Production of medical fluids for renal replacement therapy

Abstract

A system for producing a medical fluid for renal replacement therapy is operated by a control device according to a method, in which a first pump (P1) is operated to convey a first fluid (F1) from a first container (3a) arranged on a first scale (2a) to a supply path (4a) and a second pump (P2) is operated to convey a second fluid (F2) from a second container (3b) arranged on a second scale (2b) to the supply path (4a) to produce a mixture therein. The speed of at least one of the pumps (P1, P2) is adjusted until a sensor (22) measures a target value of a composition-related parameter. A relationship between the weight changes of the first and second scales (2a, 2b) is determined while the sensor (22) measures the target value. A medical fluid is then produced in the supply path (4a) by operating the pumps (P1, P2) based on signals (S1, S2) from the scales (2a, 2b) to achieve said relationship. The supply path (4a) may be disposable and the sensor (22) may be reusable and located in the bypass path (20).

Description

[Technical field]

[0001] FIELD OF THE DISCLOSURE The present disclosure relates to the field of renal replacement therapy, and in particular to the production of medical fluids for use in such therapy. [Background technology]

[0002] Renal replacement therapy (RRT) is a therapy that replaces the normal blood filtering function of the kidney. It is used when the kidneys are not functioning adequately, including acute kidney injury (AKI) and chronic kidney disease (CKD), known as renal failure. RRT involves the removal of water from the blood of a patient suffering from renal failure, as well as the exchange of solutes with the blood. One example of RRT is extracorporeal blood therapy, in which blood is circulated outside the patient's body and interacts with one or more medical fluids. Modalities of extracorporeal blood therapy include hemodialysis (HD), hemofiltration (HF), and hemodiafiltration (HDF). Another example of RRT is peritoneal dialysis (PD), in which a medical fluid is infused into the patient's peritoneal cavity to interact with the patient's blood via the peritoneal membrane.

[0003] The medical fluid used in HD and PD is commonly known as dialysate. In HF, the medical fluid is known as replacement fluid because it is infused into the patient's blood to replace the fluid removed during treatment. In HDF, both dialysate and replacement fluid are used.

[0004] Extracorporeal blood therapy by HD, HF or HDF is performed differently for the treatment of patients with AKI compared to those with CKD by the use of different types of dialysis machines. Generally, AKI patients are treated continuously with lower fluid flow rates for longer periods of time compared to CKD patients. Such continuous treatment is commonly known as Continuous Renal Replacement Therapy (CRRT). To ensure accurate and consistent monitoring and control of fluid removal, known as ultrafiltration, AKI machines typically include scales that are used to measure the weight of fresh therapy fluid during treatment and the weight of used therapy fluid. CKD machines instead use flow meters or volumetric pumping to control ultrafiltration.

[0005] The PD machine, also known as a cycler, can include at least one scale for measuring the weight of fresh therapeutic fluid infused into the peritoneal cavity and the weight of spent therapeutic fluid withdrawn from the peritoneal cavity.

[0006] Over time, RRT consumes large amounts of medical fluids. In some modalities of RRT, premade medical fluids are delivered to the medical site in prefilled bags. For example, conventional PD is performed by the use of prefilled bags. AKI devices are configured to use prefilled bags of medical fluids by placing the prefilled bag on one of the scales before treatment and replacing the prefilled bag as needed. On the other hand, CKD devices have an integrated capability to generate medical fluids on demand, so-called online fluid generation, by mixing one or more concentrates with water. Recently, PD devices have been proposed with an integrated capability of online fluid generation.

[0007] The use of large amounts of medical fluids has a significant environmental impact through the large amount of plastic material consumed for transporting and manufacturing pre-filled bags. In intensive care units, the management and handling of pre-filled bags at the point of care is imposed on staff, taking time and diverting staff attention from other tasks. Therefore, there is a general need for AKI devices to enable online generation of medical fluids, preferably without the need to replace existing AKI devices. Summary of the Invention

[0008] SUMMARY OF THE PRESENT EMBODIMENT It is an object of the present invention to at least partially overcome one or more of the limitations of the prior art.

[0009] A further object is to enable on-line production of medical fluids by dialysis machines with multiple scales.

[0010] One or more of these objects, as well as further objects that may become apparent from the following description, are achieved at least in part by a method for generating a medical fluid for renal replacement therapy, a control device, a computer readable medium, a system for generating a medical fluid, and a disposable device, embodiments of which are defined by the dependent claims.

[0011] A first aspect is a computer-implemented method of producing a medical fluid for renal replacement therapy, the method including operating a first pump to convey a first fluid from a first container disposed on a first scale into a supply path extending to an outlet for the medical fluid, operating a second pump to convey a second fluid from a second container disposed on a second scale into the supply path to produce a mixture of the first and second fluids in the supply path, measuring a composition-related parameter of the mixture with a sensor, and adjusting a pumping speed of at least one of the first and second pumps until the sensor measures a target value of the composition-related parameter. The method further includes determining a relationship between a first weight change on the first scale and a second weight change on the second scale while the sensor is measuring the target value based on first and second output signals from the first and second scales, and producing the medical fluid in the supply path. The generating includes operating the first pump and the second pump based on the first output signal and the second output signal to achieve the relationship between the first weight change and the second weight change.

[0012] A second aspect is a controller comprising circuitry configured to perform the method of the first aspect and a signal interface configured to output control signals for the first pump and the second pump, the signal interface further configured to receive the first and second output signals from the first and second scales and a sensor signal representative of the composition-related parameter from the sensor.

[0013] A third aspect is a computer-readable medium comprising computer instructions that, when executed by a processor, cause the processor to perform a method according to the first aspect.

[0014] A fourth aspect is a system for generating a medical fluid for renal replacement therapy, the system comprising a first scale, a first container disposed on the first scale, a second scale, and a second container disposed on the second scale, the system further comprising a supply path configured to receive a first fluid from the first container and a second fluid from the second container and extend to an outlet for the medical fluid, a first pump disposed to convey the first fluid from the first container to the supply path, a second pump disposed to convey the second fluid from the second container into the supply path to generate a mixture of the first and second fluids in the supply path, a sensor configured to measure a composition-related parameter, and the controller of the second aspect.

[0015] A fifth aspect is a disposable device for use in the system of the fourth aspect, the disposable device comprising a first container, the supply path, and a connection line in fluid communication with the supply path and extending to a first end fluid connector configured to connect to the second container, the disposable device further comprising a bypass path extending from the supply path to a second end fluid connector configured to connect to an inlet connector in fluid communication with the sensor.

[0016] Further objects and aspects, as well as embodiments, features, and technical advantages, may become apparent from the following detailed description, the appended claims, and the drawings. [Brief description of the drawings]

[0017] [Figure 1] FIG. 1 is a schematic diagram of an exemplary system for dialysis treatment. [Figure 2A] 2A-2B are schematic diagrams of a disposable device and mechanical components, respectively, for use in the system of FIG. [Figure 2B] Same as above [Figure 3A]3A-3B show the system of FIG. 1 during ongoing treatment and at an intermediate renewal stage, respectively. [Figure 3B] Same as above [Figure 4] FIG. 4 is a flow chart of an exemplary method for performing fluid control in the system of FIG. [Figure 5A] 5A-5B show the system of FIG. 1 during first and second preparatory steps, respectively, in the method of FIG. [Figure 5B] Same as above [Figure 6] 6-7 show modifications of the system of FIG. [Figure 7] Same as above [Figure 8] FIG. 8 is a flow chart of an exemplary method of operating the system of FIG. [Figure 9] FIG. 9 is a schematic diagram of an exemplary water dispenser with a reusable sensor. [Figure 10A] 10A-10B are side views of a reusable sensor before and after operation of a disposable line configured to contain fluid within the sensor. [Figure 10B] Same as above [Figure 11] FIG. 11 is a flow chart of an exemplary procedure for performing fluid control during interruptions in dialysis therapy. [Figure 12] FIG. 12 is a schematic diagram of an exemplary system for generating medical fluids. [Figure 13A] 13A-13B are a flow chart of an exemplary procedure for using an auxiliary sensor. [Figure 13B] Same as above DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0018] DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS The embodiments will now be described more fully hereinafter with reference to the accompanying drawings, in which some, but not all, embodiments are shown. Indeed, the subject matter of this disclosure may be embodied in many different forms and should not be construed as limited to the embodiments set forth herein, but rather, these embodiments are provided so that this disclosure will satisfy applicable legal requirements. Like reference characters refer to like elements throughout.

[0019] It will also be understood that, where possible, any of the advantages, features, functions, apparatus, and / or operational aspects of any of the embodiments described and / or contemplated herein can be included in any of the other embodiments described and / or contemplated herein, and / or vice versa. Furthermore, where possible, any term expressed in the singular herein is meant to include the plural and / or vice versa, unless expressly stated otherwise. As used herein, "at least one" means "one or more," and these phrases are intended to be interchangeable. Thus, the terms "a" and / or "an" shall mean "at least one" or "one or more," although the phrases "one or more" or "at least one" are also used herein. As used herein, unless the context otherwise requires to express the words or necessary implication, the words "comprise" or variations such as "comprises" or "comprising" are used in an inclusive sense, i.e., to specify the presence of the stated features, but not to preclude the presence or addition of further features in various embodiments.

[0020] Furthermore, it should be understood that although terms such as first, second, etc. may be used herein to describe various elements, these elements should not be limited by these terms. These terms are used only to distinguish one element from another. For example, a first element can be referred to as a second element, and similarly, a second element can be referred to as a first element, without departing from the scope of the present disclosure. As used herein, the terms "plurality," "multiple," and "plurality" are intended to mean the provision of two or more elements. The term "and / or" includes any and all combinations of one or more of the associated listed elements.

[0021] Well-known functions or structures may not be described in detail for brevity and / or clarity.Unless otherwise defined, all terms (including technical and scientific terms) used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs.

[0022] The present disclosure relates to techniques for online generation of medical fluids used in renal replacement therapy (RRT). As used herein, RRT refers to any therapy that replaces or supplements the normal hemofiltration function of a patient's kidneys. RRT may involve the removal of water from the patient's blood as well as the exchange of solutes with the blood. Techniques for online fluid generation are illustrated below with reference to hemodialysis (HD) but are applicable to any modality of either extracorporeal blood therapy or peritoneal dialysis (PD).

[0023] As used herein, online fluid generation refers to the on-site generation of medical fluids by mixing various components in the appropriate proportions. Online fluid generation can include on-demand fluid generation, where the rate of production of the medical fluid is adjusted to match the rate of consumption of the medical fluid, for example, by an ongoing RRT. It is also contemplated that online fluid generation can be performed independently of the rate of consumption of the medical fluid, for example, by providing the generated medical fluid to a storage container or reservoir.

[0024] The medical fluid may be any fluid consumed as part of RRT, also referred to as a "treatment fluid". In the context of extracorporeal blood therapy, the medical fluid may be a dialysate that interacts with the blood in a filtration unit commonly known as a "dialyzer". Alternatively or additionally, the medical fluid may be a so-called replacement fluid or fluid, which is injected into the blood upstream or downstream of the dialyzer, for example as part of hemofiltration (HF) or hemodiafiltration (HDF), as is well known in the art. In the context of PD, the medical fluid may be a dialysate that is injected into the patient's peritoneal cavity and interacts with the patient's blood through the peritoneal membrane lining the peritoneal cavity.

