., water or effluent from 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, whereby the dialysis concentrate is diluted. The diluted dialysis concentrate is then used to generate dialysate. The systems and methods of the present disclosure enable detection of integrity issues with the FO membranes and suppression of changes in the composition of the dialysate produced by transport of components other than water across the FO membranes.
[0006] Therefore, an object of the present disclosure is to provide a simple and reliable method for evaluating the integrity of a forward osmosis membrane. A further object is to provide a method for evaluating the integrity of a forward osmosis membrane during online or dialysate preparation.
[0007] These and other objects are at least partially achieved by the method, control device, and dialysate generation device according to the independent claims, and by the embodiments according to the dependent claims.
[0008] In one embodiment which can be combined with any other aspect and its embodiments, the present disclosure relates to a method for evaluating the integrity of a forward osmosis (FO) membrane in a dialysate generator. The FO membrane separates the feed side of the FO device from the draw side. The FO device comprises a feed inlet port and a feed outlet port which are in fluid communication with the feed side, and a draw inlet port and a draw outlet port which are in fluid communication with the draw side. The method includes providing a flow of feed solution to the feed side through the feed inlet port, and providing a flow of draw solution to the draw side through the draw inlet port at an osmotic pressure on the draw side that is higher than the osmotic pressure on the feed side, thereby extracting water from the feed side to the draw side and diluting the draw solution. The method further includes stopping the flow through the draw inlet port, the feed inlet port, and the feed outlet port, thereby allowing water to continue to be extracted from the feed side to the draw side until the 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 indicating TMP, and evaluating the integrity of the FO film based on one or more monitored parameters, including one or more pressures indicating TMP.
[0009] The method provides a simple and reliable way to assess the integrity of a FO membrane. Integrity errors can be detected based on one or more pressures indicating a maximum TMP. For an intact FO membrane, the maximum TMP is expected to remain more or less constant and decrease very slowly. For an intact FO membrane, 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 (accompanied by diffusive water transport from the draw side to the feed side) may occur. In either case, the hydrostatic pressure on the feed side increases, leading to a decrease in the maximum TMP and / or a relatively rapid decrease in TMP after reaching the maximum TMP. This behavior is used to assess the integrity of the FO membrane. The method is easy to implement because it uses features already present in the dialysis solution generator and can be performed automatically without human intervention.
[0010] According to some embodiments, the integrity assessment includes evaluating the properties of one or more pressures indicating a TMP or TMP, including one or more of the following: magnitude, time to reach maximum value, and / or relaxation. This can provide information regarding the integrity of the FO film.
[0011] According to some embodiments, integrity assessment includes evaluating the relaxation of TMP based on one or more monitored pressures indicating TMP. The relaxation assessment allows for the detection of small integrity errors.
[0012] According to some embodiments, the method includes evaluating the integrity of a FO film based on the magnitude of the relaxation rate of a TMP, which is determined based on one or more monitored pressures exhibiting a TMP. The magnitude evaluation also allows for the detection of small integrity errors.
[0013] According to some embodiments, the method includes assessing integrity based on the achievement of one or more integrity criteria for the magnitude of the relaxation rate of the TMP. The assessment of the integrity criteria allows for the determination of the severity of the integrity error.
[0014] According to some embodiments, the assessment of the integrity of the FO film includes evaluating its integrity based on one or more monitored parameters, including one or more pressures that indicate a TMP during the period after the shutdown has occurred, where one or more pressures should reflect any integrity errors during such a period.
[0015] According to some embodiments, the maximum value of TMP is characterized by the relaxation rate of TMP at zero magnitude. Here, the maximum value of TMP may be defined as the TMP at the point of maximum after the flow has stopped.
[0016] According to some embodiments, the method includes determining a maximum value of TMP based on one or more monitored pressures indicating TMP, controlling the flow of a solution through a feed inlet port or a feed outlet port so that TMP corresponds to the determined maximum value of TMP based on one or more monitored pressures indicating TMP and the determined maximum value of TMP, and monitoring one or more parameters indicating the flow rate of the resulting flow of the solution. Herein, an alternative method for evaluating integrity is achieved.
[0017] According to some embodiments, control includes controlling the speed of the feed pump, monitoring includes monitoring the speed of the feed pump, and integrity evaluation includes evaluating the integrity of the FO film based on the monitored speed of the feed pump. Thus, since the speed of the feed pump is readily available in the control device, a method that is easily achieved is provided.
[0018] According to some embodiments, the method includes assessing integrity based on the achievement of one or more integrity criteria of one or more parameters indicating the flow rate of the resulting flow from the feed solution. The integrity criteria allow for determining the severity of an integrity error.
[0019] According to some embodiments, the draw outlet port is connected to a dilution / concentrate container. Thus, the draw side is connected to atmospheric pressure or near-atmospheric pressure, which is typically kept constant during the implementation of the method.
[0020] According to some embodiments, the monitor includes monitoring one or more pressures, including a pressure indicating the feed-side pressure, and / or monitoring one or more pressures, including a pressure indicating the draw-side pressure. Thus, the TMP can be derived in multiple ways.
[0021] According to some embodiments, the method includes increasing the hydrostatic pressure on the feed side to be greater than the hydrostatic pressure on the draw side. The method then includes monitoring one or more pressures indicating a TMP and evaluating the integrity of the FO membrane based on one or more monitored parameters, including one or more pressures indicating a TMP. Thus, by establishing a bulk pressure on the feed side, leaks present only on the draw side from the feed side can be distinguished.
[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 in a dialysate generator. The FO membrane separates the feed side from the draw side of the FO device. The FO device comprises a feed inlet port and a feed outlet port which are in fluid communication with the feed side, and a draw inlet port and a draw outlet port which are in fluid communication with the draw side. The control device comprises a feed pump configured to provide a flow of feed solution to the feed side via the feed inlet port, and a draw pump configured to provide a flow of draw solution to the draw side via the draw inlet port at an osmotic pressure on the draw side that is higher than the osmotic pressure on the feed side, thereby enabling the 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 indicating 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 control unit is further configured to use a feed pump, a draw pump, and a valve device to stop the flow through the draw inlet port, the feed inlet port, and the feed outlet port, thereby allowing water to continue to be drawn from the feed side to the draw side until the transmembrane pressure difference (TMP) between the draw side and the feed side reaches its maximum value. The control unit is further configured to monitor one or more pressures indicating the TMP using one or more pressure sensors and to evaluate the integrity of the FO membrane based on one or more monitored parameters, including one or more pressures indicating the TMP.
