Production of medical fluids for renal replacement therapy

Abstract

A medical fluid for use in the treatment of blood by renal replacement therapy, RRT, is produced in a system (20) comprising pumps (25A, 25B) for pumping liquids from containers (23A, 23B) into a liquid channel (21) for mixing therein. The pumps (25A, 25B) are controlled based on output signals (S1, S2) from scales (24A, 24B) in which the containers (23A, 23B) are arranged so as to achieve a given mixing ratio between the liquids. The system may be constructed by arranging a disposable arrangement in a machine comprising the pumps (25A, 25B) and the scales (24A, 24B). The disposable arrangement may define the liquid channel (21) and the containers (23A, 23B), and the machine may be an RRT device. The system (20) may be operated to produce the medical fluid online for the RRT device.

Description

[Technical field]

[0001] 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 treatment that replaces the normal hemofiltration function of the kidneys. It is used when the kidneys are not functioning adequately, including acute renal failure and chronic kidney disease, known as renal failure. RRT involves the removal of solutes from the blood of patients suffering from renal failure, for example, by dialysis (hemodialysis, HD, or peritoneal dialysis, PD), hemofiltration, or hemodiafiltration. Depending on the modality, RRT can be performed manually or by the use of a machine.

[0003] In RRT, one or more medical fluids of a specific composition are used to treat the blood. Such medical fluids include the so-called dialysis fluids and substitution fluids. Long-term RRT consumes large amounts of medical fluids.

[0004] In some modalities of RRT, pre-made medical fluids are delivered in pre-filled bags to the point of care, e.g., the intensive care unit or the patient's home. The use of large volumes of medical fluids has a significant impact on the environment through transportation. In the intensive care unit, the management and handling of pre-filled bags at the point of care is burdensome for staff, time-consuming and distracts staff from other tasks.

[0005] For example, conventional PD is performed by using pre-filled bags. In HD, different types of machines are used for treating patients with acute kidney injury (AKI) and patients with chronic kidney disease (CKD). HD machines for treating patients with AKI are generally configured to use pre-filled bags of medical fluid, while HD machines for treating patients with CKD are generally built-in with a function of so-called online fluid generation, which generates medical fluid on demand by mixing one or more concentrates with water. In recent years, PD machines with the function of online fluid generation have also been proposed.

[0006] Machines for RRT that have built-in fluid generation capabilities are relatively complex and costly compared to machines for RRT that are configured to use pre-filled bags of medical fluid. Summary of the Invention

[0007] It is an object to at least partially overcome one or more of the limitations of the prior art.

[0008] A further object is to reduce the complexity of machines for producing medical fluids for use in the treatment of blood by RRT.

[0009] Another objective is to reduce the cost of producing medical fluids through the use of machines.

[0010] One or more of these objects, as well as further objects that may become apparent from the following description, are at least partially achieved by a method for generating a medical fluid, a computer readable medium, a system for generating a medical fluid, and a disposable arrangement, as defined by the dependent claims.

[0011] A first aspect is a method of producing a medical fluid for use in treating blood by renal replacement therapy, the method including operating a first pump to pump a first fluid from a first container disposed on a first scale through a first fluid channel, the first fluid being a component of the medical fluid, operating a second pump to pump a second fluid from a second container disposed on a second scale through the second fluid channel into the first fluid channel at a first junction of the first fluid channel and mix the second fluid in the first fluid channel, the second fluid being a component of the medical fluid, and controlling the first and second pumps based on first and second output signals from the first and second scales to achieve a first ratio between a first flow rate of the first fluid into the junction and a second flow rate of the second fluid into the junction.

[0012] The first embodiment controls the production of medical liquid based on measurements by the first and second balances and thus on first and second output signals indicative of the consumption of the first and second liquids. The first and second output signals thereby indicate the change in mass or weight over time and thus contain information on the mass flow rates of the first and second liquids during the production of the medical liquid. The first embodiment thereby provides a simple and well-controlled method of producing medical liquid by controlling the mixing ratio of the first and second liquids based on the flow rates given by the output signals of the balances (gravimetric flow rate measurement). Furthermore, according to the first embodiment, the second liquid is mixed in the first liquid channel itself. The first embodiment is based on the insight that sufficient mixing can be achieved in the first liquid channel without the need for a conventional mixing tank or the like. The mixing of the second liquid in the first liquid channel allows the produced medical liquid to be supplied on demand to a downstream device for RRT as required. It also allows a reduction in size, structural complexity and cost of the system producing the medical liquid.

[0013] A second aspect is a computer readable medium comprising computer instructions which, when executed by a processor, cause the processor to perform the method of the first aspect or any of its embodiments.

[0014] A third aspect is a system for producing a medical fluid for use in renal replacement therapy blood treatment, the system comprising a first scale, a first container disposed on the first scale, a first liquid channel disposed to receive the first liquid from the first container, a first pump disposed to pump a liquid through the first liquid channel, a second scale, a second container disposed on the second scale and connected at a junction to the first liquid channel by the second liquid channel, and a second pump disposed to pump the second liquid from the second container through the second liquid channel and into the first liquid channel and mix the second liquid in the first liquid channel.

[0015] The second and third aspects share technical advantages with the first aspect.

[0016] A fourth aspect is a disposable arrangement for attachment to a device, the disposable arrangement comprising a first container configured to be attached to a first scale of the device, a first liquid channel adapted to receive a first liquid from the first container, and a second liquid channel connected to a junction of the first liquid channel, the first liquid channel defining a first engagement portion for engagement with a first pump of the device upstream of the junction, and the second liquid channel defining a second engagement portion for engagement with a second pump of the device for pumping the second liquid through the second liquid channel into the first liquid channel and mixing the second liquid in the first liquid channel. The first and second liquids are components of a medical liquid for use in the treatment of blood by renal replacement therapy, and the disposable arrangement is operable to generate the medical liquid in the first liquid channel when attached to the device.