[0025] Medical fluids for use in RRT have a well-defined composition, which is tailored to a particular treatment and patient. In on-line generation, the composition of the medical fluid may be given by medical guidelines and / or set by a caregiver for a particular patient or group of patients. Medical guidelines may also define the allowable deviations from nominal concentrations of various solutes in the medical fluid.

[0026] As used herein, a "disposable device" (or part / device / sensor, etc.) is a device that is intended to be used for only a limited amount of time, after which the device is replaced with a new disposable device. Depending on the disposable device, the limited time may correspond to a single treatment session or a predetermined number of treatment sessions, or may be given by a predetermined maximum period of time. In another alternative, the disposable device may be replaced whenever a new patient is treated.

[0027] As used herein, a "reusable device" (e.g., a sensor) is a device that has a longer operational life than a corresponding device that is disposable. In some embodiments, a reusable device is not intended to be replaced at all; thus, at least in theory, its operational life is infinite. After all, such devices are often referred to as "permanent" or "permanently installed," although the device is replaced if it is deemed to be malfunctioning.

[0028] As used herein, a "treatment session" or "session" refers to the period during which a patient receives RRT through the use of a dialysis machine. This session begins when the patient is connected to the dialysis machine and ends when the patient is disconnected from the dialysis machine.

[0029] In the technique proposed herein, a medical fluid is produced as a mixture of two or more constituent fluids. The constituent fluids are provided from respective containers placed on respective scales. The technique is based on the insight that it may be advantageous to control the supply of the constituent fluids based on a measurement signal from the scale. Such control is possible if the mixing ratio of the constituent fluids is known. Although the mixing ratio may be theoretically determined based on the nominal composition of the constituent fluids, the use of a theoretical mixing ratio may introduce unacceptable deviations in the composition of the medical fluid, for example, if the actual composition of the constituent fluid deviates from its nominal composition or if the wrong constituent fluid is placed on the scale in the dialysis machine. Thus, the use of a theoretical mixing ratio may require strict tolerances for the composition of the respective constituent fluids and may require the implementation of special measures to prevent human errors when placing the containers on the scale.

[0030] An alternative approach is to control the supply of the respective constituent fluids based on a feedback signal generated by a sensor configured to measure a composition-related parameter (CRP) of the medical fluid, e.g., the conductivity. Such a CRP sensor is therefore placed in the main flow path for the medical fluid upstream of the dialyzer and provides continuous feedback on the current value of the CRP while the medical fluid is being generated. This approach is often used in CKD devices with integrated capabilities of online fluid generation, as discussed in the background chapter. One drawback of this approach is that the CRP sensor needs to be thoroughly disinfected intermittently, e.g., after each treatment session. As the CRP sensor is placed in the main flow path for the medical fluid, it is essential to prevent microorganisms from growing in the CRP sensor, because such microorganisms could be introduced into the medical fluid and harm the patient. To eliminate the need for disinfection, the CRP sensor may instead be installed as a disposable unit, which is discarded after use, e.g., after each treatment session. However, this significantly increases the cost of the treatment. For example, a conductivity sensor of sufficient accuracy is very expensive.

[0031] All of these drawbacks would be overcome if the mixing could be controlled instead based on the measurement signals from the scales, taking into account the mixing ratio. The technique proposed herein derives mixing control data (MCD) by the use of a CRP sensor in a configuration described below. The MCD takes into account the actual composition of the constituent fluids and specifies the desired relationship between the measurement signals from the scales. Thereby, the MCD replaces the theoretical mixing ratio and removes the associated drawbacks. At the same time, by using an ingenious adjustment procedure to derive the MCD, the need for intermittent replacement of the CRP sensor is also eliminated. As described in more detail below, the adjustment procedure involves directing a mixture of the two constituent fluids from their respective containers on the respective scales through the CRP sensor, while adjusting the feed rate of at least one of the constituent fluids. When the CRP sensor measures a target value corresponding to the desired mixing ratio between the constituent fluids, a current relationship between the weight changes on the scales is determined. The adjustment procedure can be repeated for further constituent fluids, if included in the medical fluid, resulting in a set of relationships that result in the desired mixing ratio of the constituent fluids in the medical fluid. When the medical fluid is generated and provided for use in the RRT, the supply of the make-up fluid is controlled to achieve a relationship between the weight change of the scale, thereby essentially generating a medical fluid having a desired composition. Because the supply of the make-up fluid is controlled based on the measurement signal from the scale, there is no need for continuous feedback from the CRP sensor while the medical fluid is being generated. This measure allows the CRP sensor to be positioned such that it is exposed only to the make-up fluid during the conditioning process. In other words, the medical fluid provided for use in the RRT does not have to pass through the CRP sensor and is therefore not exposed to any microorganisms that may be present in the CRP sensor. This reduces the need for intermittent disinfection of the CRP sensor as well as the need to intermittently replace the CRP sensor. Furthermore, by limiting exposure to the medical fluid, fouling of the CRP sensor is reduced, for example in terms of scaling. This extends the operational life of the CRP sensor and may even allow the use of permanently installed CRP sensors. Since CRP sensors are generally expensive, significant cost savings are possible.

[0032] As mentioned in the Background section, commercially available dialysis machines used to treat acute kidney injury (AKI) typically include scales to control dialysis flow parameters. As will be understood below, such existing dialysis machines can be simply reconfigured to use the techniques proposed herein. Thus, dialysis machines designed to use pre-made bags of medical fluid can be converted to generate medical fluid online. Of course, it is also contemplated that novel dialysis machines can be developed to utilize the techniques proposed herein for use in any modality of extracorporeal blood therapy or PD.

[0033] Various embodiments will now be described with reference to FIG. 1, which shows an exemplary system 1 for dialysis treatment, specifically a system for extracorporeal blood therapy by hemodialysis. The system 1 is configured to generate on demand a dialysis fluid for use in hemodialysis. The system 1 comprises scales 2a-2d configured to provide respective measurement signals S1-S4 representative of mass. The containers 3a-3d are arranged on the respective scales 2a-2d. Instead of being suspended from the scales 2a-2d as shown, the containers 3a-3d may be arranged to rest on the scales 2a-2d. The containers 3a-3d may be rigid or flexible and may be of any material, for example plastic. In the illustrated example, the dialysis fluid is generated by mixing three fluids F1, F2, F3 ("constituent fluids"). The first fluid F1 in the first container 3a is water, and the second and third fluids F2, F3 in the second and third containers 3b, 3c are different liquid concentrates. For example, the concentrates may be so-called A and B concentrates, as known in the art. In the following, it will be assumed that F2 is the A concentrate and F3 is the B concentrate, but vice versa is also possible. The system 1 further comprises a pumping apparatus comprising pumping devices ("pumps") P1-P6. Each pump P1-P6 may be of any type. In cases where the fluid paths in the system are defined by disposable devices (hereinafter), the pumps P1-P6 are typically peristaltic pumps, which engage the outside of dedicated tubing. The pumps P1-P6 operate in response to control signals C1-C6.

[0034] The first fluid line 4a extends from the first container 3a to the dialyzer 7 and forms a main supply path for the dialysate. The second fluid line 4b extends from the second container 3b to a first junction 6' on the first fluid line 4a, and the third fluid line 4c extends from the third container 3c to a second junction 6'' downstream of the first junction 6' on the first fluid line 4a. The system 1 is configured to allow a flow of F2 to meet with a flow of F1 in the junction 6' and downstream in the first fluid line 4a to form a mixture. Similarly, the system 1 is configured to allow a flow of F3 to meet with a combined flow of F1 and F2 in the junction 6' and downstream in the first fluid line 4a to form a mixture. The mixing of F1 and F2 may or may not be completed at the junction 6'', and the mixing of F1, F2, and F3 is completed at the outlet from the first fluid line 4a, i.e., upon entry into the dialyzer 7. In the illustrated example, pump P1 is disposed in the first fluid line 4a to define the flow rate of dialysate (the "main flow rate"), and pumps P2, P3 are disposed in the second and third fluid lines to define the flows of F2, F3, respectively. Thus, pumps P2, P3 are operable to control the amount of F2, F3 mixed with F1 in the first fluid line 4a.

[0035] Although not shown in FIG. 1 , system 1 can include one or more devices configured to enhance mixing, for example, within each junction 6′, 6″. In some embodiments, each junction 6′, 6″ is a three-way connector. Non-limiting examples of three-way connectors with mixing enhancement devices are disclosed in WO 2009 / 030973, which is incorporated herein by reference. In a variant, the mixing enhancement device may be separate from and located downstream of junction 6′, 6″. Such a separate device may be configured to increase at least one of the Reynolds number of the mixture and / or the flow of the incoming fluid. Alternatively, the separate device may be configured as a conventional static mixer or a recirculation circuit that enhances mixing before the mixture is circulated and delivered to the dialyzer 7.

[0036] The dialyzer 7 is a conventional blood filter, with a semi-permeable membrane 7' arranged to define a first chamber for dialysate and a second chamber for blood. One end of the first chamber is connected to receive dialysate from a first fluid line 4a. The dialysate flows through the first chamber and exits the dialyzer 7 at the opposite end. The dialysate exiting the dialyzer 7 is "spent". To distinguish fresh dialysate from spent dialysate, the latter is herein denoted as "effluent" and referred to as EF. The second chamber of the dialyzer 7 is arranged to receive blood from a draw line 8a connected to a subject 10 by a connector 9a. Typically, the subject 10 is a dialysis patient, and the connector 9a is an access device (catheter, needle, etc.) in fluid communication with the patient's circulatory system. However, it is also conceivable that the subject 10 is a reservoir of blood to be treated. The second chamber is also in fluid communication with a return line 8b, which extends to a connector 9b connected to the subject 10. A pump P5 is disposed along the withdrawal line 8a and pumps blood from the subject or patient 10 back to the subject 10 through the withdrawal line 8a, the second chamber, and the return line 8b. When passing through the second chamber, the blood is connected with the dialysate through the membrane 7' and is thereby treated by hemodialysis. The principles of hemodialysis are well known to those skilled in the art and will not be further described herein. It should be understood that the example of FIG. 1 is simplified and may include further conventional components such as clamps, pressure sensors, air detectors, etc.

[0037] In the example of FIG. 1, the first chamber of the dialyzer 7 is fluidly connected to an effluent line 12 that extends to a fourth container 3d. A pump P4 is disposed along the effluent line 12 for pumping EF from the dialyzer 7 into the container 3d. The container 3d is further fluidly connected to a drain line 14. The drain line 14 is part of a drain path that extends to a drain 16. A pump P6 is disposed along the drain line 14 for pumping EF from the container 3d to the drain 16. The pump P6 is operable to completely or at least partially evacuate the container 3d during an evacuation phase. As described below, the evacuation phase can be selectively initiated when the container 3d is considered to be (sufficiently) full.