[0023] According to some embodiments, the control device according to the second embodiment is configured to perform any one of the embodiments according to the first embodiment.
[0024] According to a third aspect which can be combined with any other aspect and its embodiments, the present disclosure relates to a solution generating apparatus for generating dialysate. The apparatus comprises a forward osmosis device having an FO membrane separating the feed side and the draw side of the FO device. The apparatus further comprises a control device according to the second aspect.
[0025] According to the fourth aspect, the disclosure relates to a computer program that includes instructions causing a control device according to the second aspect to perform the method according to the first aspect.
[0026] According to the fifth aspect, the disclosure relates to a computer-readable medium storing a computer program of the fourth aspect. [Brief explanation of the drawing]
[0027] [Figure 1] Figure 1 is a schematic diagram of an FO device according to some embodiments of the present disclosure. [Figure 2] Figure 2 shows examples of dialysate generating devices according to several embodiments of the present disclosure. [Figure 3] Figure 3 shows a method for evaluating the integrity of the FO film in an FO device according to several embodiments of the present disclosure. [Figure 4] Figure 4 shows the test results obtained from implementing the method shown in Figure 3. [Modes for carrying out the invention]
[0028] The following description outlines methods for evaluating the integrity of forward osmosis (FO) membranes. FO membranes are used in FO devices of dialysis generators to produce dialysate, and are subsequently used to produce dialysate. Dialysis can be used in PD, HD, CRRT, or any other dialysis treatment that uses dialysate as a therapeutic or replacement fluid (e.g., to dilute filtered blood).
[0029] In detail, FO membranes are used to extract water into the dialysate from patient drainage fluid, tap water, or other water sources to produce dialysate. Membrane integrity can be defined as the quality or state of a complete membrane under perfect conditions. Thus, an FO membrane with integrity is intact and free from any damage or malfunction. FO membranes can experience compromised integrity due to, for example, manufacturing errors or wear. Compromised integrity can lead to integrity problems such as leaks (solute transport) or decreased selectivity, which can result in an increased rate of diffusive solute transport (solute flux) through the FO membrane. Undetected integrity problems can alter the composition of the dialysate produced by allowing the transport of non-water components across the FO membrane. For example, leaks can allow the transport of microorganisms from the feed side (drainage fluid or tap water) to the draw side (mixing side), potentially increasing the risk of peritonitis, for example, in the case of PD. Furthermore, leaks can allow the transport of solutes (electrolytes, glucose, urea, etc.) from the feed side (fluid or tap water) to the draw side (mixing side), thereby altering the composition of the resulting dialysate. Increased rates of diffusive electrolyte transport also pose a risk of solutes (electrolytes, glucose, urea, etc.) diffusing across the FO membrane in one or both directions at a rate that significantly alters the composition of the resulting dialysate. The drainage fluid may include patient drainage during PD and / or used dialysate during HD or CRRT.
[0030] As described in this disclosure, it has been found that after the FO membrane is installed in the dialysis fluid generator, it is possible to detect such integrity problems by stopping the flow to and from the FO device and monitoring the resulting TMP or one or more pressures indicating the resulting TMP. For example, properties such as magnitude, time to reach 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 the flow is stopped, thereby the assessment of integrity may be made based on the flow rate, pump speed, or power to the pump obtained from a pump controlled to maintain the TMP at the maximum TMP.
[0031] Generally, the diffusion transport of water and solute is driven by a concentration difference of the solute, for example, the concentration difference between the feed side and the draw side. Solute movement (caused by leaks) is driven by a transmembrane pressure difference (TMP), for example, the pressure difference between the feed side and the draw side.
[0032] In some embodiments, the evaluation relies on existing technologies and concentrates used to produce dialysate. For example, a pressure sensor for sensing the pressure on the feed side already exists. The solution used is one already used to produce dialysate, such as tap water, wastewater from dialysis treatment, or dialysate concentrate.
[0033] Embodiments of the present disclosure will be described below with reference to Figures 1 to 4. Figure 1 is a schematic diagram of a single FO device 2 according to several embodiments. The FO device 2 comprises a first side 2a and a second side 2b separated by an FO membrane 2c. For ease of illustration and explanation, the left first side 2a will be called the feed side and the right second side 2b will be called the draw side. However, depending on the direction of the osmotic pressure difference of the liquids flowing on both sides 2a and 2b, the first side 2a may also be called the draw side and the second side 2b the feed side. The side may also be called a compartment or chamber in this specification. During use, the FO membrane 2c separates the solution on the feed side (called the feed solution) and the solution on the draw side (called 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 treatment, 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 permeable water molecules, thereby allowing the FO membrane 2c to separate water from all other contaminants. Thus, the FO membrane 2c is a permeable membrane. The FO membrane 2c typically has pore sizes in the nanometer (nm) range, e.g., 0.5 to 5 nm or less, depending on the solute intended to be blocked. The FO device 2 typically includes a feed side 2a, a draw side 2b, and a cartridge surrounding the FO membrane 2c. The shape of the FO membrane 2c can be a flat sheet, tubular, or hollow fiber. The feed side 2a has an inlet port E through which the feed solution enters the feed side 2a. in Then, the feed solution exits from the feed side 2a to the outlet port E. out It has the following: The draw side 2b has an inlet port L into which the draw solution enters the draw side 2b. in Then, the draw solution exits from the draw side 2b through the outlet port L. out It has and. Therefore, the liquids on both sides typically flow countercurrently, but may instead flow parallel. The flow is continuous. A suitable FO device for FO device 2 is, for example, AquaporinTM 、Asahi KASEI TM 、Berghof TM 、CSM TM 、FTSH2O TM 、Koch Membrane Systems TM 、Porifera TM 、Toyobo TM and Toray TM may be provided by.