[0017] The disposable arrangement of the fourth aspect provides a simple way to enable the device to be configured for the production of medical fluid. Any existing device comprising a first and a second scale and a first and a second pump can be combined with the disposable arrangement to provide a new function of generating medical fluid. For example, scales are common in RRT machines configured for so-called CRRT (Continuous Renal Replacement Therapy) and used for the treatment of patients with AKI. The fourth aspect provides a simple and cost-effective technique for generating medical fluid, and is realized to eliminate the need for a liquid generation unit built into the device. The medical fluid may be generated online, meaning that the medical fluid is provided to an ongoing RRT that consumes the medical fluid at the rate at which it is generated. The ongoing RRT may be performed by the device itself or by a separate device for the RRT. Alternatively, the medical fluid may be generated for storage in one or more containers and then dispensed for use in the RRT. The disposable device arrangement also reduces or eliminates the need for regular disinfection of the device, which is necessary in any device with an integrated (permanent) unit for the production of medical fluid.

[0018] Further objects, aspects and advantages, as well as features and embodiments, may become apparent from the following detailed description, the appended claims, and the drawings. [Brief description of the drawings]

[0019] [Figure 1] FIG. 1 is a schematic diagram of an exemplary system for producing dialysate. [Figure 2A] , [Figure 2B] FIG. 2A is a flow chart of an exemplary method of generating a medical fluid for use in renal replacement therapy (RRT), and FIG. 2B is a flow chart of an exemplary preparation process for RRT. [Diagram 3]3A is a front view of an exemplary apparatus for RRT, FIG. 3B is a plan view of an exemplary disposable arrangement for installation in the apparatus of FIG. 3A, and FIG. 3C is a plan view of an exemplary mixing injection device in the system of FIG. 1. [Figure 4] FIG. 4 is a flow chart of an exemplary method of operating the system of FIG. [Figure 5A] , [Figure 5B] 5A-5B are schematic diagrams of modifications of the system of FIG. [Figure 6] FIG. 6 is a flow chart of an exemplary validation procedure. [Figure 7] 7A-7B are exemplary graphs of pump speed as a function of time during a validation procedure. [Figure 8] FIG. 8 is a schematic diagram of an exemplary extracorporeal blood circuit for RRT. [Figure 9] FIG. 9 shows a modification of FIG. [Figure 10] FIG. 10 shows a further variation of FIG. [Figure 11] FIG. 11 is a flow chart of an exemplary procedure performed by the system of FIG. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0020] DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS The embodiments will now be described more fully 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 numbers refer to like elements throughout.

[0021] It will also be understood that, where possible, any of the advantages, features, functions, devices, and / or operational aspects of any of the embodiments described and / or contemplated herein may be included in any of the other embodiments described and / or contemplated herein, and / or vice versa. Additionally, 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" are intended to 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 word or necessary implication, the word "comprise" or variations such as "comprises" or "comprising" are used in an inclusive sense, i.e., to specify the presence of stated features but not to exclude the presence or addition of further features in various embodiments.

[0022] 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 a second element, and similarly, a second element can be a first element, without departing from the scope of the present disclosure. As used herein, the terms "multiple," "plural," 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.

[0023] As used herein, "HD machine" refers to any machine dedicated to treating patients with AKI, known in the art as "acute dialysis," and / or patients with CKD, known in the art as "chronic dialysis." Some embodiments are particularly suited to HD machines for acute dialysis, because such HD machines typically include a set of scales.

[0024] As used herein, "medical fluid" refers to any fluid that may be supplied for use in blood treatment by renal replacement therapy (RRT), including dialysis fluid, replacement fluid (also known as substitution fluid), or any other infusion fluid. Note that such medical fluids are supplied for use in the treatment of blood and are therefore distinct from such blood. As used herein, RRT includes, but is not limited to, hemodialysis (HD), hemofiltration (HF), hemodiafiltration (HDF), peritoneal dialysis (PD), and the like. The following description is applicable to any medical fluid that may be used for blood treatment by any form of RRT.

[0025] 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.

[0026] FIG. 1 is a schematic diagram of an exemplary system 20 for producing a medical fluid. The system 20 produces the medical fluid by mixing a first liquid with a second liquid. The first and second liquids are thus components of the medical fluid. The following description assumes that the first liquid is water, the second liquid is a liquid concentrate, and the medical fluid is a dialysis fluid for use in HD. The system 20 is configured to receive water from a source 10 configured to provide water of a required quality, for example in terms of contaminants, bacterial cell count, and endotoxins. The water source 10 may be a centralized system or a local stand-alone device connected to a tap water outlet.

[0027] The system 20 comprises a first liquid channel 21 ("main channel") extending from the source 10 to the hemofilter ("dialyzer") 30. A first container 23A is in fluid communication with the main channel 21 via a first connecting liquid channel 22A that connects to the main channel 21 at a junction 26A. A control valve 27 is disposed in the main channel 21 between the source 10 and the first connecting liquid channel 22A to control the inflow of water into the system 20. The container 23A is disposed on a scale 24A configured to provide a measurement signal or output signal S1 indicative of the weight of the container 23A. The container is shown here hanging on a hook-like member of the scale, but may alternatively be mounted on the scale. The system 20 further comprises a subsystem for supplying a concentrate to the main channel 21. The subsystem includes a second container 23B that contains the concentrate. The container 23B is disposed on a scale 24B configured to provide a measurement signal or output signal S2 indicative of the weight of the container 23B. The reservoir 23B is in fluid communication with the main channel 21 via a second connecting liquid channel 22B. The liquid channel 22B is connected to the main channel 21 at a junction 26B.