[0038] In the illustrated example, the drain path comprises the drain line 14, an adjacent line segment 20b connected to the sensor 22, and a further adjacent line segment 20c extending from the sensor 22 to the drain 16. The sensor 22 is configured to measure a composition-related parameter (CRP) of the passing fluid. The CRP can represent electrical conductivity, or equivalently resistivity. In a variant, the CRP represents the concentration of a substance in the fluid, specifically a substance present in fresh dialysate, such as bicarbonate, or an electrolyte, such as sodium, potassium, calcium, magnesium, chloride, etc. If the dialysate is produced for use in PD, the substance may instead be an osmotic agent, such as glucose. In a further alternative, the CRP may represent the concentration of hydrogen ions, for example in the form of a pH value. As illustrated, the sensor 22 provides a measurement signal S5 indicative of the CRP.

[0039] As mentioned above, the first fluid F1 is water, which is the main component in the dialysis solution. To maintain a continuous production of the dialysis solution, the container 3a may need to be refilled. For this purpose, the system 1 comprises a water supply 17 configured to produce water of sufficient quality for use in the dialysis solution. The supply 17 is connected to the container 3a by a water supply line 18. The supply 17 is operable to receive a control signal C7 to supply water to the container 3a in order to fully or at least partially refill the container 3d during a refilling phase. As will be explained below, the refilling phase can be selectively initiated when the container 3a is considered to be (sufficiently) empty.

[0040] In FIG. 1, the bypass line 20a is arranged to extend from the first fluid line 4a to the drain path. The system 1 further includes a valve device operable in different states. In a first state, the fluid flow is directed along the first fluid line 4a to the dialyzer 7. In a second state, the fluid flow is prevented from flowing to the dialyzer 7 and is instead diverted to the bypass line 20a and directed from the bypass line 20a to the drain path towards the drain 16. Thus, in the second state, a "bypass path" is defined that includes the bypass line 20a and the line segments 20b, 20c. In a third state, EF can selectively flow along the drain path from the container 3d to the drain 16, i.e. through the drain line 14 and the line segments 20b, 20c. The valve device is not operable in the first and second states simultaneously (mutually exclusive), nor in the second and third states. Depending on the implementation, the valve device may or may not be operable in the first and third states simultaneously. In the illustrated example, the valve device comprises first and second valve devices 21a, 21b disposed at the upstream and downstream ends of the bypass line 20a, respectively. Each valve device 21a, 21b may be a three-way valve, or a combination of on / off valves, as illustrated. The state of the valve device is set by control signals C8, C9 for the first and second valve devices 21a, 21b. In cases where the fluid pathways in the system are defined by disposable devices (below), the valve device may comprise an actuator configured to engage the outside of a dedicated tube to selectively close the fluid passageway. Such a valve device may comprise any type of pinch valve or clamp.

[0041] As shown in FIG. 1, the controller 30 is configured to control the operation of any of the systems described herein. If the system 1 is operated by a dialysis machine, the controller 30 may be a controller of the dialysis machine or a separate controller. The controller 30 is configured to receive measurement signals represented as Sj and to output control signals represented as Ci. As will be understood, Ci can include C1-C9 and Sj can include S1-S5. The controller 30 may be configured to generate the control signals Ci according to a control program including computer instructions. The control program is also configured to operate based on the measurement signals Sj. The controller 30 comprises a circuit including one or more processors 31 and a computer memory 32. The control program is stored in the memory 32 and executed by the processor 31. The control program may be provided to the controller 30 on a computer readable medium, which may be a tangible (non-transitory) product (e.g., magnetic media, optical disk, read-only memory, flash memory, etc.) or a propagating signal. In the illustrated example, the controller 30 provides the control signals Ci and comprises a signal interface 33a for receiving the measurement signals Sj. The control device 30 also includes an input interface 33b for connecting to one or more input devices 34 that allow an operator to input control data, and an output interface 33c for connecting to one or more UI devices 35 for providing feedback data to the operator. For example, the input devices 34 may include a keyboard, a keypad, a computer mouse, control buttons, a touch screen, a printer, a microphone, etc., and the UI devices 35 may include a display device, a touch screen, an indicator lamp, an alarm device, a speaker, etc. The operator may be a person with clinical experience, such as a doctor or nurse, or a patient.

[0042] The system 1 of FIG. 1 also includes a number of connectors 19a-19f attached to various fluid lines. The provision of connectors 19a-19f allows the system 1 to include disposable parts or "disposable devices" that can be connected to corresponding connectors in the system and are discarded after use. The disposable parts engage with the mechanical parts to form at least a part of the system. In a dialysis system, the mechanical parts are generally referred to as dialysis devices or "monitors." The disposable parts may vary depending on the modality of treatment being performed. An example of a disposable part 1a for HD treatment is shown in FIG. 2A. The disposable part 1a may be a single component, as shown, or may be a collection of connectable sub-parts. The disposable part 1a is provided as a dedicated accessory for attachment to the mechanical parts. Although not shown in FIG. 2A, the disposable part 1a may also include one or more of the containers 3b, 3c that are filled with liquid concentrate when delivered. As is known in the art, the dialyzer 7 and blood lines 8a, 8b are also disposable and may or may not be included in the disposable part 1a.

[0043] In FIG. 2A, disposable part 1a defines a fluid pathway on the "non-blood side" of the system. Specifically, disposable part 1a includes water supply line 18, container 3a, fluid lines 4a, 4b, 4c, junctions 6', 6'', bypass line 20a, outflow line 12, container 3d, drain line 14, and line segment 20b. Connector 19a is disposed at the end of line 18 for connection to supply device 17, connector 19b is disposed at the end of line 4b for connection to container 3b, connector 19c is disposed at the end of line 4c for connection to container 3c, connector 19d is disposed at the end of line 4a for connection to the inlet to the second chamber of dialysis machine 7, connector 19e is disposed at the end of outflow line 12 for connection to the outlet of the second chamber of dialysis machine 7, and connector 19f is disposed at the end of line segment 20b for connection to CRP sensor 22. The provision of connectors 19b, 19c allows the operator to remove the containers 3b, 3c when empty and reattach new containers 3b, 3c filled with concentrates F2, F3. The disposable part 1a is discarded after use, for example after completion of a treatment period, after a predefined maximum use time, or whenever a new patient is treated.

[0044] In the disposable part 1a, the fluid lines may be defined by plastic tubing. As mentioned above, the pumps P1-P6 may be peristaltic pumps that engage the outside of the tubing to generate a moving compression of the tubing and move the fluid along the tubing. Conventionally, to enable the use of peristaltic pumps, the tubing is provided with dedicated engagement portions, also known as pump segments, that are configured to be engaged by the compression elements of the peristaltic pump. In FIG. 2A, pump segments 5a', 5b', 5c' are configured to be engaged by pumps P1, P2, P3 (FIG. 1), and pump segments 13', 15' are configured to be engaged by pumps P4, P6 (FIG. 1).

[0045] The disposable part 1a may be engaged with a mechanical part 1b shown in FIG. 2B. In the illustrated example, the mechanical part 1b comprises pumps P1-P6 accessible for engagement with pump segments of the disposable part 1a. The mechanical part 1b also comprises valve arrangements 21a, 21b accessible for engagement with fluid lines in the disposable part 1a. Scales 2a-2d are also included in the mechanical part 1b and configured to carry respective containers 3a-3d. The mechanical part 1b also comprises a control device 30, thereby constituting an operating device for performing the RRT. In the example of FIG. 2B, the mechanical part 1b also includes a CRP sensor 22, although alternative arrangements are possible (below).

[0046] FIG. 3A shows the system 1 as it is operated by the control device 30 (FIG. 1) to perform HD therapy. In FIG. 3A and all other figures, the open / fill pump symbol represents a pump that is stopped / operating, and the open / fill valve symbol represents a valve path that is closed / open. In FIG. 3A, the pumps P1-P3 are jointly operated to pump water (F1) and concentrate (F2, F3) in a well-defined ratio into the supply line 4a, while the valve device is set to a first state to direct the fluids F1-F3 into the first chamber of the dialyzer 7. In this process, the water and concentrate are mixed with the dialysate in the line 4a. At the same time, the pump P5 is actuated to pump blood through the second chamber of the dialyzer 7. The pump P4 is also operated to pump the effluent from the dialyzer 7 into the container 3d. By appropriate operation of the pumps P1-P4, fluids can be extracted from the blood in the dialyzer 7 through the membrane 7'. This extraction of fluid is known as ultrafiltration, and the extracted fluid is called ultrafiltrate. The rate of ultrafiltration at any given time is given by the difference in flow rates between pumps P4 and P1, i.e., the outflow of effluent from dialyzer 7 and the inflow of dialysate to dialyzer 7. Both the rate of ultrafiltration (UFR) and the accumulation of ultrafiltrate (UF) can be monitored by use of signals S1-S4. UFR is equal to the difference between the weight gain per unit time of container 3d and the sum of the weight losses per unit time of containers 3a-3c. UF over a period of time is given by the difference between the weight gain of container 3d and the sum of the weight losses of containers 3a-3c over that period of time. In some embodiments, controller 30 is configured to control pumps P1 and / or P4 based on output signals S1, S4 to achieve setpoints for UFR and / or UF.

[0047] It is understood that the system 1 is operated to produce dialysate on-line and on-demand, and the dialysate is produced within the disposable part 1a. This means that an existing dialysis machine equipped with a scale can be configured for on-line production of dialysate by fitting a suitably configured disposable part 1a and by reconfiguring the control device (30 in FIG. 1), for example by updating its control program.

[0048] During the dialysis treatment, the fluid levels in the containers 3a, 3b, and 3c decrease and the fluid level in the container 3d increases as indicated by the arrows. Eventually, the container 3a will be depleted of water and it will be necessary to refill the container 3a by initiating the refill phase described above. Similarly, the container 3d will eventually be filled with effluent (EF) and it will be necessary to drain the container 3d by initiating the drain phase described above. The controller 30 can monitor the need for refilling and draining based on the weights of the respective containers 3a, 3d, given by signals S1, S4. FIG. 3B shows the system 1 during the refilling and draining phases, which are performed simultaneously in this example. In the refilling phase, the supply device 17 is activated to supply water and increase the fluid level in the container 3a. In the draining phase, the pump P6 is activated to pump EF from the container 3d to the drain path and the valve device is set to its third state to direct the EF to the drain 16. In the illustrated example, the dialysis treatment is interrupted during the draining and refilling phases by stopping the pumps P1-P5. However, pump P5 may be operating to avoid clogging of the blood lines. In an alternative embodiment, which is a superposition of Figures 3A and 3B, dialysis therapy continues during the drain and / or refill phases. It will be appreciated that UFR and UF cannot be reliably monitored or controlled by using signals S1-S4 during such drain and refill phases.

[0049] The liquid concentrates F2, F3 are consumed at a much lower rate than the water F1. When the control device 30 detects, based on the signals S2, S3, that one of the containers 3b, 3c has become empty, a warning is generated on the UI device 35 (FIG. 1) and the operator can be prompted to replace the container. During the replacement, the dialysis treatment is stopped and the operator manually disconnects the connectors 19b / 19c from the empty container 3b / 3c and attaches the full container 3b / 3c. The control device 30 is then operated to resume the dialysis treatment.