[0034] The feed solution is, for example, a current or previous dialysis treatment or effluent from water. In some embodiments, the effluent has an osmotic pressure of about 8 bar (116 psig). Water typically has an osmotic pressure far below 1 bar (14.5 psig). The draw solution is, for example, a dialysis concentrate, and the extracted water dilutes the dialysis concentrate into a dialysis solution that may also be referred to as a "diluted dialysis concentrate", "intermediate dialysis solution" or simply "dialysis solution". The dialysis concentrate is, for example, a concentrate containing at least one of a plurality of NaCl, KCl, CaCl2, MgCl2, HAc, glucose, lactate and bicarbonate. For example, the dialysis concentrate may contain NaCl, CaCl2, MgCl2 and Na-lactate. Such a dialysis concentrate may have an osmotic pressure 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 osmotic pressure of up to 260 bar (3770 psig). Thus, the osmotic pressure of the dialysis solution concentrate is typically higher 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] Figure 2 shows a dialysate generating apparatus 1 (hereinafter, "apparatus 1") according to several embodiments of the present disclosure. Apparatus 1 comprises an FO device 2 described with reference to Figure 1. Apparatus 1 also comprises a flow path 20 comprising a plurality of liquid lines 20a to 20n, hereinafter referred to as "lines". Apparatus 1 further comprises a control device 30. The control device 30 comprises a feed pump 3, a draw pump 5, and a dilution dialysate concentrate pump 6. Any of the pumps herein may be a positive displacement pump (such as a piston pump) or a non-positive displacement pump (e.g., a gear pump) having flow rate feedback from, for example, a flow sensor (not shown). The feed pump 3 is connected to an inlet connector P i The feed pump 3 is configured to send the drainage fluid from the connected patient to the drainage fluid container 35, depending on the valve status. iThe apparatus 1 is configured to provide a flow of discharge fluid from the first side 2a to the first side 2a and from the first side 2a to a drain (not shown). Depending on the state of the valve, the draw pump 5 is configured to provide a flow of dialysate concentrate from the dialysate concentrate container 31 to the second side 2b, and further to deliver the solution produced in the second side 2b to the dilution concentrate container 32. The pure water container 33 contains pure water. The liquid container 34 contains an osmotic agent or buffer solution, such as glucose or bicarbonate. The apparatus 1 also includes 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 conductivity in the range of 0.1 to 40 mS / cm. The conductivity sensor may also include a temperature sensor (not shown) to compensate for the sensed conductivity value. The apparatus 1 further includes one or more pressure sensors configured to sense pressure indicating the transmembrane pressure difference (TMP) of the FO device 2. For example, the apparatus 1 includes a pressure sensor 8 positioned to sense the pressure on the feed side 2a. The apparatus 1 may also include an additional pressure sensor, for example, a pressure sensor positioned to sense the pressure on the draw side 2b. The dilution dialysis concentrate pump 6 is configured to provide a flow of liquid to the main line 20f. The control device 30 also includes a valve device 10 comprising a plurality of valves 10a to 10m. Generally, valves connected to a line can be configured to be open, allowing the flow of liquid in the line, and closed, stopping the flow of liquid in the line. The valves may be, for example, on / off valves, where the on state is when the flow of liquid in the line is allowed, and the off state is when the flow of liquid in the line is stopped. The control device 30 further includes a control unit 50 comprising at least one memory and at least one processor. The control device 30 is configured to control the valves of the pump and valve device 10 and the functions of the mixing unit 9 in order to perform several different processes, such as diluting the dialysis concentrate into the dialysis solution, supplying the dialysis solution, and performing a washing or priming process, as controlled by the control unit 50. The control device 30 is also configured to receive conductivity measurements from the conductivity sensor 7.The control device 30 is further configured to receive pressure measurements from one or more pressure sensors, including pressure sensor 8. Specifically, the control device 30 is configured to evaluate the integrity of the FO film 2c in the device 1, as defined by the method shown in Figure 3. For this purpose, at least one memory contains instructions for evaluating the integrity of the FO film 2c. When the instructions are executed by at least one processor, the control device 30 performs the method for evaluating the integrity of the FO film 2c, which is described below. The method may be performed by the control device 30 and stored as a computer program containing computer instructions in at least one memory.
[0036] However, first, the device 1 in Figure 2 will be described in more detail. In Figure 2, the inlet connector P i and feed inlet port E in To connect the first discharge liquid inlet line 20a to the inlet connector P i and the feed inlet port E on the first side 2a in It is placed between the following. Inlet connector P iIt can be connected, for example, to the drainage line or catheter of a PD patient, or to the used dialysate line of an HD device or CRRT device. A first drainage inlet valve 10a is connected to the first drainage inlet line 20a. A second drainage inlet line 20b is positioned between the first drainage inlet line 20a and the drainage container 35 to connect the first drainage inlet line 20a to the drainage container 35. A feed pump 3 is positioned to provide drainage flow in the second drainage inlet line 20b. A second drainage inlet valve 10b is connected to the second drainage inlet line 20b. A third drainage inlet line 20c is positioned between the first drainage inlet line 20a and the second drainage inlet line 20b to connect the first drainage inlet line 20a and the second drainage inlet line 20b. A third drainage inlet valve 10c is connected to the third drainage inlet line 20c. The fourth discharge inlet valve 10d is connected to the first discharge inlet line 20a, which is located between the connection point between the second discharge inlet line 20b and the third discharge inlet line 20c and the first discharge inlet line 20a. The discharge liquid can be collected in the discharge liquid container 35 by opening the first discharge inlet valve 10a and the second discharge inlet valve 10b, closing the third discharge inlet valve 10c and the fourth discharge inlet valve 10d, and using the feed pump 3 to send the discharge liquid into the container 35. Subsequently, the discharge liquid can be sent from the discharge liquid container 35 to the feed side 2a by the feed pump 3 by opening the second discharge inlet valve 10b and the fourth discharge inlet valve 10d and closing the first discharge inlet valve 10a and the third discharge inlet valve 10c. Instead, the discharge fluid opens the first discharge fluid inlet valve 10a and the third discharge fluid inlet valve 10c, closes the second discharge fluid inlet valve 10b and the fourth discharge fluid inlet valve 10d, and flows through the first discharge fluid inlet line 20a, the second discharge fluid inlet line 20b and the third discharge fluid inlet line 20c, and into the inlet connector P i The discharged liquid may be sent directly to the first side 2a by the feed pump 3.
[0037] The discharge liquid outlet line 20d is connected to the feed outlet port E on the first side 2a. outIt is positioned between the drain (not shown) and the feed outlet port E on the first side 2a. out The drain is connected to the drain outlet valve 10e, which is connected to the drain outlet line 20d. Thus, the FO device 2 has fluid communication with the feed side 2a and the feed inlet port E. in and feed exit port E out It is equipped with.