[0028] The system 20 further comprises two liquid pumps. A first liquid pump 25A is arranged in or on the main channel 21, intermediate junctions 26A, 26B, for pumping water along the main channel 21 towards junction 26B. A second liquid pump 25B is arranged to pump concentrate from the vessel 22B towards junction 26B and thus into the main channel 21. In the following, the flow rates of water and concentrate into junction 26B are respectively referred to as Q and Q, as indicated in brackets in FIG. A and Q B The resulting dialysate flow rate is Q AB 3C. The water and concentrate liquid streams join at junction 26B and are mixed within main channel 21 downstream of junction 26B. Although not shown in FIG. 1, system 20 may include one or more devices configured to promote mixing, for example, inside junction 26B or downstream of junction 26B in main channel 21. In some embodiments, junction 26B is a three-way connector. Further details are provided below with reference to FIG. 3C.

[0029] In the variation included in FIG. 10 (described below), the main channel 21 extends from a container 23A that is in fluid communication with the source 10 via a separate liquid channel 29, and a control valve 27 is disposed in the separate liquid channel 29 to control the inflow of water into the system 20.

[0030] In another variation, also included in FIG. 10, the first liquid pump 25A is instead disposed in or on the main channel 21 downstream of the junction 26B. The pump 25A thereby AB Define Q B As defined by pump 25B, Q A Indirectly defines

[0031] 1, system 20 further includes a sampling port 28 downstream of junction 26B. Sampling port 28 may be of any conventional configuration that provides access to main channel 21 for extraction of a sample of the liquid therein.

[0032] 1, a sensor 36 may be disposed within main channel 21 to measure the conductivity of the liquid passing therethrough or the concentration of one or more substances in the liquid passing therethrough. As shown, sensor 36 provides a measurement or output signal S3.

[0033] In a further variation, not shown in Fig. 1, system 20 further comprises one or more sterilizing grade filters, for example in main channel 21 downstream of junction 26B. The filters may be configured to ensure that the medical fluid meets the standards of an ultrapure dialysis fluid or substitution fluid in terms of viability (sterility) and endotoxins. Such filters are well known in the art.

[0034] In Fig. 1, the system 20 is included in an arrangement for HD treatment and is configured for online generation of dialysate. Online generation, as used herein, means that the production rate of the medical fluid matches the consumption rate of the medical fluid during RRT. The arrangement for HD treatment in Fig. 1 comprises a dialyzer 30 defining first and second compartments 31, 32 separated by a semipermeable membrane 33, as known in the art. A main channel 21 is connected to the first compartment 31 and allows the dialysate to flow through the first compartment 31, as indicated by the arrow, to a waste channel 37 that opens into a drain 38, as shown, or to a container for collecting used dialysate ("waste"). A further pump 25D ("waste pump") is arranged in or on the waste channel 37 to control the flow rate of waste from the dialyzer 30. 1, first and second blood lines 34, 35 are connected to the second compartment 32 to allow blood from the patient to be pumped through the second compartment 32, as indicated by the arrows, whereby the blood is treated in the dialyzer 30. The principles of hemodialysis are well known to those skilled in the art and will not be described further herein.

[0035] In the variation of the system 20 shown in FIG. 9, a bypass channel 121 is added in parallel with the first compartment 31 of the dialyzer 30. The bypass channel 121 establishes an additional fluid path between the main channel 21 and the drain 38. Valve arrangements 27′, 27″ are operable to selectively direct flow in the main channel 21 to the bypass channel 121 instead of to the dialyzer 30. As shown, the sensor 36 may be disposed in the bypass channel 121. Fluid flow is driven into and through the bypass channel 121 by pumps 25A, 25B of FIG. 1.

[0036] In some embodiments, the system 20 is a permanent unit in an apparatus for RRT. In such a permanent unit, the liquid channels 21, 22A, 22B may be defined by tubes or may be configured as passages in a solid block, and the liquid pumps 25A, 25B and the control valve 27 may be of any type. It is understood that the container 23B may be connected to a source of concentrate for refilling, if necessary. Alternatively, the container 23B may be removed and replaced with a filled container when empty. It is understood that such a permanent unit needs to be connected to an apparatus for cleaning and disinfection of the liquid channels and any other components that encounter liquid.

[0037] In some embodiments, the system 20 is a permanent unit of a separate fluid generating device arranged to supply medical fluid to a device for RRT.

[0038] In some embodiments, described in more detail below with reference to Figs. 3A-3B, the system 20 comprises a disposable arrangement defining the liquid channels 21, 22A, 22B and the containers 23A, 23B, and is arranged in engagement with an apparatus or machine comprising other components of the system 20, such as scales, pumps, valves, etc. The machine may be an HD machine, also denoted as a "monitor" in the following, or a liquid generating device separate from the HD machine. In the disposable arrangement, the liquid channels 21, 22A, 22B may be defined by tubes and the containers 23A, 23B may be defined by flexible bags or rigid containers. In some embodiments, the disposable arrangement is made from a plastic material. The liquid pumps 25A, 25B may be peristaltic pumps that engage the outside of the tubes to generate a moving compression of the tubes and move the liquid along the tubes. Conventionally, to enable the use of a peristaltic pump, the tubes are provided with dedicated engagement portions, also known as pump segments, configured to be engaged by compression elements of the peristaltic pump. Similarly, valve 27 may be, for example, a clamp, pinch valve, or the like that engages the outside of the tubing to control flow through the tubing by selectively compressing the tubing to prevent the passage of liquid therethrough.