[0050] FIG. 4 is a flow chart of an exemplary method 400 of controlling fluid flow in the system 1. The method 400 may be performed by the controller 30. The method 400 includes two preparatory steps PH1, PH2, which are performed before the dialysis treatment and are intended to derive the above-mentioned "mixed control data" (MCD) by use of the CRP sensor 22. The MCD is then used by the controller 30 to control the pumps P1-P3 to generate dialysate during the dialysis treatment. In FIG. 4, optional steps are indicated by dashed lines. Some of these optional steps are performed in the system of FIG. 1, but may be omitted in alternative systems, as will be further described below.

[0051] When PH1 is performed in the system of FIG. 1, the valve device is set to its second state (step 401), as shown in FIG. 5A. This closes the first fluid line 4a ("supply path"), opens the bypass path, and opens a passage from the supply path to the bypass path. As seen in FIG. 5A, fluid is directed from line 4a through lines 20a, 20b to drain 16 while passing through CRP sensor 22. PH1 includes steps 402-406. In step 402, pump P1 is operated to convey water (fluid F1) from first container 3a to lines 4a and 20a, 20b. In FIG. 5A, pumps P2, P3 are presumed to be blocked, thereby essentially blocking lines 4b, 4c when not activated. If desired, controllable on / off valves (not shown) can be placed along fluid lines 4b, 4c to selectively block fluid flow. In step 403, pump P2 is operated to convey A concentrate (fluid F2) from the second container 3b to line 4a and lines 20a, 20b. Pump P2 may be started simultaneously with pump P1 or after. FIG. 5A shows system 1 when both pumps P1, P2 are operating during PH1. At this time, a mixture of F1 and F2 passes through CRP sensor 22. In step 404, signal S5 from CRP sensor 22 is evaluated for determination of a current CRP value, which is compared with a first target CRP value TV1, which defines the required characteristics of the mixture of F1 and F2 to be included in the generated dialysis fluid. TV1 may be predefined and stored in the internal memory 32 of control device 30 or may be input by an operator via input device 34 (see FIG. 1). Alternatively, a selected mixing ratio between F1 and F2 may be input by an operator and converted to TV1 by control device 30. If the current CRP value is found to deviate from TV1, the speed of pump P1 and / or pump P2 is adjusted in step 405. Steps 404-405 are repeated until the current CRP value matches TV1. Steps 404-405 thus define an adjustment procedure.In some embodiments, it may be desirable for the flow of fluid in the supply path to be fixed during PH1. In the system shown in FIG. 5A, this can be easily achieved by simply adjusting pump P2 in step 405. If the current CRP value matches TV1, then in step 406, a first weight change relationship WCR1 is determined by using signals S1, S2. WCR1 is part of the MCD and defines the relationship (W1:W2) between the weight change per unit time of container 3a (W1) and the weight change per unit time of container 3a (W2). The weight change per unit time may be determined by running any conventional differentiation algorithm on the respective signals S1, S2.

[0052] Then, the method 400 proceeds to execute PH2, which includes steps 407 to 411. In step 407, the pumps P1, P2 are operated to fill WCR1 according to the signals S1, S2, and then the speeds of the pumps P1, P2 are fixed. In step 408, the pump P3 is operated to convey the B concentrate (fluid F3) from the third container 3c to the line 4a and the lines 20a, 20b. FIG. 5B shows the system 1 when the pumps P1, P2, P3 are operated during PH2. At this time, a mixture of F1, F2, F3 passes through the CRP sensor 22. In step 409, the signal S5 from the CRP sensor 22 is evaluated for the determination of a current CRP value, which is compared with a second target CRP value TV2 that defines the required characteristics of the dialysis fluid to be produced. TV2 can be obtained in the same way as TV1. If the current CRP value is found to deviate from TV2, the speed of the pump P3 is adjusted in step 410. Steps 409-410 define the adjustment procedure corresponding to steps 404-405. Thus, steps 409-410 are repeated until the current CRP value matches TV2. If the current CRP value matches TV2, then in step 411, a second weight change relationship WCR2 is determined by using signals S1, S2, S3. WCR2 is part of the MCD and defines the relationship between the weight change per unit time (W3) for container 3c and the weight change per unit time for container 3a and / or container 3b depending on the definition of TV2. Thus, the relationship can be given as W3:W1, W3:W2, or W3:(W1+W2).

[0053] After completion of PH2, set points for the dialysis treatment to be performed are obtained according to conventional practice (step 412). The set points may define, for example, the flow rate of fresh dialysate to the dialyzer 7 ("main flow"), the UFR, the UF, the blood flow rate through the dialyzer 7, etc. The set points may be retrieved from the internal memory 32 or may be entered by the operator via the input device 34 (see FIG. 1).

[0054] In step 413, the system 1 is operated according to the setpoint to produce dialysate. Step 413 may be performed immediately after PH2 or at a later time. In step 413, the pumps P1, P2, P3 are controlled based on the signals S1, S2, S3 to achieve WCR1 and WCR2. In other words, the pumps P1, P2, P3 operate at speeds that result in weight changes in the containers 3a, 3b, 3c that fill WCR1 and WCR2. Once WCR1 and WCR2 are filled, dialysate has been produced. Step 413 may also include controlling the pump P1 to deliver dialysate at a target flow rate given by the setpoint.

[0055] While step 413 is performed to generate dialysate, the valve device is set to its first state (step 414). This opens line 4a ("supply path") and closes the passage from line 4a to the bypass path. In step 415, pump P4 may be operated based on signal S4 related to signals S1-S3 to achieve UFR according to a set value. Although not shown in FIG. 4, pump P5 operates to generate a blood flow rate according to a set value. System 1 is thereby operated to perform dialysis therapy, as shown in FIG. 3A.

[0056] Note that system 1 is, by definition, considered to produce dialysate whenever it is operated according to the blending control data MCD. In the example of FIG. 4, dialysate is produced by blending three fluids, and MCD includes WCR1 and WCR2. Thus, in this example, dialysate is produced by system 1 whenever system 1 operates to achieve WCR1 and WCR2. At all other times, the system is considered to produce a "blend" of fluids, for example, during the adjustment procedures of PH1 and PH2.

[0057] In some embodiments, the main flow rate is changed during the dialysis treatment, for example according to a schedule contained in the setpoints or by operator intervention via the input device 34 (FIG. 1) during an ongoing treatment. This can be achieved by changing the pumping speeds of the pumps P1, P2, P3 together based on the signals S1-S3 such that WCR1 and WCR2 are met. In some embodiments, while the pumps P1-P3 are being adjusted, the valve device can be intermittently set to its second state to open the bypass path when the main flow rate should be changed, in order to avoid a mixture of F1, F2, F3 not meeting the dialysate specifications being delivered to the dialyzer 7.

[0058] As shown in FIG. 4, the method 400 may include a verification step 416, in which a bypass path is intermittently opened to carry dialysate through the CRP sensor 22 during the ongoing dialysis treatment while the pumps P1, P2, P3 are operating, thereby essentially pausing the dialysis treatment. In step 416, the CRP value is determined based on the signal S5 and compared to TV2. If the CRP value matches TV2, the bypass path is closed, thereby resuming the dialysis treatment. If a sufficient deviation is detected, the method 400 may begin running PH1 and PH2 to determine updated WCR1, WCR2. Alternatively, the method 400 may terminate the dialysis treatment and / or generate a warning to the operator on the UI device (35 in FIG. 1).

[0059] The verification step 416 may be performed at regular intervals during treatment, when the set points are changed during an ongoing treatment, or whenever a new container 3b, 3c of liquid concentrate is installed. When a new container 3b, 3c is installed, the method 400 may proceed directly to performing PH1 and PH2 without performing the verification step 416.

[0060] Alternatively or additionally, verification step 416 may be performed whenever the speed of any one of pumps P1-P3 is found to deviate from an operating speed range, which may be defined as a range of allowable speed values ​​for the respective pump or, for example, as an allowable change in the speed of each pump relative to the initial speed of each pump when step 413 is initiated, i.e. when dialysate is first produced at the target flow rate.

[0061] Whenever the bypass pathway is opened during an ongoing treatment, the controller 30 may be configured to estimate, based on the signals S1-S3, the amount of dialysate that will be delivered to the bypass pathway instead of being delivered to the dialyzer 7. The estimate may be given as the sum of the integrated weight decreases in the signals S1-S3 during the period that the bypass pathway is open. This estimate may be subtracted when the controller 30 calculates the cumulative amount of ultrafiltrate (UF) for the dialysis treatment.

[0062] As shown in FIG. 4, the method 400 may include a protection step 417 in which the speeds of the pumps P1-P3 are evaluated with respect to a set of speed limits for error detection. An error in the system 1, e.g., a kink in the fluid line or a mechanical failure of the pump, may cause the speed of the pump to change significantly. The set of speed limits defines a maximum and / or minimum speed limit for each pump. If the current speed of a pump is found to be below its minimum speed limit or above its maximum speed limit, step 417 may cause the system 1 to shut down and / or generate an alarm via the UI device 35.

[0063] Alternative implementations of PH2 are possible. For example, in step 407, only one of pumps P1 and P2 may be active. This means that steps 407-408 result in a mixture of F1 and F3, or F2 and F3, which is conveyed through the CRP sensor 22 during the adjustment procedure of steps 409-410. The resulting WCR2 defines the relationship W1:W3 or W2:W3.

[0064] The order in which the fluids F1-F3 are mixed into PH1 and PH2 can be selected taking into account the required or available measurement range (calibration range) of the CRP sensor 22. The measurement range indicates the range of CRP values ​​that are measured with sufficient accuracy by the sensor 22. An inexpensive CRP sensor 22 can have a very narrow available measurement range. To minimize the required measurement range, the order of the fluids can be selected to minimize the difference between TV1 and TV2. For example, if the conductivity is measured by the CRP sensor 22, the smallest measurement range is obtained if PH1 is performed on a mixture of water and concentrate A (F1, F2) and PH2 is performed on a mixture of water, concentrate A and concentrate B (F1, F2, F3), i.e., as shown in FIG. 4.

[0065] As indicated by the dashed arrows in Fig. 4, the method 400 may return to the preparation stages PH1, PH2 at any time, thereby making a new determination of the MCD. As mentioned above, such a new determination may be triggered by the verification step 416. In another example, the method 400 may return to PH1 and PH2 if the composition of the medical fluid is changed, for example, based on user input or according to a predefined schedule. The change in composition is provided by a change in TV1 and / or TV2 (see steps 404, 409).