[0038] Furthermore, the dialysis concentrate container 31 and the draw inlet port L of the draw side 2b in To connect the two, the dialysis concentrate line 20e connects the dialysis concentrate container 31 to the draw inlet port L of the draw side 2b. in A draw pump 5 is positioned between the two lines to provide flow to the dialysis concentrate line 20e. The main line 20f is positioned between the dialysis concentrate line 20e and the mixing unit 9, connecting the dialysis concentrate line 20e and the mixing unit 9. The mixing unit 9 includes liquid mixing functions such as a main pump to control the flow rate obtained in line 20m downstream of the mixing unit 9, a liquid pump to provide flow of, for example, a 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. To connect the dilution concentrate container 32 and the main line 20f, a dilution concentrate container line 20g is positioned between the dilution concentrate container 32 and the main line 20f. A conductivity sensor 7 is connected to the dilution concentrate container line 20g to sense the conductivity of the diluted dialysis concentrate in the dilution concentrate container line 20g. The 10g diluted concentrate container valve is connected to the 20g diluted concentrate container line. The draw outlet port L is on the draw side 2b. out To connect the 20g dilution / concentrate container line, the first connection line 20h connects to the draw outlet port L of the draw side 2b. out It is positioned between the and the dilution / concentration solution container line 20g. Therefore, the FO device 2 has a draw inlet port L that is in fluid communication with the draw side 2b. in and draw exit port L outThe device is equipped with the following: A first main valve 10h is connected to the main line 20f between the connection point of the main line 20f and the dialysate concentrate line 20e, and the connection point of the dilution concentrate container line 20g and the main line 20f. The dialysate concentrate can be fed from the dialysate concentrate container 31 to the dilution concentrate container 32 via the draw side 2b by using the draw pump 5 and closing the dilution concentrate container valve 10g and the first main valve 10h. At the same time, the discharge may be fed to the feed side 2a. Then, pure water is extracted from the discharge on the feed side 2a to the dialysate concentrate on the draw side 2b via osmosis. Thus, the dialysate concentrate is diluted to form an intermediate dialysate, which is collected in the dilution concentrate container 32. This procedure may be called an FO session. Thus, the FO device 2 is configured to be used in an FO session for diluting the dialysate concentrate in the process of generating dialysate.
[0039] A liquid line 20i is provided 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 dilution dialysis concentrate pump 6 and the mixing unit 9. A water line 20n is provided between the pure water container 33 and the mixing unit 9 to connect the pure water container 33 and the mixing unit 9. The mixing unit 9 and the outlet connector P o To connect them, an outlet line 20m is used, and the mixing unit 9 and outlet connector P o It is positioned between the following. Exit connector P o It may be connected, for example, to a catheter in a PD patient, or to the dialysate line of an HD or CRRT device. The outlet valve 10m is positioned to work together with the outlet line 20m.
[0040] To mix the dialysate, the diluted dialysate in the diluted dialysate container 32 is delivered to the mixing unit 9 by opening the dilution concentrate container valve 10g, the second main valve 10k, and the outlet valve 10m, and using the diluted dialysate concentrate pump 6. Simultaneously, an osmotic agent or buffer solution such as glucose is delivered to the mixing unit 9 by a liquid solution pump (not shown). Pure water flows to the mixing unit 9 via the water line 20n. The main pump (not shown) provides the desired flow rate of dialysate obtained 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 diluted dialysate concentrate pump 6 and the liquid pump are controlled to achieve a specific rate in order to achieve a desired predetermined concentration of the dialysate based on the conductivity of the generated liquid, the conductivity of the diluted dialysate concentrate, and the flow rate of the generated liquid. In the mixing unit 9, the diluted dialysate concentrate, osmotic agent / buffer solution, and pure water are mixed in a mixing chamber (not shown) to form dialysate, and optionally heated. The dialysate is then discharged through the outlet line 20m to the outlet connector P o It is then delivered to the desired destination (e.g., a storage container or a dialysis machine).
[0041] Pure water typically meets the quality standards for water for injection (WFI) or water for dialysis (WFD). WFI has a maximum total organic carbon (TOC) of 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 and ISO 22519:2019.
[0042] Next, a method for evaluating the integrity of the FO membrane will be described with reference to the flowchart in Figure 3. This method is performed, for example, by the control unit 50 in Figure 2. The FO membrane is, for example, the FO membrane 2c of the FO device 2 in the apparatus 1 in Figure 2. However, the method may be used in other apparatuses that have an FO membrane for evaluating its integrity. This method may be performed before treatment is started or after treatment has been stopped. The method may also be started while treatment is in progress. Then, while the method is being performed, the production of dialysate is interrupted. In one embodiment, the method is performed at the feed inlet port E in S1 includes providing a flow of feed solution to the feed side 2a via E. In other words, the method includes passing the feed solution through the feed side 2a. Thus, the feed solution flows through the feed inlet port E. in Provided to, feed inlet port E in From there, it passes through the first side 2a for osmotic pressure exchange, through the FO membrane 2c, and to the outlet port E. out The solution flows through to the FO device 2, where it exits. The feed solution is, for example, drainage fluid or water. If the feed solution is drainage fluid, the feed pump 3 is used to open and close the appropriate valves and pass through the drainage fluid container 35, the patient, or the inlet connector P. i From other fluid sources connected to it, and furthermore, from the inlet port E of the first side 2a in This includes feeding the discharge liquid into the first discharge liquid inlet line 20a, for example, the inlet connector P. i This may include connecting to and using a feed pump 3 to send water to the feed side 2a. Providing S1 is the outlet port E of the first side 2a. outThe operation point of the apparatus 1 is typically well defined while providing a flow of feed solution S1. For example, the operation point includes providing a flow of feed solution at a constant, relatively high flow rate S1 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 measured by a flow sensor (not shown) and used as feedback for flow rate control at the feed pump 3. The operation point may also include providing hydrostatic pressure S1 to the feed side 2a. The hydrostatic pressure may simply be a result of providing a certain flow rate as described above. Alternatively, providing S1 may include controlling the hydrostatic pressure on the feed side 2a to a certain pressure, for example, a pressure close to atmospheric pressure or atmospheric pressure. The pressure is controlled, for example, using the feed pump 3 and / or valve 10e. The pressure on the feed side is measured using the pressure sensor 8 and can be used as feedback for pressure control by the feed pump 3 and / or the discharge outlet valve 10e.