[0039] As shown in FIG. 1, a control device 40 is provided to control the operation of the system 20. If the system 20 is operated by a HD machine, the control device 40 may be a controller of the HD machine or may be a separate controller. In the illustrated example, the control device 40 is configured to generate control signals C1 for the valve 27, C2, C3 for the pumps 25A, 25B according to a control program including computer instructions. The control program is also configured to operate based on measurement signals S1-S3 received by the control device 40 from the scales 24A, 24B and the sensor 36 (if present). The control device 40 comprises a processor 41 and a computer memory 42. The control program is stored in the memory 42 and executed by the processor 41. The control program may be provided to the control device 40 on a computer-readable medium, which may be a tangible (non-transitory) product (e.g., a magnetic medium, an optical disk, a read-only memory, a flash memory, etc.) or a propagating signal. In the illustrated example, the control device 40 comprises a signal interface 43A for providing control signals to the system 20 and receiving measurement signals from the system 20. The control device 40 also comprises an input interface 43B for connecting to one or more input devices 44 that allow a user to input control data, and an output interface 43C for connecting to one or more output devices 45 for providing feedback data to the user. For example, the input devices 44 may comprise a keyboard, a keypad, a computer mouse, control buttons, a touch screen, a printer, a microphone, etc., and the output devices 45 may comprise a display device, a touch screen, an indicator lamp, an alarm device, a speaker, etc. The user may be a person with clinical experience, such as a doctor or a nurse, or a patient.

[0040] It will be appreciated that control device 40 may be configured to generate additional control signals and receive additional measurement signals. For example, if system 20 is part of an HD machine, control device 40 may generate control signals for additional pumps, valves, etc. within the HD machine, as shown by control signal C4 for waste pump 25D in FIG.

[0041] FIG. 2A is a flow chart of an exemplary method 200 of operating the system of FIG. 1 to generate dialysis fluid. The method 200 may be executed by the control device 40 via the control signals C1-C3. The method 200 assumes that water has entered the first container 23A from the source 10 by opening the valve 27. In step 201, the pump 25A operates to pump a first liquid (here water) from the container 23A through the main channel 21. In step 202, the pump 25B operates to pump a second liquid (here concentrate) from the container 23B through the connecting liquid channel 22B into the main channel 21 at the junction 26B so that the second liquid in the main channel mixes. Step 204 controls the pumps 25A, 25B based on the measurement signals S1, S2 from the scales 24A, 24B to control a first flow rate (Q A ) and the second flow rate (Q B 1. The control device 40 may determine the ratio of the concentrate to the water in a desired mixing ratio ...

[0042] The method 200 provides a simple and well-controlled technique for producing dialysate by step 204 performing open-loop or closed-loop control of the pumps 25A, 25B based on the measurement signals S1, S2.

[0043] When the first liquid is water, step 204 effectively dilutes the concentrate from container 23B to achieve the target composition of the dialysate.

[0044] Step 204 may include determining from the signals S1, S2 a first weight change on the first scale 24A during a first time period and a second weight change on the second scale 24B during a second time period while the pumps 25A, 25B are operating. Based on the first and second weight changes and the lengths of the first and second time periods, step 204 may determine a weight change per unit time for each of the first and second scales 24A, 24B. The weight change per unit time may be calculated as a mass flow rate Q A , Q B Then, step 204 calculates a specified ratio, e.g., Q A / Q B = R1 or Q A / Q AB Step 204 may perform open loop control by calculating a calibrated stroke volume for each pump 25A, 25B based on S1 and S2 and setting the speed of each pump to satisfy R1 or R1'. Alternatively, step 204 may perform open loop control by taking into account S1 and S2 and calculating a mass flow rate relationship between Q a and Q B Q satisfies R1 or R1' A and Q B Closed-loop control may be performed by controlling each pump to achieve a target value of . Even greater accuracy may be achieved by performing step 204 to also take into account a measurement signal S3 from sensor 36 (if present) that is indicative of a characteristic of the resulting dialysate. Thus, in response to the measurement signal S3, step 204 may adjust the speed of at least one of pumps 25A, 25B.

[0045] Step 204 also includes, for example, if system 20 is configured for on-line fluid generation, determining the flow rate Q of the resulting dialysate. ABThe pumps 25A and 25B may be controlled to achieve the following: AB This control can be facilitated by placing pump 25A downstream of junction 26B (see FIG. 10).

[0046] Method 200 is not only applicable to mixing two liquids, but may be extended to mixing any number of liquids. As an example of this, method 200 of FIG. 2A includes step 203 of operating a third pump to pump a third liquid, such as another concentrate, from a third container of the second or third scale into the main channel to mix the third liquid in the main channel. An embodiment of step 203, and a corresponding modification of step 204, is illustrated below with reference to FIGS. 5A-5B.

[0047] FIG. 2A also shows that the method 200 may include step 204A of requesting a user to take a sample of the resulting dialysate at a sampling port (28 in FIG. 1) and input composition data of the sample. The composition data may be obtained by conventional analysis of the sample, for example to determine its conductivity or the concentration of one or more substances. The request may be generated at the output device 45 (FIG. 1) and the composition data may be input via the input device 44 (FIG. 1). The method 200 may further include step 204B of updating the control performed by step 204 upon receiving the composition data to adjust one or more properties of the dialysate. For example, step 204B may correct for deviations in the composition of the concentrate in the container 23B from a nominal composition, inaccuracies in the measurements of the scales 24A, 24B, etc. In some embodiments, the method 200 performs steps 204A-204B whenever the container 23B is refilled or replaced.