[0066] 6-7 show alternative installations of a CRP sensor 22 in a bypass path in a system for dialysis treatment. The system of FIG. 6 differs from the system of FIG. 1 in that the bypass path is defined by a bypass line 20 extending from line 4a to drain 16. Note that the CRP sensor 22 is disposed in the bypass line 20, and the valve device 21b is omitted since it is non-functional here. As shown, the CRP sensor 22 may be removably connected to a connector 19f included in the disposable part (see FIG. 2A). The system of FIG. 7 differs from the system of FIG. 1 in that the CRP sensor 22 is disposed in the bypass line 20a. As shown, the CRP sensor 22 may be removably connected to connectors 19f, 19g included in the disposable part. One technical advantage of the system of FIG. 6-7 over the system of FIG. 1 is that the CRP sensor 22 is not exposed to effluent. This may further extend the operational life of the CRP sensor 22 and / or reduce the need for rinsing, disinfection, or other maintenance. On the other hand, when the CRP sensor 22 is exposed to the effluent, during a dedicated operating sequence for the system, the signal S5 can be processed to assess the effectiveness of the dialysis therapy, for example according to US Pat. No. 5,024,756 or US Pat. No. 6,217,539.

[0067] In the systems illustrated herein, it may be desirable to ensure thorough mixing of the fluids in the supply path (line 4a) upstream of its connection to the bypass path, thereby ensuring that the fluid mixture reaching the CRP sensor 22 is uniform regardless of how far downstream of the bypass path the CRP sensor 22 is located.

[0068] As mentioned above, the controller 30 may be configured to control the speed of the pumps P1-P3 based on the signals S1-S3 from the scales 2a-2c. To this end, the controller 30 may implement any conventional feedback control, including but not limited to P, PI, or PID control. In cases where the time constants of the scales 2a-2c are large, slowing down the scale response to weight changes, dynamic performance may be improved by so-called cascade control, well known to those skilled in the art.

[0069] It should be understood that the dialysate may be produced by mixing any number of fluids. Thus, the system shown herein may include one or more additional containers of liquid concentrates arranged on respective scales, and the method of FIG. 4 may be extended with one or more additional preparation steps for determining the weight change ratio. Similarly, the dialysate may be produced by mixing only two fluids, which means that PH2 is omitted in method 400, and step 413 is modified to operate only pumps P1 and P2 to achieve WCR1 given by PH1.

[0070] It should also be noted that the amount of effluent conveyed from the dialyzer 7 does not need to be monitored by use of the scale 2d. Instead, a flow meter or volumetric pumping can be used to monitor the amount of effluent. Thus, instead of collecting the effluent in the container 3d, the effluent may be directed directly to a drain 16 or to a reservoir where the weight is not monitored.

[0071] In a further variation of the system 1 of FIG. 1, the bypass path is omitted, and therefore steps 401, 414, and 417 of the method of FIG. 4 are also omitted. Instead of being sent to the bypass path during PH1 and PH2, the mixture can be sent along the supply path (line 4a) to and through the dialyzer 7 if it is considered not harmful to the patient. After passing through the dialyzer 7, the mixture may be collected in a container 3d or diverted to a dedicated drain line extending from the drain line 12 to the drain line 16. In such a variation, the CRP sensor 22 is placed in the outflow line 12 or in the dedicated line. In another variation, the line 4a is disconnected from the dialyzer 7 during PH1 and PH2 and instead connected to the CRP sensor 22. In the example of FIG. 1, the connector 19d is temporarily released from the dialyzer 7 and attached to the CRP sensor 22 instead of the connector 19f.

[0072] The method of FIG. 4 is not limited to HD, but may be applied to any system for RRT, including any modality of extracorporeal blood therapy and PD. FIG. 12 shows a system 1' for generating medical fluid for any type of RRT. The system 1' does not need to be part of or connected to a system for dialysis treatment. The illustrated system 1' is configured to generate medical fluid by mixing two fluids F1, F2, but may be extended to mix additional fluids as needed. The components of FIG. 1 and FIG. 12 are identical insofar as they are given the same reference numbers. The description of such components will not be repeated. In FIG. 12, the outlet of the first fluid line 4a (supply path) includes a connector 19d coupled to a connector 40a of the receiving device 40. The system also includes a control device (not shown) configured to perform at least PH1 and step 413 of the method 400 of FIG. 4. Since the system of FIG. 12 includes a bypass path represented by the bypass line 20, the control device can also perform steps 401 and 414, as well as the verification step 416. The receiving device 40 is configured to receive the medical fluid generated by the execution of step 413. In some embodiments, the medical fluid is a dialysate for use in extracorporeal blood therapy such as HD or HDF, and the receiving device 40 comprises a dialyzer 7 (FIG. 1). In some embodiments, the medical fluid is a replacement fluid for use in HF or HDF, and the receiving device 40 comprises an injection port on the withdrawal line 8a and / or on the return line 8b (FIG. 1). In some embodiments, the medical fluid is a dialysate for use in PD, and the receiving device 40 comprises a disposable fluid circuit attached to a PD cycler. It is also conceivable that the receiving device 40 corresponds to the peritoneal cavity itself. In some embodiments that are applicable to all types of RRT, the receiving device 40 is a reservoir for collecting medical fluid for subsequent use in RRT. In such embodiments, the medical fluid is not generated on demand. The reservoir may be connected to a system for dialysis treatment or may not be part of the system.

[0073] In some embodiments, the system 1' is included in a separate fluid generating device configured to supply medical fluid to the dialysis machine.

[0074] System 1' of Figure 12 may be comprised of disposable and mechanical components, similar to system 1 of Figure 1. Although clear technical advantages are achieved by limiting the production of medical fluids to disposable components, systems 1, 1' may also be implemented to produce medical fluids within permanent structures.

[0075] In some embodiments, some or all of the fluid lines in the disposables are configured as passages within a single cassette. The pump and / or valve system may or may not be integrated into the cassette. If integrated, the pump may be implemented as a membrane pump, for example.

[0076] In a further alternative, the containers 3b, 3c may be refillable by being fluidly connected to respective sources of liquid concentrate.

[0077] In the system 1, 1' shown in the figures, the pump P1 is arranged in or on the first fluid line 4a downstream of the junction 6' (and junction 6'', if present). Thereby, the first pump P1 not only draws the fluid F1 from the container 3a, but also defines the flow rate of the medical fluid ("main flow rate"). This provides the technical advantage of simplifying the regulation of the main flow rate. However, in some embodiments, the pump P1 may instead be arranged upstream of the junction 6'.

[0078] In some embodiments, not shown, the system 1, 1' further comprises one or more sterilizing grade filters, e.g., in the first fluid line 4a, downstream of junction 6' (and / or junction 6'', if present). It may be preferable to place the filter near the medical fluid outlet, e.g., between the valve device 21a and the connector 19d. The filter may be configured to ensure that the medical fluid meets the standards for ultra-pure dialysate or replacement fluid in terms of viability (sterility) and endotoxins. Such filters are well known in the art.

[0079] For the reasons discussed above, the CRP sensor 22 can have a long operational life. In particular, the operational life of the CRP sensor 22 can exceed the operational life of the disposable part 1a (FIG. 2A). Thus, the CRP sensor 22 can be considered to be "reusable." To enable reuse, the disposable part is configured to be removably attached to the CRP sensor 22. In the illustrated example, the disposable part includes one or more terminal connectors for establishing a releasable fluid connection to the CRP sensor 22 (see 19f in FIGS. 1, 6, 7, and 12, and 19g in FIG. 7).

[0080] In some embodiments, the system includes an auxiliary CRP sensor in addition to the reusable CRP sensor 22. In some embodiments, the auxiliary CRP sensor is a disposable component. In FIG. 12, the disposable CRP sensor 122 is disposed in line 4a upstream of the valve device 21a. The disposable sensor 122 may be a component of the disposable component, which may be configured to define a fluid path of the system, similar to the disposable component 1a described with reference to FIG. 2A. The disposable sensor 122 may be disposed of together with the disposable component. The disposable sensor 122 is a low-end sensor device. Although relatively inexpensive, such sensor devices generally perform poorly in terms of precision and / or accuracy and are therefore not suitable for use in determining the MCD. The purpose of the disposable sensor 122 is instead to detect changes in the composition of the medical fluid while it is being produced by step 413. Such changes may be harmful to the patient and may be caused by errors in the concentrate or water supply, for example, by an operator manipulating the contents of the concentrate container. The controller may therefore be configured to perform safety procedures while the medical fluid is being produced. The safety procedure assumes that the signal drift of the disposable sensor 122 is small during its deployment. An exemplary safety procedure 1300 is shown in FIG. 13A. In the safety procedure, CRP values ​​are obtained from the disposable sensor 122 (step 1301) and evaluated for detection of deviations indicative of a change in composition (step 1302). Upon detection of such deviations (step 1303), the controller takes a dedicated action (step 1304). The dedicated action may include, for example, performing the verification step 416, shutting down the system 1', generating an alarm, etc., depending on the magnitude of the deviation. To improve the performance of the disposable sensor 122, the controller may also perform a calibration procedure, for example, while the medical fluid is being produced according to step 413. An exemplary calibration procedure 1310 is shown in FIG. 13B. In the calibration procedure 1310, the controller opens the bypass path (step 1311) if it is not already open.The controller then obtains (1312) a first set of CRP values ​​from the signal S5 of the sensor 22 and a second set of CRP values ​​from the signal S5' of the disposable sensor 122 (step 1313). Steps 1312-1313 assume that the first and second sets of CRP values ​​represent the same fluid, e.g., a medical fluid or any intermediate mixture (see below). The first and second sets of CRP values ​​may be, but do not necessarily have to be, obtained simultaneously. The controller processes the first and second sets of CRP values ​​to determine a calibration factor for the disposable sensor 122 under the assumption that the first set of CRP values ​​is correct (step 1314). The calibration factor is given by one or more parameter values ​​of a conversion function that converts the CRP values ​​measured by the disposable sensor 122 to the corresponding CRP values ​​measured by the sensor 22. For example, the calibration factor may include an offset value (positive or negative) that is added to the CRP values ​​from the disposable sensor 122. The controller completes the calibration procedure 1310 by storing the calibration coefficients in memory, closing the bypass path, and beginning to transmit medical fluid to the receiving device 40 .

[0081] Steps 1312-1313 may be performed at least partially during the adjustment procedure. In the example of FIG. 4, the first set of CRP values ​​may comprise one or more CRP values ​​measured at or after the end of the preparation phase PH2, i.e. when the current CRP value corresponds to the target value TV2 (see step 409). In the example of FIG. 4, step 1312 may also be performed at or after the end of the preparation phase PH1, when the current CRP value corresponds to the target value TV1 (see step 404). Thus, if the medical fluid is produced by mixing two or more constituent fluids, steps 1312-1313 may be performed not only to obtain the CRP value of the medical fluid, but also to obtain the CRP values ​​of one or more intermediate mixtures produced during the adjustment procedure. The use of intermediate mixtures expands the range of CRP values ​​in the first and second sets. The accuracy of the calibration coefficient may be improved by considering a wider range of CRP values ​​around the target value of the medical fluid. For example, in step 1314, the relationship between the first and second CRP values ​​within the range may be fitted, for example, by linear least squares, to a line representing the agreement between the first and second CRP values. In this fitting, the CRP values ​​may or may not be weighted, for example, to relatively increase the influence of the CRP values ​​measured for the medical fluid compared to the CRP values ​​measured for the intermediate mixture. The fitting results in the conversion function described above, and therefore also in the calibration factor. Furthermore, since the conversion function is determined for a range of CRP values, the conversion function also defines the calibration factor to be applied in the safety procedure 1300 when the target value (TV2) of the medical fluid is changed within the range that occurs when the composition of the medical fluid is changed.