[0043] The method is to draw the input port L in The method further includes providing a flow of the draw solution to the draw side 2b via S2. Providing a flow of the draw solution to the draw side 2b S2 may be carried out while providing a flow of the feed solution to the feed side 2a S1. In other words, the method includes passing the draw solution through the second side 2b. Thus, the draw inlet port L in The draw solution provided is for the draw inlet port L in From there, through the second side 2b for osmotic pressure exchange, and through the FO membrane 2c to the draw outlet port L out The solution flows through to the FO device 2, where it exits. The drawn solution is a dialysis concentrate, such as a dialysis concentrate. In the case of a dialysis concentrate, S2 provides the following: using the draw pump 5, the first main valve 10h and the dilution concentrate container valve 10g are closed, and the dialysis concentrate container 31 is drawn through the draw inlet port L on the second side 2b.in The method includes supplying a dialysis concentrate to the feed side. The draw solution has a higher osmotic pressure than the feed solution. Therefore, providing a flow of the draw solution S2 includes providing a flow of the draw solution having an osmotic pressure at feed side 2b that is higher than the osmotic pressure at feed side 2a. This extracts water from feed side 2a to draw side 2b and dilutes the draw solution. Therefore, the method includes diluting the draw solution and dehydrating the feed solution. The osmotic pressure of a solution is proportional to the molar concentration of solute particles in the solution. The solute particles in question may be electrolytes. Electrolytes are substances that conduct electricity when dissolved in water. In some embodiments, the draw solution has an osmotic pressure between 70 and 260 bar (10¹⁵ to 3770 psig). Therefore, the feed solution shall have an osmotic pressure of less than 70 bar (10¹⁵ psig), for example, less than 10 bar (145 psig), to provide an osmotic pressure difference between feed side 2a and draw side 2b. The discharged liquid may have an osmotic pressure of approximately 8 bar (116 psig). Water has a very low osmotic pressure, typically much lower than 1 bar (14.5 psig). Therefore, 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. Therefore, the hydrostatic pressures at the feed side 2a and the draw side 2b can be equal or close to equal in magnitude. The operating point of the apparatus 1 is typically well defined while providing a flow of the draw solution S2. For example, the operating point includes providing a flow of the draw solution at a constant flow rate S2 of the draw solution supplied to the draw side 2b. The flow rate supplied by the draw pump 5 is typically reduced via a dilution factor of the draw solution, e.g., 1:20. Therefore, the flow supplied by the draw pump 5 may be 20 times lower than the flow supplied by the feed pump 3. The flow rate is either directly controlled by the draw pump 5 or measured by a flow sensor (not shown) and used as feedback for flow rate control in the draw pump 5.
[0044] When flow is supplied to both sides 2a and 2b, the method is to supply flow through the draw inlet port Lin and feed inlet port E in Flow through, and feed exit port E out S3 includes stopping the flow through the draw inlet port L. In the apparatus 1 shown in Figure 2, this step is performed at the draw inlet port L in To stop the flow through, stop the draw pump 5, stop the feed pump 3, and stop the feed inlet port E in To stop the flow through the feed outlet port E, close the fourth discharge inlet valve 10d and the third discharge inlet valve 10c (or the second discharge inlet valve 10b), and close the feed outlet port E out This includes closing the discharge outlet valve 10e to stop the flow through the draw outlet port L. out The fluid remains connected to the dilution / concentration container 32. Therefore, the draw outlet port L outLiquids mediated through the fluid are acceptable. When the flow is stopped in step S3, the hydrostatic pressure in the dilution concentrate container 32 is assumed to be close to atmospheric pressure, e.g., 1013 hPa (approximately 1 bar, 14.5 psig). Since the draw side 2b and the dilution concentrate container 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 and obtaining 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 its maximum value. At this time, the osmotic pressure difference between the feed side 2a, the draw side 2b and the TMP is in equilibrium. Therefore, when the flow is stopped, there is no more inflow of new feed solution into the feed side 2a and no more inflow of new draw solution into the draw side 2b. However, the osmotic process continues. In this process, pure water moves from the feed side 2a to the draw side 2b through the FO membrane 2c, 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 dilution 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 dilution concentrate container 32. Therefore, TMP increases compared to the TMP when the flow is stopped in step S3. If a leak is present 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 osmosis process using water molecules. The osmosis process continues until TMP balances the osmotic pressure difference. Therefore, TMP is equal to the positive osmotic pressure difference (if TMP is defined as Pdraw-Pfeed). At this point, TMP has reached its maximum value since the flow was stopped in step S3, and therefore TMP has peaked. Here, TMP changes from a negative or zero TMP (when the flow is stopped) to a positive TMP. Therefore, the TMP peak is the peak of positive TMP. An example of a TMP curve with a TMP peak is shown in Figure 4, which is explained below.At the maximum value of TMP, the rate of TMP is zero. Therefore, the maximum value of TMP is also characterized by the relaxation rate of TMP, which has a magnitude of zero. In an ideal FO membrane 2 with integrity, TMP is kept fairly constant. However, most, if not all, FO membranes have a very small acceptable integrity error, which allows some solute to diffuse from the draw side 2b to the feed side 2a, causing TMP to decrease very slowly. Thus, TMP begins to relax. The liquid in the FO unit 2 strives to maintain equilibrium between the osmotic pressure difference and TMP. In an FO membrane with integrity error, it is expected that TMP will decrease fairly rapidly after it has peaked. The rapid decrease is because a larger integrity error causes greater diffusion of solute or leakage flow from the draw side 2b to the feed side 2a. Therefore, the progression of TMP during the period after it has peaked can be used as a basis for evaluating the integrity of the FO membrane 2. To understand how TMP progresses, TMP needs to be monitored. Therefore, the method includes monitoring one or more pressures that indicate the TMP S4. For example, monitoring S4 includes monitoring the pressure on the feed side 2a using a pressure sensor 8. Monitoring S4 includes repeatedly measuring the pressure on the feed side 2a. Monitoring S4 may also include determining the TMP from the pressure measured on the feed side 2a, assuming that the pressure on the draw side 2b is constant and close to atmospheric pressure, for example, less than 1 bar (14.5 psig). The TMP is well represented by the pressure measured on the feed side 2a, for example, the pressure measured by the pressure sensor 8. However, as the hydrostatic pressure on the feed side 2a decreases until it reaches the TMP peak, the TMP peak, and therefore the maximum value of the TMP, corresponds to when the hydrostatic pressure on the feed side 2a reaches its minimum value. Alternatively, the method also includes measuring the hydrostatic pressure on the draw side 2b. Monitoring S4 then includes repeatedly measuring the pressure on the draw side 2b. The method may include determining TMP as (hydrostatic pressure Pdraw at the draw side 2b) - (hydrostatic pressure Pfeed at the feed side 2a).In other words, monitoring S4 includes monitoring one or more pressures, including a pressure indicating the pressure on the feed side 2a, and / or monitoring one or more pressures, including a pressure indicating the pressure on the draw side 2b.