[0048] FIG. 2B is a flow chart of an exemplary method 220 for performing RRT by using a device, such as the monitor described above. The method 220 is executed by a user of the monitor. In step 221, the user installs a first disposable arrangement on the monitor to define a dialysis circuit. With reference to FIG. 1, the dialysis circuit comprises an extracorporeal blood circuit including a dialyzer 30, a waste line 37, a waste pump 25D, and blood lines 34, 35. Such a first disposable arrangement and its use are well known in the art and will not be described in detail. The first disposable arrangement includes at least a dialyzer 30, a waste line 37, and a line set defining the blood lines 34, 35. The line set may also include a drip chamber, one or more access devices on the blood lines 34, 35 for connection to the patient's blood circulatory system, etc. In step 222, a second disposable arrangement is installed in the monitor to define the liquid generating system 20, and connected to a water source (10 in FIG. 1) and a concentrate container (23B in FIG. 1) if not already included in the second disposable arrangement. An example of the second disposable arrangement and its installation is described below with reference to FIGS. 3A-3B. In step 223, the monitor is operated to simultaneously perform the RRT and generate medical fluid, e.g., dialysis fluid, for use in the RRT. Alternatively, step 221 is omitted and step 223 operates the monitor to generate only medical fluid. In a further alternative, step 222 is omitted and instead the system 20 is integrated into the monitor.

[0049] FIG. 3A shows a schematic example of a monitor 100. The monitor 100 has a chassis 101 mounted on a stand 102, which in this example is provided with wheels to facilitate repositioning of the monitor 100. The scales 24A-24D are arranged on the chassis 101 and connected to protruding hook-like elements on which containers can be placed by a user of the monitor 100. A pump arrangement 25 is provided on the chassis 101 to define a number of peristaltic pumps 25A-25D accessible to the user. The monitor 100 further comprises a set of sensor ports 103 connected to sensors in the chassis 101. The sensors may be configured to measure pressure, temperature, conductivity, etc. In the example of FIG. 3A, the monitor 100 further comprises an air detector 104A, a holder 104B for a dialysis machine, and a set of clamps 105. A control unit 40 is disposed within the chassis 101 and is configured to control the operation of the monitor 100 by obtaining measurement data from the air detector 104A, the sensors and scales 24A-24D, and by selectively activating the pumps 25A-25D and the clamps 105. A touch screen is connected to the control device 40 to form a combined input / output device 44 / 45 for interaction with a user.

[0050] It should be emphasized that the monitor 100 of FIG. 3A is given merely as a non-limiting example. The included components may vary both in function and number. However, it is assumed that the monitor 100 comprises at least two scales, at least two peristaltic pumps, and a clamp. These components realize the scales 24A, 24B, the pumps 25A, 25B, and the valve 27 of the system 20 of FIG. 1. This type of monitor is commonly used to treat patients with acute renal failure, so-called AKI, by acute dialysis. In acute dialysis, patients are typically treated continuously by RRT, this treatment commonly known as CRRT. The continuous nature of acute dialysis requires precise control of the fluid removal ("ultrafiltration"). To precisely monitor and control the removal of fluid, machines for acute dialysis usually have a scale to which a container pre-filled with dialysate and an empty container to receive the waste fluid are attached.

[0051] As mentioned in the Background section, the dispensing and handling of pre-filled containers of dialysis fluid has many inherent drawbacks. These drawbacks can be overcome by the use of a disposable arrangement 120 ("disposable") shown in FIG. 3B. The disposable 120 may be installed in the monitor 100 to define the liquid generating system 20 of FIG. 1. In the example of FIG. 3B, the disposable 120 defines a main channel 21 extending from an inlet connector 21A to an outlet connector 21B. The inlet connector 21A is configured to connect to the source 10 (FIG. 1) and the outlet connector 21B is configured to connect to the dialyzer 30 or the sensor port 103 (see below) of the monitor 100. The disposable 120 further comprises or defines a first container 23A, a first connecting liquid channel 22A, a junction 26B, a second connecting liquid channel 22B and a second container 23B as described with reference to FIG. 1. In the alternative embodiment described above, the inlet connector 21A may instead be separate from the main channel 21 and disposed at the end of a connecting line extending from the first container 23A (see FIG. 10). The disposable 120 further comprises a first engagement portion E1 in the main channel 21 and a second engagement portion E2 in the liquid channel 22B. The engagement portions E1, E2 are configured to be engaged by the respective peristaltic pumps as described above. In a variant, the engagement portion E1 is instead disposed downstream of the junction 26B. As indicated by the dashed lines, the disposable 120 may also include a sampling port 28 as described with reference to FIG. 1. Although not shown, the disposable 120 may also include a sensor 36 and / or a bypass channel 121 (FIGS. 9-10) and / or a waste line 37 and / or a sterilization grade filter as described above.

[0052] According to step 222 of FIG. 2B, the disposable 120 may be installed in the monitor 100 to define the system 20. At this time, the first container 23A is empty and the second container 23B is filled with concentrate. The disposable 120 may be delivered as a single component or as parts that are joined by the user before or during installation of the disposable 120 on the monitor 100. For example, the second container 23B may be delivered separately and attached by the user to the connector 22B' at the end of the liquid channel 22B.