[0082] As shown by step 1302A in Fig. 13A, the controller may be configured to retrieve and apply a calibration factor during a safety procedure to correct the CRP value from the disposable sensor 122 before evaluating the thus corrected CRP value for deviation detection. The calibration procedure 1310 is facilitated by placing the disposable sensor 122 in the main supply path so as to be exposed to the medical fluid, and upstream of a diversion from the main fluid path to a bypass path (control valve 21a) so as to simultaneously expose the sensors 22, 122 to the medical fluid. However, it is contemplated that the disposable sensor 122 is instead placed downstream of the control valve 21a, and the controller obtains (at step 1312) a first set of CRP values ​​while the bypass path is open and a second set of CRP values ​​while the bypass path is closed.

[0083] FIG. 8 is a flow chart of an exemplary method 800 of configuring and operating a system to generate a medical fluid. Method 800 may be performed by a controller in any of the systems described herein. In step 801, a user (operator) attaches a disposable component to a machine component and properly engages a scale, pump, etc. The machine component may be a dialysis machine or any other machine with the necessary pump, scale, etc. In step 802, the user connects the disposable component to the reusable CRP sensor 22 so that the reusable CRP sensor 22 is included in the bypass path. Method 400 of FIG. 4 is then performed to generate a medical fluid. At some point, method 400 ends and step 803 is performed to initiate a procedure to ensure the reuse of the CRP sensor 22. An example of step 803 is described below. Once step 803 is completed, step 804 is performed to have the user remove the disposable component from the machine component and discard the disposable component. It is contemplated that a subset of the disposable components are reusable and are left on the machine component in step 804. For example, if containers 3b, 3c are included in the disposable portion, containers 3b, 3c may be left on scales 2b, 2c. Steps 801-804 may include providing user instructions on UI device 35 (FIG. 1) to cause a user to perform one or more actions. Thus, in the context of this disclosure, causing a user to perform an action is equivalent to outputting instructions to cause a user to perform an action.

[0084] Step 803 may vary depending on the location and integration of the CRP sensor 22 within the system.

[0085] In some embodiments, the CRP sensor 22 is integrated into a water supply 17. An example of such a supply 17 is shown in FIG. 9. The operation of the supply 17 is controlled by an internal controller (not shown). The device 17 includes a water treatment device 90 operable to treat influent water to produce purified water for use in medical fluids. The water treatment device 90 may be configured to purify the influent water by any available technique, such as a sediment filter, a carbon filter, a resin bed, ultrafiltration (UF), reverse osmosis (RO), nanofiltration, electrodeionization (EDI), or capacitive deionization (CDI). The device 17 includes a water supply line 91 extending from an inlet connector 91a to an outlet connector 91b. In operation, a tap water source can be connected to the inlet connector 91a, and a terminal connector 19a of the disposable (FIGS. 1 and 12) can be connected to the outlet connector 91b. The device 17 further includes an auxiliary fluid line 92 extending from the inlet connector 92a to the outlet connector 92b via the sensor 22. In operation, the terminal connector 19f of the disposable (FIGS. 1, 6, 7, and 12) may be connected to the inlet connector 92a, and a fluid line (not shown) extending to the drain 16 may be connected to the outlet connector 92b. The device 17 further comprises a cleaning unit 93 operable to perform a cleaning operation on the sensor 22 and, optionally, the water treatment device 90. The cleaning operation may include rinsing and / or disinfection. As used herein, rinsing involves flushing the CRP sensor with a fluid to remove deposits, particles, and the like. The fluid may be any liquid, including water, and may or may not include a cleaning agent, such as a detergent, descaling agent, and the like. As used herein, disinfection refers to a process that prevents the growth of microorganisms on the CRP sensor, and may involve heat treatment, flushing with a disinfectant or sterilant, and the like. It should be understood that not only the CRP sensor 22 is treated in the cleaning operation, but also the connecting fluid path. The device 17 further comprises an I / O unit 94 operable to output a signal S5 and, optionally, to receive a control signal. During operation, the I / O unit 94 is wired or wirelessly connected to the controller 30. In one embodiment of step 803, the controller 30 sends a control signal to the delivery device 17 to initiate a cleaning operation.In another implementation of step 803, the controller 30 prompts the user to initiate the cleaning operation via the UI device 35 (FIG. 1), for example by pressing a dedicated button (not shown) on the device 17.

[0086] Since the CRP sensor 22 is located in the bypass path, microbial growth in the CRP sensor 22 is less of a risk factor compared to when the CRP sensor 12 is located in the main supply path (line 4a). This reduces or even eliminates the need for disinfection. Nevertheless, since the CRP sensor 22 is reused for multiple periods, periodic cleaning may be performed over time to ensure proper functioning of the CRP sensor 22 over time. For example, rinsing may be performed to mitigate contamination, e.g., by scaling, deposits, etc. Cleaning to prevent microbial growth in the CRP sensor 22 may be relevant whenever there is a risk of microorganisms migrating along the bypass path into the main supply path. This risk may depend, for example, on the distance from the CRP sensor 22 to the main supply path and / or whether the bypass path is intermittently opened while the medical fluid is being produced (see verification step 416). It is understood that the cleaning operation may include rinsing and / or disinfection, and that rinsing and disinfection may be performed at different intervals. Additionally, unlike method 800 of FIG. 8, it is contemplated that the cleaning operation may be performed less frequently than after every period.

[0087] In some embodiments, the CRP sensor 22 is integrated into the machine part 1b (see FIG. 2B). If the machine part is equipped with an integrated cleaning unit for cleaning the sensor 22, the control device 30 can autonomously initiate the cleaning operation in step 803.

[0088] In some embodiments, the CRP sensor 22 is included in a separate device (not shown) that may or may not be attached to the machine part 1 b or the feeding device 17 .

[0089] 10A-10B show an example of a CRP sensor 22, which is arranged inside a device 100, which may be a machine part 1b, a supply device 17, or a separate device as mentioned above. Here, it is assumed that the device 100 lacks functionality for rinsing or disinfecting the sensor 22. The sensor 22 defines an internal channel 22' and is configured to measure the CRP value of a fluid in the channel 22'. The device 100 defines an inlet port 23a and an outlet port 23b in fluid communication with the channel 22' on the flow path 23. Although not shown, the device 100 comprises an I / O unit for transferring measurement data (see signal S5) to the control device 30. FIG. 10A shows a first connection state achieved in step 802 of FIG. 8. In the first connection state, the sensor 22 is arranged in a bypass path. In the illustrated example, the bypass path comprises first and second interconnectable line segments 20b1, 20b2, which jointly correspond to line 20b in FIG. 1, line 20 in FIG. 6 or FIG. 12, or line 20a in FIG. 7. In particular, line segment 20b2 comprises terminal connector 19f configured to connect to inlet port 23a and terminal connector 20c2 configured to connect to terminal connector 20c1 on line 20b1. Furthermore, line segment 20c is connected to outlet port 23b by terminal connector 20c3 and extends to drain 16. FIG. 10B illustrates a second connection state achieved in step 803 of FIG. 8. In the second connection state, sensor 22 is enclosed in a closed loop and filled with a dedicated fluid configured to extend the operational life of sensor 22. For example, the dedicated fluid may be a bacteriostatic fluid. The bacteriostatic liquid includes a bacteriostatic agent (also known as a germicide), which is a biological or chemical agent that stops the growth of bacteria or kills bacteria. Thus, in the second connected state, the sensor 22 is maintained in an environment that prevents the growth of bacteria. To achieve the second connected state, step 803 may include operating the system 1, 1' to convey a dedicated fluid from the source into a bypass path and through the sensor 22. When the sensor channel 22' includes a dedicated fluid that can be detected from the signal S5, step 803 includes instructing the user to disconnect the line 20b1 from the line 20b2, disconnect the line 20c from the port 23b, and attach the terminal connector 20c2 to the port 23b.This operation retains the proprietary fluid within sensor 22. The operations of Figures 10A-10B include reusing components of the disposable to fluidly connect ports 23a, 23b. If method 800 is performed at a later time while device 100 is in the second connected state, step 802 may include instructing a user to disconnect and discard line segment 20b2 before connecting a new disposable to device 100 according to the first connected state (Figure 10A).

[0090] The dedicated fluid may be separate from the fluids F1, F2, F3 and may be delivered in the bypass path from a separate source by a dedicated pump. However, in some embodiments, the dedicated fluid includes at least one of the liquid concentrates included in the medical fluid. For example, the A concentrate has bacteriostatic properties and may be used as the dedicated fluid in step 803. With reference to FIG. 1, the valve devices 21a, 21b may be set to their second state, the pump P3 may be stopped, and the pumps P1, P2 may be operated at the same speed to deliver the A concentrate into the sensor 22. It will be appreciated that the ability to use one of the liquid concentrates as the dedicated fluid in step 803 greatly simplifies the construction of the systems 1, 1'.

[0091] 10A-10B show only one example of how the sensor 22 can be manipulated to retain the proprietary fluid within the sensor. For example, the ports 23a, 23b may be sealed in other ways to retain the proprietary fluid. Furthermore, the technique of retaining the proprietary fluid within the sensor 22 in step 803 is also applicable when the sensor 22 is integrated within the machine part 1b or the supply device 17.

[0092] FIG. 11 is a flow chart of an exemplary method 1100 that may be performed during the production of medical fluid in the systems 1, 1′. The method 1110 is described with reference to the system 1′ of FIG. 12. When an interruption in the operation of the receiving device 40 is detected (step 1101), the valve device 21a is operated to open the bypass path and direct the medical fluid to the drain 16 (step 1102). It is now assumed that the interruption prevents the device 40 from receiving medical fluid. The control device of the system 1′ can detect the interruption based on an output signal from the receiving device 40 or from a sensor, for example a pressure sensor (not shown) in the line 4a. In connection with step 1102, the speed of at least the pump P2 is reduced but not stopped (step 1103) to minimize the waste of the liquid concentrate F2. Thus, both pumps P1, P2 are still operable. When a resumed operation of the receiving device 40 is detected (step 1104), the speeds of the pumps P1, P2 are controlled to meet the target flow rate and achieve the WCR1 (step 1105). In conjunction with step 1104, the valve device 21a is operated to close the bypass path and direct the medical fluid to the receiving device 40 (step 1106). It is contemplated to implement step 1104 with a timeout function that will cause the system 1' to shut down if resumed operation is not detected within a predetermined time from step 1101.

[0093] By the method 1100, the pumps P1, P2 are maintained in operation during the interruption of the receiving device 40. If the pumps P1, P2 are stopped, hysteresis effects may require the controller to restart PH1 to update the WCR1. It is contemplated that in step 1103, both pumps P1, P2 are operated to reduce their speed. Furthermore, when operating at the reduced speed, the pumps P1, P2 may be controlled to maintain the WCR1 given by the signals S1, S2. Thereby, medical fluid is still produced in step 1103, albeit at a reduced flow rate. This allows the controller to verify from the signal S5 that the CRP value meets TV1 throughout the interruption, further reducing the risk of hysteresis effects.