[0045] TMP provides a basis for evaluating the integrity of the FO film. In a first embodiment, the method includes evaluating the integrity of the FO film based on one or more pressures that indicate TMP S8. Thus, one or more parameters to be monitored include one or more pressures that indicate TMP. The characteristics of TMP provide a basis for evaluating the integrity of the FO film 2c. Thus, according to some embodiments, evaluating integrity S8 includes evaluating the characteristics of TMP or one or more pressures that indicate TMP, including one or more of magnitude, time to reach maximum value and / or relaxation. Evaluating S8 may be based on the achievement of one or more integrity criteria defined for the characteristics of TMP, for example, with respect to one or more of magnitude, time to reach maximum value and / or relaxation. The magnitude of TMP at its maximum value gives an indicator of whether the FO film has an integrity error. Also, the time it takes to reach maximum TMP after the flow has stopped indicates whether the FO film has an integrity error. While the maximum TMP is being constructed, an integrity error causes the transport of liquid from the draw side 2a to the feed side 2b, resulting in reaching the maximum TMP faster and / or at a lower level than would be possible without the integrity error. Therefore, evaluating integrity S8 may include determining and comparing the magnitude of the TMP at its maximum value with a predetermined magnitude of the TMP at its maximum value defined for an intact FO membrane (for equivalent liquids). Evaluating integrity S8 may also include determining the time required to establish the maximum TMP defined for an intact FO membrane and comparing it to the time required to establish the maximum TMP. If the difference is below a predetermined threshold, evaluation S8 may include determining that the FO membrane has sufficient integrity; otherwise, determining that the FO membrane lacks sufficient integrity. The threshold may be predetermined by experiment or calculation. After reaching the maximum TMP, the TMP aims to ease, and therefore, if the FO filter has an integrity error, the 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. Subsequently, the difference between the hydrostatic pressure on the feed side 2a and the hydrostatic pressure on the draw side 2b decreases.This means that the TMP decreases and therefore the TMP undergoes relaxation. In other words, assessing integrity S8 involves assessing the relaxation of the TMP based on one or more monitored pressures that indicate the TMP. Thus, the method involves monitoring one or more pressures for relaxation. Since the pressure is uncontrolled, the relaxation may be referred to as relaxation of the pressure difference between the free or uncontrolled feed side 2a and draw side 2b. The relaxation may be caused by either convective liquid transport from draw side 2b to feed side 2a, and therefore leak, or diffusive solute transport from draw side 2b to feed side 2a (diffusive water transport from draw side 2b to feed side 2a). The TMP relaxation rate and / or the properties of the TMP may be monitored. The greater the leak and / or diffusive transport, the greater the magnitude of the TMP relaxation rate. Thus, the relaxation rate is the time derivative or time gradient of the TMP. The relaxation rate indicates the pace at which the TMP is relaxing, and therefore the pace at which the hydrostatic pressure on the feed side 2a and the hydrostatic pressure on the draw side 2b are equalized. Accordingly, according to some embodiments, the method includes evaluating the integrity of the FO film 2c based on the magnitude of the relaxation rate of the TMP, which is determined based on one or more monitored pressures indicating the TMP. To evaluate the integrity of the FO film 2c, a specific integrity criterion may be applied to the magnitude of the relaxation rate. The integrity criterion may include one or more predetermined magnitude thresholds. The integrity of the FO film may be established by comparing the magnitude of the relaxation rate with one or more predetermined magnitude thresholds. One or more thresholds may be predetermined by, for example, experiment or calculation. In some embodiments, a first predetermined magnitude threshold defines a first upper limit on the size of an integrity FO film 2c, which sets a limit on the acceptable size. If the size is below or above the first upper limit, the evaluation includes determining that the FO film 2c is integrity. Therefore, the relaxation rate is very slow, exhibiting normal FO film characteristics (no leaks and expected / acceptable rates of solute diffusion). If the size exceeds the first upper limit, the evaluation includes determining that the FO film 2c has an integrity error. In some embodiments, a second predetermined size threshold defines a second upper limit on the size of an intact FO film 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 above 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 increase in electrolyte diffusion rate and / or less membrane leakage. 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 membrane leakage that allows for significant solute transfer of liquid from the draw side 2b to the feed side 2a and / or a higher increased rate of solute diffusion across the membrane. Thus, the method includes evaluating 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 over a period after the TMP peak, for example, the first 2 to 5 minutes after the TMP peak. In other words, according to some embodiments, evaluating the integrity of the FO film involves assessing integrity based on one or more monitored parameters, including one or more pressures indicating the TMP during the period after the maximum TMP has been achieved. The results may be communicated to the user via a user interface (not shown) of the control device 10, and / or an alarm may be triggered if an integrity error is detected. The user can then take appropriate action, such as replacing the FO device, if an integrity error has occurred.
[0046] Using the method described above, tests were conducted using a complete FO membrane (a sound FO membrane) and 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 and M) using the same FO membrane. The FO membrane used was aquaporin TMThe model is HFFO2 (Hollow Fiber Forward Osmosis 2). 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 intact FO membranes and two with a single fractured fiber. The FO session was performed using 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 a concentrate of the same concentrate diluted 1:20 to mimic the PD discharge on the feed side (50 ml / min) (corresponding to step S2 of the method). The FO session was abruptly stopped (corresponding to step S3 of the method) by stopping the pump at time t=0 and closing the discharge outlet valve 10e. Pressure was 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 obtained TMP is shown in Figure 4, where M1 and N1 represent the TMP peaks of an intact FO membrane, and M2 and N2 represent the state where one fiber was broken. Pdraw remained almost constant because the draw side was open to the liquid collector bag. Pfeed rapidly dropped as water was transported from the feed side to the draw side due to the remaining osmotic pressure difference, thereby increasing the TMP. In the intact FO membrane test, the TMP rose to approximately 300 mmHg (M1 and N1) and then slowly decreased during the 35-minute recording. When one fiber was manually broken, the TMP rapidly decreased after an initial rise of approximately 300 mmHg (M2) and approximately 280 mmHg (N2) in two different tests. The results strongly support that even small leaks significantly alter the TMP relaxation rate and therefore the method is sufficiently sensitive for automated integrity assessment.