[0053] Installation of the disposable 120 of Fig. 3B on the monitor of Fig. 3A includes suspending the container 23A on the scale 24A, suspending the container 23B on the scale 24B, attaching the connector 22B' to the container 23B, arranging the engagement part E1 on the pump 25A, arranging the engagement part E2 on the pump 25B, and arranging the main channel 21 on the clamp 105, thereby acting as the valve 27 of Fig. 1. Furthermore, the inlet connector 21A can be connected to a source 10, which may be separate from the monitor 100, and the outlet connector 21B can be connected to the dialyzer 30. If the disposable 120 comprises a bypass channel 121 (Fig. 9), the main channel 21 and the bypass channel 121 can be arranged on two further clamps 105, thereby forming the valve arrangement 27', 27'' of Fig. 9. If the disposable item 120 includes a sensor 36 (FIG. 1), a wire of the sensor 36 may be connected to a data input port (not shown) of the monitor 100 to transfer the signal S3 to the monitor 100. In a variant, if the sensor 36 is available in the monitor 100, the outlet connector 21B may be connected to a dedicated sensor port 103 of the monitor 100, and an outlet port (not shown) of the monitor 100 may be connected in fluid communication with the dialyzer 30. Thereby, the dialysate produced by the system 20 is directed through the sensor 36 via the sensor port 103 and through the outlet port to the first compartment 31 (FIG. 1) of the dialyzer 30.

[0054] It will be appreciated that the monitor 100 must have sufficient components to accommodate both the first and second disposable arrangements. For example, in addition to the components required for installation of the disposable device 120 of Fig. 3B, installation of the first disposable arrangement (step 221 of Fig. 2B) may require at least two empty pumps to operate as the waste pump (see 25D of Fig. 1) and blood pump of the extracorporeal blood circuit, and at least one empty scale to which an empty container is attached to receive the waste fluid.

[0055] An exemplary operation of the system 20 of FIG. 1 is described with reference to the flow chart of FIG. 4 after the disposable 120 (FIG. 3A) is attached to the monitor 100 (FIG. 3B). The initial state of the system 20 is that the first container 23A is empty and the second container 23B holds a certain amount of concentrate. In a first step, not shown in FIG. 4, the valve 27 is opened to fill the first container 23A with water while the pump 25A is stopped. When a predetermined amount of water has entered the container 23A, as indicated by the balance 24A, the valve 27 is closed. The system 20 then operates according to steps 201-204, and optionally steps 204A-204B, as described with reference to FIG. 2A. As mentioned above, step 204 determines the mass flow rate Q A and Q B and, optionally, the dialysate flow rate Q AB The pumps 25A, 25B may be operated to achieve target values ​​for the concentrate. Any of these target values ​​may be changed at any point during operation. The expected composition of the resulting dialysate may be calculated and displayed to the user on the output device 45 if the control device 40 has information about the composition of the concentrate.

[0056] In FIG. 4, operation of the system 20 includes a first check procedure for refilling the first container 23A, indicated by steps 205-208, and a second check procedure for replacing the second container 23B, indicated by steps 209-213.

[0057] The first check procedure includes a step 205 of evaluating the measurement signal S1 from the scale 24A to detect the need to refill or replenish the container 23A. For example, step 205 can compare the current weight measured by the scale 24A with a reference weight and determine the need for refilling when the current weight falls below the reference weight. The reference weight can be predefined or set in relation to the weight of the container 23A at the start of the system 20, i.e. when empty. If the need for refilling is not detected, step 206 returns the procedure to step 204. Otherwise, step 206 proceeds to step 207, which stops the pumps 25A, 25B, thereby temporarily stopping the flow of dialysis fluid. If the RTT is performed simultaneously with the production of fluid, the waste pump 25D can also be stopped. After step 207, in step 208, the valve 27 is opened to fill the container 23A with water. Once a predetermined amount of water has entered vessel 23A, as indicated by scale 24A, valve 27 is closed and the procedure then starts the pump and returns to step 204.

[0058] The second check procedure includes a step 209 of evaluating the measurement signal S2 from the scale 24B to detect the need to replace the container 23B. For example, step 205 can compare the current weight measured by the scale 24B with a reference weight and determine the need for refilling when the current weight falls below the reference weight. The reference weight can be predefined or set in relation to the weight of the container 23B at the start of the system 20, i.e. when it is full. If the need for refilling is not detected, step 210 returns the procedure to step 204. Otherwise, step 210 proceeds to step 211 and stops the operation similarly to step 207. After step 211, the user is instructed via the output device 45 to detach the container 23B and install a new full container 23B (step 212). The system 20 then waits for a confirmation by the user via the input device 44. If confirmation is received (step 213), optionally providing that scale 24B has measured sufficient weight, the procedure starts the pump and returns to step 204. If the weight measured by scale 24B is too low or if step 213 waits too long (times out), new instructions can be provided by step 212.