[0094] There are commercially available concentrates that can be used in the fluid generation systems 20 described herein.

[0095] In some embodiments, a dialysis solution for the treatment of CKD patients by hemodialysis, hemofiltration or hemodiafiltration is produced by mixing a single concentrate with water at a dilution ratio of 10-50 by volume. In a non-limiting example, the single concentrate includes lactate, sodium, potassium, calcium, magnesium, glucose and chloride. Such concentrates are commercially available, for example, from NxStage for the PureFlow SL system. Alternatively, the dialysis solution may be produced by mixing two concentrates with water. For example, a bicarbonate concentrate and an acid concentrate may be mixed with water at a dilution ratio of 10-50. Such concentrates are commercially available and well known in the art. In a non-limiting example, the bicarbonate concentrate includes bicarbonate and the acid concentrate includes sodium, potassium, calcium, magnesium, glucose, acetate and chloride. In some acid concentrates, the acetate is replaced or supplemented by another acid, for example, citric acid or hydrochloric acid.

[0096] In some embodiments, a dialysis solution for CRRT treatment of AKI patients is produced by mixing at least one concentrate with water. In a non-limiting example, such a dialysis solution includes bicarbonate, sodium, potassium, calcium, magnesium, phosphate, glucose, acetate, and chloride. In one example, a base concentrate and an electrolyte concentrate can be mixed with water to form the dialysis solution. For example, the base concentrate can be an alkaline bicarbonate solution and the electrolyte concentrate can be an acidic glucose-based electrolyte solution.

[0097] In some embodiments, a dialysis solution for use in peritoneal dialysis (PD) is produced by mixing at least one concentrate with water. Exemplary compositions of PD concentrates to be mixed with water, individually or in combination, are disclosed in US2018 / 0021501 and WO2017 / 193069, which are incorporated herein by reference.

[0098] While the subject matter of the present disclosure has been described in connection with what are presently considered to be the most practical embodiments, the subject matter of the present disclosure should not be limited to the disclosed embodiments, but on the contrary, it is insufficient to cover various modifications and equivalent arrangements that are included within the spirit and scope of equivalents of the appended claims.

[0099] Additionally, although acts are shown in the figures in a particular order, this should not be construed as requiring that such acts be performed in the particular order shown, or in sequential order, or that all of the shown acts be performed, to achieve desirable results.

[0100] Below, sections are listed to summarize some of the aspects and embodiments discussed above.

[0101] C1. A computer-implemented method for producing a medical fluid for renal replacement therapy, the method comprising: operating (402) a first pump (P1) to transport a first fluid (F1) from a first container (3a) arranged on a first scale (2a) into a supply path (4a) extending to an outlet (19d) for the medical fluid; operating (403) a second pump (P2) to transport a second fluid (F2) from a second container (3b) arranged on a second scale (2b) into the supply path (4a) to produce a mixture of the first fluid and the second fluid (F1, F2) in the supply path (4a); measuring (404) a composition-related parameter of the mixture by a sensor (22); and operating the first pump (P1) until the sensor (22) measures a target value of the composition-related parameter. and adjusting (405) a pumping speed of at least one of the first and second pumps (P1, P2); determining (406) a relationship between a first weight change on the first scale (2a) and a second weight change on the second scale (2b) while the sensor (22) is measuring the target value based on a first output signal and a second output signal (S1, S2) from the first scale and the second scale (2a, 2b); and generating (413) the medical fluid in the supply path (4a), wherein the generating (413) includes operating the first pump and the second pump (P1, P2) based on the first output signal and the second output signal (S1, S2) to achieve the relationship between the first weight change and the second weight change. method.

[0102] C2. the first and second pumps (P1, P2) are operated simultaneously to convey the first and second fluids (F1, F2) into the supply path (4a); The method according to C1.

[0103] C3. and prior to said measuring (404), operating (401) a valve device (21a, 21b) to divert said mixture from said supply path (4a) to a bypass path (20; 20a, 20b) which leads said mixture past said sensor (22), The method according to claim C1 or C2.

[0104] C4. and operating (414) the valve arrangement (21 a, 21 b) to direct the medical fluid along the supply path (4 a) to the outlet (19 d) for the medical fluid when the medical fluid is produced in the supply path (4 a). The method according to C3.

[0105] C5. the medical fluid is produced in the supply path (4a) upstream of a connection point where the bypass path (20; 20a, 20b) is joined to the supply path (4a), The method according to C3 or C4.

[0106] C6. the outlet (19d) is connected to a receiving device (40), the method further comprising: detecting (1101) an interrupted operation of the receiving device (40) while the medical fluid is being guided along the supply path (4a) to the outlet (19d); and, upon detecting the interrupted operation, operating (1102) the valve devices (21a, 21b) to close the supply path (4a) and open the bypass paths (20a, 20b); and reducing (1103) the pumping speed of at least one of the first pump and the second pump (P1, P2). Method C4 or C5.

[0107] C7. The reducing (1103) further includes maintaining the relationship between the first weight change and the second weight change. The method according to C6.

[0108] C8. and prior to said operating (402) of said first pump (P1) and said operating (403) of said second pump (P2), having a user fluidly connect said bypass path (20; 20a, 20b) to said sensor (22). The method according to any one of C3 to C7.

[0109] C9. and initiating (803) a procedure to ensure reuse of the sensor (22) after completion of the renal replacement therapy. The method according to C8.

[0110] C10. the steps for ensuring reuse include at least one of: a) operating a fluid supply device (17; 1b) comprising the sensor (22) to perform an operation for cleaning and / or disinfecting the sensor (22); or b) conveying a dedicated fluid through a bypass path (20; 20a, 20b) and having the user disconnect the bypass path (20) from the sensor (22) and operate the sensor (22) to retain the dedicated fluid within the sensor (22), The method according to C9.

[0111] C11. The dedicated fluid is bacteriostatic; The method according to C10.

[0112] C12. Conveying the dedicated fluid includes operating the second pump (P2) to convey the second fluid (F2) to the sensor (22) via the supply path (4a) and the bypass path (20; 20a, 20b), or operating a third pump (P3) to convey a third fluid (F3) to the sensor (22) via the supply path (4a) and the bypass path (20b), the third fluid (F3) being included in the medical fluid together with the second fluid (F2). The method according to C10 or C11.

[0113] C13. The supply pathway (4a) is discarded after completion of renal replacement therapy; 2. A method according to any of the preceding claims.

[0114] C14. producing (413) the medical fluid includes controlling pumping speeds of the first and second pumps (P1, P2) to produce the medical fluid at a target flow rate while maintaining the relationship between the first weight change and the second weight change. 2. A method according to any of the preceding claims.

[0115] C15. the target flow rate corresponds to a consumption rate of the medical fluid by the renal replacement therapy; The method according to C14.

[0116] C16. The first fluid (F1) is water and the second fluid (F2) is a liquid concentrate; 2. A method according to any of the preceding claims.

[0117] C17. said adjusting (405) including adjusting the pumping speed of said second pump (P2) until said sensor (22) measures said target value of said composition-related parameter; The method according to C16.

[0118] C18. monitoring (416, 417) the pumping speeds of the first and second pumps (P1, P2) while the medical fluid is being produced in the supply path (4a) to detect changes indicative of operational errors. 2. A method according to any of the preceding claims.

[0119] C19. operating (408) a third pump (P3) for conveying a third fluid (F3) from a third container (3c) arranged on a third scale (2c) to the supply path (4a), wherein the first pump (P1) is operated to convey the first fluid (F1) into the supply path (4a) and / or the second pump (P2) is operated to convey the second fluid (F2) into the supply path (4a), generating a further mixture in the supply path (4a); measuring (409) the composition-related parameter of the further mixture by the sensor (22), wherein the sensor (22) determines a further object of the composition-related parameter. and adjusting (410) the pumping speed of the third pump (P3) until the sensor (22) measures the further target value, and determining (411) a further relationship between a third weight change on the third scale (2c) and at least one of the first weight change and the second weight change based on a third output signal (S3) from the third scale (2c) while the sensor (22) measures the further target value, wherein the generating (414) includes operating the third pump (P3) based on the third output signal (S3) to achieve the further relationship between the third weight change and the at least one of the first weight change and the second weight change. 2. A method according to any of the preceding claims.

[0120] C20. During the adjusting (410), the first pump and the second pump (P1, P2) are operated simultaneously to deliver the first fluid and the second fluid (F1, F2) to the supply path (4a), and the pumping speeds of the first pump and the second pump (P1, P2) are fixed to achieve the relationship between the first weight change and the second weight change. The method according to C19.

[0121] C21. The composition-related parameter represents the conductivity, resistivity, or concentration of one or more solutes, or pH; 2. A method according to any of the preceding claims.

[0122] C22. The medical fluid is a treatment fluid for use in extracorporeal blood therapy or peritoneal dialysis therapy. 2. A method according to any of the preceding claims.

[0123] C23. a control device comprising: a circuit (31, 32) configured to perform the method according to any one of C1 to C22; and a signal interface (33a) configured to output control signals (C1, C2) for the first and second pumps (P1, P2) and further configured to receive the first and second output signals (S1, S2) from the first and second scales (2a, 2b) and a sensor signal (S5) representative of the composition-related parameter from the sensor (22), Control device.

[0124] C24. A computer instruction that, when executed by a processor (31), causes the processor (31) to execute any one of the methods described in C1 to C22. Computer-readable medium.

[0125] C25. A system for producing a medical fluid for renal replacement therapy, the system comprising a first scale (2a), a first container (3a) arranged on the first scale (2a), a second scale (2b), a second container (3b) arranged on the second scale (3b), a supply path (4a) configured to receive a first fluid (F1) from the first container (3a) and a second fluid (F2) from the second container (3b) and extending to an outlet (19d) for the medical fluid. ), a first pump (P1) arranged to transport the first fluid (F1) from the first container (3a) to the supply path (4a), a second pump (P2) arranged to transport the second fluid (F2) from the second container (3b) into the supply path (4a) to generate a mixture of the first and second fluids (F1, F2) in the supply path (4a), a sensor (22) configured to measure a composition-related parameter, and a control device (30) as described in C23, system.

[0126] C26. The sensor (22) is reusable. The system described in C25.

[0127] C27. a bypass path (20; 20a, 20b) fluidly connected to the supply path (4a) and extending to the sensor (22), and a valve arrangement (21a, 21b) operable to selectively direct the mixture from the supply path (4a) to the bypass path (20; 20a, 20b), 20. The system according to claim 19, wherein said system is a

[0128] C28. and an auxiliary sensor (122) configured to measure the composition-related parameter and disposed in the supply path (4 a), and the control device (30) is configured to execute a safety procedure (1300) while producing the medical fluid in the supply path (4 a), the safety procedure (1300) including obtaining measurements indicative of the medical fluid from the auxiliary sensor (112), evaluating the measurements for detection of a deviation, and executing a dedicated action upon detection of the deviation. The system described in C27.

[0129] C29. the auxiliary sensor (122) is a disposable component; The system described in C28.