[0047] In the second embodiment, the method includes the following additional steps S5-S7 after step S4. In this embodiment, the second embodiment includes determining the maximum value of TMP based on one or more monitored pressures indicating TMP. The maximum value of TMP corresponds to TMP when it has a relaxation velocity of zero magnitude after the flow is stopped in step S3. As described, when TMP is at its maximum value, the hydrostatic pressure at the feed side 2a is at its minimum value. Therefore, the method may include determining the maximum value of TMP as the TMP value with a relaxation velocity of zero magnitude that occurs at the same time as the hydrostatic pressure at the feed side 2a reaches its minimum value. Based on one or more monitored pressures indicating TMP and the determined maximum value of TMP, the method adjusts the feed inlet port E so that TMP corresponds to the determined maximum value of TMP. in or feed exit port E out S6 further includes controlling the flow of solution via the feed inlet port E, for example, depending on which pump is used for control. in or feed exit port E out It is permitted through either of the following. The method includes comparing the TMP after the maximum TMP is achieved with the maximum value of the determined TMP, and eliminating the difference between them 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 done by controlling the speed of the pump. In the embodiment of Figure 2, controlling S6 includes controlling the speed of the feed pump 3. If there is an integrity issue, as mentioned above, it is expected that the liquid will be transported from the draw side 2b to the feed side 2b, and then the TMP will decrease. To maintain the TMP at the determined maximum TMP, the method controls the feed pump 3 to transport the liquid from the feed side 2a to the feed inlet port E of the discharge container 35. in This includes feeding liquid through the feed outlet valve 10e. The discharge outlet valve 10e remains closed. Instead, the liquid is fed from the feed side 2a to the feed outlet port E outAnother pump (not shown) may be provided to drain through the valve. The discharge outlet valve 10e is then opened and the feed pump 3 remains stopped. The integrity can be assessed by monitoring the results of the control in step S6, such as parameters that are the resulting flow rate, the resulting pump speed, or the resulting power to the pump. Thus, the method includes monitoring one or more parameters that indicate the flow rate of the resulting flow of the solution in S7. In some embodiments, monitoring S7 includes monitoring the speed of the feed pump 3. The pump speed is already available in the control device 10 as it is a control parameter for 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 control device 10. The power to the pump, and therefore the power, current, or voltage used by the pump, is also a control parameter available in the control device 10.
[0048] The method according to the second embodiment further includes evaluating the integrity of the FO membrane 2c based on one or more monitored parameters indicating the flow rate of the resulting solution flow S8. Here, the evaluation is based on parameters such as the characteristics of the resulting feed solution flow, e.g., the resulting flow rate of the solution from the feed side, the pump speed, or the power used by the pump. A specific integrity criterion may be applied to one or more monitored parameters to evaluate the integrity of the FO membrane 2c. Thus, a specific integrity criterion may be used to determine the integrity of the FO membrane 2c from one or more monitored parameters. The integrity criterion may include one or more predetermined parameter thresholds. The integrity of the FO membrane may be established by comparing the parameters with one or more predetermined parameter thresholds. One or more thresholds may be predetermined, for example, by experiment or calculation. In some embodiments, a first predetermined threshold defines a first upper limit on the parameter values of an FO membrane 2c that has integrity. If the parameter value is less than or equal to the first upper limit, the evaluation includes determining that the FO membrane 2c has integrity. For example, if it is not necessary to remove liquid from the feed side 2a to control the TMP to a desired TMP, the FO membrane 2c is intact. Here, the resulting flow rate, velocity, 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, velocity, or power exceeds its first upper limit, the method includes determining that the FO membrane 2c has an integrity error. As is understood, certain types of parameters are compared to thresholds or limits of the same type. In some embodiments, a second threshold of a predetermined size defines a second upper limit for the parameter values of an intact FO membrane 2c. 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 after the TMP peak, for example, the first 2 to 5 minutes after the TMP peak.Therefore, the method includes assessing integrity based on the achievement of one or more integrity criteria of one or more parameters indicating the flow rate of the resulting flow from the feed solution S8.
[0049] In the alternative configuration described above, the tested direction of solute transfer (leak) is from the draw side 2b to the feed side 2a, which is of less interest from a risk perspective than the opposite direction. Nevertheless, evaluation is appropriate for leaks that allow for solute selectivity and leakage in both directions. However, solute transfer from the feed side 2a to the draw side 2b is important because it carries the risk, for example, of transporting patient effusion to the liquid production side, thereby altering the composition of the resulting fluid. Due to the possibility that the leak may act as a backflow valve, allowing only unidirectional leakage, the alternative configuration described above can be complemented by a method step for testing solute transfer from the feed side 2a to the draw side 2b. To test solute transfer from the feed side 2a to the draw side 2b, the bulk pressure difference (Pfeed > Pdraw) from the feed side 2a to the draw side 2b is established by controlling the feed side pump, e.g., feed pump 3, while monitoring the feed side pressure with a pressure sensor 8 and monitoring the relief pressure. Therefore, the method includes temporarily increasing the hydrostatic pressure on the feed side 2a S9. The increase is performed after the tested directions from the draw side 2b and the feed side 2a have been performed, and therefore after step S8 has been reached. The temporal increase requires that the hydrostatic pressure on the feed side 2a increases compared to the hydrostatic pressure on the draw side 2b. Then, TMP first becomes zero, and then increases in the opposite direction compared to the direction of TMP at the maximum TMP described earlier. When the feed side pressure rises to a certain level, e.g., 300 mmHg, the feed pump 3 is stopped (thus the feed inlet port E in Step S10 is performed, which includes stopping the flow through the draw inlet port L. in Flow and feed outlet port E outThe flow through is also stopped in the same manner. Here, the same steps S4 and S8, and possibly S4 to S8, are repeated so that the TMP gradient is evaluated or maintained by feeding in a TMP with a gradient of zero using the feed pump 3, the only difference being that the evaluation evaluates the integrity error caused by leakage from the feed side 2a to the draw side 2b. Thus, in some embodiments, the method is to (i) increase the hydrostatic pressure at the feed side 2a after performing step S8 so that it is greater than the hydrostatic pressure at the draw side 2b, and (ii) feed inlet port E in (ii) stopping the flow through S10, and (ii) a method including repeating steps S4 and S8, or S4 to S8.
[0050] This disclosure also relates to a control device 10 for evaluating the integrity of the FO membrane 2c of a forward osmosis (FO) device 2 in a dialysate generating device 1. The FO membrane 2c separates the feed side 2a and the draw side 2b of the FO device 2. The control device 10 controls the feed inlet port E in A feed pump 3 is configured to provide a flow of feed solution to the feed side 2a via the feed side 2a, and the osmotic pressure of the draw side 2b is higher than the osmotic pressure of the feed side 2a, and the draw inlet port L in The control device 10 also includes a draw pump 5 configured to provide a flow of draw solution to the draw side 2b via the feed side 2a, thereby enabling the extraction of water from the feed side 2a to the draw side 2b and diluting the draw solution. The control device 10 also includes one or more pressure sensors 8 configured to measure one or more pressures indicating the TMP between the draw side 2b and the feed side 2a, and a valve device 20 configured to control one or more flows via the draw inlet port, the feed inlet port, or the feed outlet port. The control device 10 uses the feed pump 3, the draw pump 5, and the valve device 10 to control the draw inlet port E in Flow via feed inlet port L in Flow through, and feed exit port E outThe flow through the membrane is stopped, thereby allowing water to continue to be extracted from the feed side 2a to the draw side 2b until the transmembrane pressure difference (TMP) between the draw side 2a and the feed side 2b reaches its maximum value. The control device 10 is further configured to monitor one or more pressures indicating the TMP using one or more pressure sensors 8, and to evaluate the integrity of the FO membrane based on 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 a method according to any one of the embodiments described herein.