[0059] 3C is a schematic diagram of a junction 26B implemented by a three-way connector defining an internal manifold with three ports 261, 262, 263. Sections 21', 21'' of main channel 21 are connected to ports 261, 262 and section 22' of connecting liquid channel 22B is connected to port 263. Sections 21', 21'', 22' may be permanently or removably connected to ports 261, 262, 263 and may be configured as tubes. The input flows (Q A , Q B ) join together in the internal manifold and form a combined flow (Q AB) into the internal manifold 20. The three-way connector 26B includes a device 264 for promoting or enhancing mixing of the incoming flows. The mixing promotion device 264 may be configured to increase the Reynolds number of either the resultant flow and / or the incoming flows. In some embodiments, the mixing promotion device 264 may be configured to generate or increase turbulence downstream of the device 264. In some embodiments, the device 264 defines a constriction that forms a passageway that is reduced in cross section and then expanded, and may be located anywhere within the internal manifold. Non-limiting examples of three-way connectors with mixing promotion devices are disclosed in International Publication No. WO 2009 / 030973, which is incorporated herein by reference. This known three-way connector is configured for the injection of solutions into blood, but one skilled in the art may adapt the teachings to lower viscosity liquids and flow rates used in the system 20. In a variant, the mixing promotion device 264 may be separate from the junction 26B and located downstream of the junction 26B. Such a separate device 264 may be configured in the same manner as the integrated device described above, or alternatively, the separate device 264 may be configured as a conventional static mixer or a recirculation circuit through which the composite stream is circulated and facilitates mixing before being delivered to the dialyzer.

[0060] In some embodiments, the mixing promotion device 264 is configured to ensure efficient and immediate mixing of the liquids. In other embodiments, depending on, for example, the distance between the junction 26B and the dialyzer 30, or the type of RRT, a lesser or slower degree of mixing may be acceptable as long as the liquids are sufficiently mixed when they reach the dialyzer 30. For example, CRRT is currently considered to be more tolerant of incomplete mixing. However, the degree of mixing required may also depend on the chemical properties of the liquids. For example, as illustrated with reference to Figures 5A-5B, when two concentrates are mixed with water, in the event of incomplete mixing, local chemical instability may occur. For example, the bicarbonate concentrate may tend to precipitate with the calcium of the other concentrate if mixing is incomplete.

[0061] FIG. 5A shows a system 20 configured to produce a dialysis solution by mixing three liquids. The following description focuses only on the differences with the system 20 of FIG. 1. In comparison with FIG. 1, the system 20 comprises a third balance 24C, a third container 23C of the third balance 24C, and a third connecting liquid channel 22C extending between the third container 23C and a second junction 26C of the main channel 21 downstream of the junction 26B. A liquid pump 25C is arranged to pump the third liquid from the third container 23C towards the junction 26C and thus into the main channel 21. The junction 26C receives a combined flow of the first and second liquids, with which the third liquid is mixed. In the following, the flow rate of the combined flow from the junction 26B is referred to as Q, as shown in brackets in FIG. 5A. AB and the flow rate of the third liquid is Q C and the resulting flow rate of the dialysate is Q ABC Junction 26C may have the same configuration as junction 26B, for example as described with reference to FIG. 3C. In the following, it is assumed that the first liquid is water and the second and third liquids are first and second liquid concentrates that are components of a dialysis solution. Any concentrates known in the art may be used.

[0062] As mentioned above, the method 200 of FIG. 2 is also applicable to mixing three liquids. In the example of FIG. 5A, step 203 operates pump 25C to pump the second concentrate from container 23C through third connecting liquid channel 22C into main channel 21, where the second concentrate mixes. A and Q B In addition to controlling pumps 25A, 25B to achieve a first ratio between the first concentrate and the second concentrate, step 204 controls pump 25C based on signal S4 from scale 24C to control the flow rate of the first concentrate (Q B ) and the flow rate of the second concentrate to the second junction 26C (Q C) to achieve a second ratio between the dialysis fluid prescription. The control of pump 25C may be performed similarly to the control of pumps 25A, 25B. Note that pump 25C may be set relative to either pump 25A, 25B to achieve the second ratio. Finally, step 204 controls pumps 25A, 25B, 25C to achieve a Q ratio that is compatible with the dialysis fluid prescription. A , Q B , Q C As will be appreciated, step 204 also involves determining the relationship (mixing ratio) between the resulting dialysate for a given flow rate Q of the dialysate, for example if system 20 is configured for online fluid generation. ABC The pumps 25A, 25B, and 25C may be controlled to achieve this.

[0063] To operate the system 20 of Fig. 5A, the control device 40 of Fig. 1 is further configured to receive the measurement signal S4 from the scale 24C and to output a control signal C5 for the pump 25C. Furthermore, the operation according to Fig. 4 corresponds to the second check procedure, but may include a third check procedure of evaluating the signal S4 from the scale 24C to detect the need to replace the container 23C.

[0064] It should also be understood that the system 20 of Fig. 5A may be implemented by a modified version of the disposable arrangement 120 of Fig. 3B ("extended disposable"). Compared to the disposable of Fig. 3B, the extended disposable further comprises a liquid channel 22C, a second junction 26C, and a third engagement portion of the liquid channel 22C. The third engagement portion is configured to engage with a pump 25C. A third container 23C filled with a second concentrate may be connected or connectable to the liquid channel 22C.

[0065] In a variation of the extended disposable and system of FIG. 5A, fluid channel 22C is fluidly connected to fluid channel 22B or first junction 26B, and second junction 26C is omitted.

[0066] The system of Figure 5A is a simple and straightforward extension of the system of Figure 1. However, it assumes the availability of an additional scale 24C. There may be situations where an additional scale is not available, for example if the extended disposable is placed in a machine that has only two empty scales for liquid production.

[0067] Figure 5B shows an exemplary system 20 that requires only two scales to mix three liquids. The system of Figure 5B is structurally different from the system of Figure 5A only in that the second and third containers 23B, 23C are disposed on a second scale 24B. Thus, the measurement signal S2 of scale 24B indicates the combined weight of containers 23B, 23C.