[0130] C30. the control device (30) is further configured to perform a calibration procedure (1310) while producing the medical fluid in the supply path (4a), the calibration procedure (1310) including operating the valve devices (21a, 21b) to direct the medical fluid from the supply path (4a) to the bypass path (20; 20a, 20b), obtaining a first set of actual measurements indicative of the medical fluid from the sensor (22), obtaining a second set of actual measurements indicative of the medical fluid from the auxiliary sensor (122), and calculating a calibration factor based on the first and second sets of actual measurements, and the control device (30) is configured to adjust the actual measurements by the calibration factor before evaluating the actual measurements in the safety procedure (1300). 2. The system according to claim 1, wherein the first and second components are selected from the group consisting of fluorouracil, fluoro

[0131] C31. a mechanical part (1b) and a disposable device (1a) releasably engaged with said mechanical part (1b), said mechanical part (1b) comprising said first and second scales (2a, 2b), said first and second pumps (P1, P2) and said valve arrangement (21a, 21b), said disposable device (1a) defining said supply path (4a) and said bypass paths (20, 20a, 20b); The system according to any one of C27 to C30.

[0132] C32. the sensor (22) is releasably connected to the bypass path (20; 20a, 20b); The system according to any one of C27 to C31.

[0133] C33. and operable to prompt a user to operate the sensor (22) to convey the dedicated fluid through the bypass path (20; 20a, 20b) and to disconnect the bypass path (20; 20a, 20b) from the sensor (22) and to retain the dedicated fluid within the sensor (22). The system according to any one of C27 to C32.

[0134] C34. The dedicated fluid comprises the second fluid (F2) and / or the third fluid (F3) optionally contained in the medical fluid, and the dedicated fluid is bacteriostatic; The system described in C33.

[0135] C35. the sensor (22) being included in a fluid supply device (17) configured for supplying the first fluid (F1) and fluidly connected to the first container (3 a); The system according to any one of C27 to C34.

[0136] C36. the fluid supply device (17) is operable to perform a cleaning and / or disinfection procedure on the sensor (22); The system described in C35.

[0137] C37. a connecting line (4b) extends from the second container (3a) to a junction (6') on the supply path (4a), the second pump (P2) is arranged in or on the second connecting line (4b) to convey the second fluid (F2) from the second container (3a) to the supply path (4a), and the first pump (Pl) is arranged in or on the supply path (4a) between the junction (6') and the medical fluid outlet (19d); The system according to any one of C25 to C36.

[0138] C38. A disposable device for use in a system according to any one of claims 27 to 38, comprising a first container (3a), a supply path (4a), a connection line (4b) in fluid communication with the supply path (4a) and extending to a first end fluid connector (19b) configured to connect to the second container (3b), and a bypass path (20; 20a, 20b) extending from the supply path (4a) to a second end fluid connector (19f) configured to connect to an inlet connector (23a; 92a) in fluid communication with the sensor (22), Disposable device.

Claims

1. 1. A computer-implemented method for generating a medical fluid for renal replacement therapy, the method comprising: operating (402) a first pump (P1) to convey a first fluid (F1) from a first container (3a) disposed on a first scale (2a) into a supply path (4a) extending to an outlet (19d) for said medical fluid; operating (403) a second pump (P2) to convey a second fluid (F2) from a second container (3b) arranged on a second scale (2b) into the supply line (4a) to generate a mixture of the first fluid and the second fluid (F1, F2) in the supply line (4a); measuring (404) a composition-related parameter of said mixture by a sensor (22); adjusting (405) the pumping speed of at least one of the first pump and the second pump (P1, P2) until the sensor (22) measures a target value of the composition-related parameter; determining (406) a relationship between a first weight change on the first scale (2a) and a second weight change on the second scale (2b) while the sensor (22) is measuring the target value based on a first output signal and a second output signal (S1, S2) from the first scale and the second scale (2a, 2b); and generating (413) the medical fluid in the supply path (4a), the generating (413) including operating the first pump and the second pump (P1, P2) based on the first output signal and the second output signal (S1, S2) to achieve the relationship between the first weight change and the second weight change. method.

2. and prior to said measuring (404), operating (401) a valve device (21a, 21b) to divert said mixture from said supply path (4a) to a bypass path (20; 20a, 20b) which leads said mixture past said sensor (22), The method of claim 1.

3. and operating (414) the valve arrangement (21 a, 21 b) to direct the medical fluid along the supply path (4 a) to the outlet (19 d) for the medical fluid when the medical fluid is produced in the supply path (4 a). The method of claim 2.

4. The outlet (19d) is connected to a receiving device (40), the method further comprising: detecting (1101) an interrupted operation of the receiving device (40) while the medical fluid is being directed along the supply path (4a) to the outlet (19d); operating (1102) the valve devices (21a, 21b) to close the supply path (4a) and open the bypass paths (20a, 20b) upon detecting the interrupted operation; and reducing (1103) the pumping speed of at least one of the first pump and the second pump (P1, P2). The method according to claim 3.

5. The reducing (1103) further includes maintaining the relationship between the first weight change and the second weight change. The method according to claim 4.

6. and prior to said operating (402) of said first pump (P1) and said operating (403) of said second pump (P2), having a user fluidly connect said bypass path (20; 20a, 20b) to said sensor (22).

6. The method according to any one of claims 2 to 5.

7. and initiating (803) a procedure to ensure reuse of the sensor (22) after completion of the renal replacement therapy. The method according to claim 6.

8. The procedure for ensuring reuse includes at least one of: a) operating a fluid supply device (17; 1 b) comprising the sensor (22) to perform an operation of cleaning and / or disinfecting the sensor (22); or b) transporting a dedicated fluid through a bypass path (20; 20a, 20b) and having the user disconnect the bypass path (20) from the sensor (22) and operate the sensor (22) to retain the dedicated fluid in the sensor (22). The method of claim 7.

9. The dedicated fluid is bacteriostatic; The method according to claim 8.

10. Conveying the dedicated fluid includes operating the second pump (P2) to convey the second fluid (F2) to the sensor (22) via the supply path (4a) and the bypass path (20; 20a, 20b), or operating a third pump (P3) to convey a third fluid (F3) to the sensor (22) via the supply path (4a) and the bypass path (20b), the third fluid (F3) being included in the medical fluid together with the second fluid (F2).

10. The method according to claim 8 or 9.

11. monitoring (416, 417) the pumping speeds of the first and second pumps (P1, P2) while the medical fluid is being produced in the supply path (4a) to detect changes indicative of operational errors.

11. The method according to any one of claims 1 to 10.

12. operating (408) a third pump (P3) for conveying a third fluid (F3) from a third container (3c) arranged on a third scale (2c) to the supply path (4a), wherein the first pump (P1) is operated to convey the first fluid (F1) into the supply path (4a) and / or the second pump (P2) is operated to convey the second fluid (F2) into the supply path (4a), generating a further mixture in the supply path (4a); measuring (409) the composition-related parameter of the further mixture by the sensor (22); adjusting (410) the pumping speed of the third pump (P3) until the sensor (22) measures a further target value of the composition-related parameter; determining (411) a further relationship between a third weight change on the third scale (2c) and at least one of the first weight change and the second weight change while the sensor (22) measures the further target value based on a third output signal (S3) from the third scale (2c), the generating (414) includes operating the third pump (P3) based on the third output signal (S3) to achieve the further relationship between the third weight change and the at least one of the first weight change and the second weight change.

12. The method according to any one of claims 1 to 11.

13. during said adjusting (410), said first pump and said second pump (P1, P2) are operated simultaneously to deliver said first fluid and said second fluid (F1, F2) to said supply path (4a), and said pumping speeds of said first pump and said second pump (P1, P2) are fixed to achieve said relationship between said first weight change and said second weight change; The method of claim 12.

14. A control device comprising: a circuit (31, 32) configured to perform the method according to any one of claims 1 to 13; and a signal interface (33a) configured to output control signals (C1, C2) for the first and second pumps (P1, P2) and further configured to receive the first and second output signals (S1, S2) from the first and second scales (2a, 2b) and a sensor signal (S5) representative of the composition-related parameter from the sensor (22). Control device.

15. The method comprises: Computer-readable medium.

16. 1. A system for generating a medical fluid for renal replacement therapy, the system comprising: A first scale (2a); and a first container (3a) placed on the first scale (2a); A second scale (2b); and a second container (3b) placed on the second scale (3b); a supply path (4a) configured to receive a first fluid (F1) from the first container (3a) and a second fluid (F2) from the second container (3b) and extend to an outlet (19d) for the medical fluid; a first pump (P1) arranged to convey the first fluid (F1) from the first container (3a) to the supply line (4a); a second pump (P2) arranged to convey the second fluid (F2) from the second container (3b) into the supply line (4a) to produce a mixture of the first and second fluids (F1, F2) in the supply line (4a); a sensor (22) configured to measure a composition-related parameter; A control device (30) according to claim 15, system.

17. The sensor (22) is reusable.

17. The system of claim 16.

18. a bypass path (20; 20a, 20b) fluidly connected to said supply path (4a) and extending to said sensor (22), and a valve arrangement (21a, 21b) operable to selectively direct said mixture from said supply path (4a) to said bypass path (20; 20a, 20b).

18. A system according to claim 16 or 17.

19. and an auxiliary sensor (122) configured to measure the composition-related parameter and disposed in the supply path (4 a), and the control device (30) is configured to execute a safety procedure (1300) while producing the medical fluid in the supply path (4 a), the safety procedure (1300) including obtaining measurements indicative of the medical fluid from the auxiliary sensor (112), evaluating the measurements for detection of a deviation, and executing a dedicated action upon detection of the deviation.

20. The system of claim 18.

20. the auxiliary sensor (122) is a disposable part; 20. The system of claim 19.

21. The control device (30) is further configured to perform a calibration procedure (1310) while producing the medical fluid in the supply path (4a), the calibration procedure (1310) including: operating the valve device (21a, 21b) to direct the medical fluid from the supply path (4a) to the bypass path (20; 20a, 20b); obtaining a first set of actual measurements indicative of the medical fluid from the sensor (22); obtaining a second set of actual measurements indicative of the medical fluid from the auxiliary sensor (122); and calculating a calibration factor based on the first and second sets of actual measurements, and the control device (30) is configured to adjust the actual measurements by the calibration factor before evaluating the actual measurements in the safety procedure (1300).

21. A system according to claim 19 or 20.

22. a connecting line (4b) extending from the second container (3a) to a junction (6') on the supply path (4a), the second pump (P2) being arranged in or on the second connecting line (4b) for conveying the second fluid (F2) from the second container (3a) to the supply path (4a), and the first pump (P1) being arranged in or on the supply path (4a) between the junction (6') and an outlet (19d) for the medical fluid; 22. A system according to any one of claims 16 to 21.

23. 23. A disposable device for use in a system according to any one of claims 18 to 22, comprising: A first container (3a), The supply path (4a); a connecting line (4b) in fluid communication with said supply path (4a) and extending to a first terminal fluid connector (19b) configured to connect to said second container (3b); a bypass path (20; 20a, 20b) extending from said supply path (4a) to a second terminal fluid connector (19f) configured to connect to an inlet connector (23a; 92a) in fluid communication with said sensor (22), Disposable device.

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