[0052] While the present invention has been described in relation to what is currently considered the most practical and preferred embodiment, it should be understood that the present invention is not limited to the disclosed embodiment, but rather is intended to encompass various modifications and equivalent configurations included within the scope of the appended claims.
Claims
1. A method for evaluating the integrity of the FO membrane (2c) of a forward osmosis (FO) device (2) in a dialysate generating apparatus (1), wherein the FO membrane (2c) separates the feed side (2a) and the draw side (2b) of the FO device (2), and the FO device (2) comprises a feed inlet port (Ein) and a feed outlet port (Eout) that are in fluid communication with the feed side (2a), and a draw inlet port (Lin) and a draw outlet port (Lout) that are in fluid communication with the draw side (2b), and the method is as follows: Providing a flow of feed solution to the feed side (2a) via the feed inlet port (Ein) (S1), The method involves providing a flow of the draw solution to the draw side (2b) via the draw inlet port (Lin) at an osmotic pressure higher on the draw side (2b) than on the feed side (2a) (S2), thereby extracting water from the feed side (2a) to the draw side (2b) and diluting the draw solution. (S3) stopping the flow through the draw inlet port (Lin), the flow through the feed inlet port (Ein), and the flow through the feed outlet port (Eout), As a result, water continues to be extracted from the feed side (2a) to the draw side (2b) until the intermembrane pressure difference (TMP) between the draw side (2b) and the feed side (2a) reaches its maximum value. Monitoring one or more pressures indicating the TMP (S4), A method comprising (S8) evaluating the integrity of the FO film based on one or more monitored parameters, including one or more pressures indicating the TMP.
2. The method according to claim 1, wherein evaluating the integrity (S8) is, A method comprising evaluating the characteristics of the TMP or one or more pressures exhibiting the TMP, including one or more of the following: magnitude, time to reach a maximum value, and / or relaxation.
3. A method according to claim 2, comprising evaluating the integrity of the FO film (2c) based on the magnitude of the relaxation rate of the TMP, which is determined based on the monitored pressures indicating the TMP (S8).
4. A method according to claim 3, comprising evaluating the integrity of the TMP on the basis of achieving one or more integrity criteria for the magnitude of the relaxation rate of the TMP (S8).
5. A method according to claim 1, wherein evaluating the integrity of the FO film (S8) comprises evaluating the integrity based on one or more monitored parameters, including the one or more pressures indicating the TMP during the period after the stopping (S3) has been performed.
6. A method according to claim 1, wherein the maximum value of the TMP is characterized by a relaxation rate of the TMP having a magnitude of zero.
7. The method according to claim 1, wherein the method is Based on the one or more monitored pressures indicating the TMP, the maximum value of the TMP is determined (S5), Based on the monitored pressures indicating the TMP and the determined maximum value of the TMP, control the flow of the solution through the feed inlet port (Ein) or the feed outlet port (Eout) so that the TMP corresponds to the determined maximum value of the TMP (S6), A method comprising monitoring (S7) one or more parameters indicating the flow rate of the solution obtained as a result of the control (S6).
8. The method according to claim 7, The aforementioned control (S6) includes controlling the speed of the feed pump (3), The monitoring (S7) includes monitoring the speed of the feed pump (3), A method comprising evaluating the integrity (S8) of the FO membrane (2c) based on the monitored speed of the feed pump (3).
9. A method according to claim 7, comprising evaluating the integrity (S8) based on the achievement of one or more integrity criteria of one or more parameters indicating the flow rate of the solution obtained as a result of controlling (S6).
10. A method according to claim 1, wherein the draw outlet port (Lout) is connected to a dilution concentrate container (32).
11. A method according to claim 1, wherein the monitoring (S4) includes monitoring one or more pressures including a pressure indicating the pressure on the feed side (2a) and / or monitoring one or more pressures including a pressure indicating the pressure on the draw side (2b).
12. A method according to claim 1, comprising increasing the hydrostatic pressure on the feed side (2a) to be greater than the hydrostatic pressure on the draw side (2b) (S9), and the feed inlet port (E ｉｎ A method comprising stopping the flow through (S4), monitoring one or more pressures indicating the TMP, and evaluating the integrity of the FO film based on one or more monitored parameters, including the one or more pressures indicating the TMP (S8).
13. A control device (10) for evaluating the integrity of the FO membrane (2c) of a forward osmosis (FO) device (2) in a dialysate generating apparatus (1), wherein the FO membrane (2c) separates the feed side (2a) and the draw side (2b) of the FO device (2), the FO device (2) comprises a feed inlet port (Ein) and a feed outlet port (Eout) that are in fluid communication with the feed side (2a), and a draw inlet port (Lin) and a draw outlet port (Lout) that are in fluid communication with the draw side (2b), and the control device (10) A feed pump (3) is configured to provide a flow of feed solution to the feed side (2a) via the feed inlet port (Ein), A draw pump (5) provides a flow of the draw solution to the draw side (2b) via the draw inlet port (Lin) at an osmotic pressure higher on the draw side (2b) than on the feed side (2a), thereby enabling the 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 indicating TMP between the draw side (2b) and the feed side (2a), The system includes 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) The feed pump (5), the draw pump (5), and the valve device (10) are used to stop 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), thereby allowing water to continue to be extracted from the feed side (2a) to the draw side (2b) until the intermembrane pressure difference (TMP) between the draw side (2a) and the feed side (2b) reaches its maximum value. One or more pressures indicating the TMP are monitored using one or more pressure sensors (8) as described above. A control device configured to evaluate the integrity of the FO film based on one or more monitored parameters, including one or more pressures indicating the TMP.
14. A control device (10) according to claim 13, wherein the control device is configured to perform the method described in any one of claims 1 to 12.
15. A solution generating device (1) for generating dialysate, wherein the solution generating device (1) comprises a forward osmosis (FO) device (2) including an FO membrane (2c) that separates the feed side (2a) and the draw side (2b) of the FO device (2), and the solution generating device further comprises a control device (10) according to claim 13.