[0068] Method 200 is also applicable to system 20 of FIG. 5B. Step 203 operates third pump 25C as described above for the system of FIG. 5A. A and Q B In addition to controlling pumps 25A, 25B to achieve a first ratio between the first concentrate flow rate (Q B ) and the flow rate of the second concentrate to the second junction 26C (Q C In one embodiment, step 204 controls pump 25C to achieve a second ratio between dialysis fluid Q and dialysis fluid Q when second and third pumps 25B, 25C are controlled to achieve the first and second ratios. ABC The flow rate Q that results in the desired (target) flow rate of A Step 204 may further include controlling pump 25A to generate Q according to first and second ratios based on the stroke volumes of the respective pumps 25B, 25C. B and Q C Specifically, step 204 can maintain the relative speeds between the pumps 25B, 25C, resulting in a second ratio between their expected flow rates (given by the product of the speed and stroke volume of each pump). A and QB The speeds of the pumps 25A, 25B may be further set while maintaining the relative speed between the pumps 25A, 25B to achieve a first ratio between the pumps 25A, 25B and the pumps 25C. The stroke volume may be predefined or measured for each pump 25B, 25C. For example, a calibration value for stroke volume may be determined during a calibration procedure by operating only one of the pumps 25B, 25C, performing the number of strokes per unit time ("pumping speed"), and determining the corresponding weight change ("mass flow rate") from the signal S2. As used herein, stroke volume may be given in terms of volume or mass per pumping stroke. In the above example, stroke volume by mass may be calculated by dividing the mass flow rate by the pumping speed.

[0069] Step 204 considers S1 and calculates Q A and by controlling pump 25A to achieve a target value of Q B +Q C A closed-loop control can be performed by jointly controlling pumps 25B, 25C taking into account S2 to achieve a target value of . Step 204 can also consider a measurement signal S3 from sensor 36 (if present). Thus, depending on the measurement signal S3, step 204 may adjust the speed of at least one of pumps 25A, 25B, 25C.

[0070] The system of Figures 5A-5B may alternatively be modified to place pump 25A downstream of junction 26C. ABC Define and indirectly define Q A The method 200 controls the pumps 25A, 25B, and 25C to determine Q A , Q B , Q C It will be understood that this arrangement of pumps 25A is equally applicable to achieve any desired mix ratio between.

[0071] To operate the system 20 of FIG. 5B, the control device 40 of FIG. 1 is further configured to output a control signal C5 for the pump 25C. The first and second check procedures of FIG. 4 may also be used in the system of FIG. 5B. For example, if the second and third containers 23B, 23C are expected to run dry at approximately the same time, the second check procedure may infer and signal the need to replace both containers 23B, 23C when the current weight measured by the scale 24B falls below a reference weight. Alternatively, steps 209-210 of the second check procedure may be modified to calculate the cumulative volume of liquid pumped from each container 23B, 23C and to detect the need to refill one of the containers when the cumulative volume of this container exceeds a reference volume. The cumulative volume may be calculated by dead reckoning, for example by counting the number of strokes and multiplying the number of strokes by the stroke volume.

[0072] In FIG. 5B, the flow rate Q B and Q C is controlled by setting the speed of pumps 25B, 25C based on their stroke volumes, B and Q C 6 is included in the method 200 of FIG. 2A and is used to verify that the flow rates Q B and Q C FIG. 6 is a flow chart of a validation procedure 600 that may be performed at least once or intermittently during liquid production to quantify the combined flow rate (Q B +Q C ) but Q BC 7A-7B serve to illustrate the speed of one of the pumps 25B, 25C over time during the procedure 600.

[0073] At the start of procedure 600, pumps 25B, 25C are operated at their respective initial speeds, shown as ω for one pump in FIG. 7A, and flow rates Q B,0 and Q C,0In step 601, a combined flow rate Q is calculated from the measurement signal S2 based on the measured weight change over time. BC This determines the initial combined flow rate Q BC,0 In step 602, the speed of one of the pumps 25B, 25C (the "selected pump") is changed by a predetermined fractional amount α1. This is seen as a step change 71 from ω0 to ω1 in FIG. 7A. The speed may be decreased as shown in FIG. 7A, or it may be increased. The speed of the other pump is fixed throughout the procedure 600. The fractional amount may be any value, for example, in the range of 1-20%. In step 603, the combined flow rate Q BC is again determined from the measurement signal S2, and the first subsequent resultant flow rate Q BC,1 The result is: Then, it may be preferable to reverse the slight change by step 604 returning the selected pump to its initial speed ω0, as shown by step change 72 in FIG. 7A. This limits the effect of procedure 600 on the composition of the dialysate. Procedure 600 then determines the pumping accuracy, i.e., Q BC,0 , Q BC,1 and based on α1, Q B and Q C The evaluation may proceed to step 612, where the accuracy of is evaluated based on the following set of equations, assuming pump 25B is the selected pump: Q BC,0 =ω0 V B +ω C ·V C Q BC,1 =ω1 V B +ω C ·V C =α1 ω0 V B +ω C ·V C V B is the stroke volume of pump 25B, V C is the stroke volume of pump 25C, and ω C is the speed of pump 25C. These equations are used to calculate the stroke volume V B , VC Assume that Q is not changed between steps 601 and 603. BC,0 -Q BC,1 =ω0 V B (1-α1)=Q B,0 Therefore, the flow rate Q at the start of the procedure 600 may be reconstructed as B and Q C may be calculated by step 612. Q B,0 =(Q BC,0 -Q BC,1 ) / (1-α1) Q C,0 =(Q BC,0 -Q B,0 )

[0074] If pump 25C were the pump selected instead, a corresponding set of equations could be given.

[0075] Step 613 then converts the resulting Q B,0 and Q C,0 The value of Q is evaluated with respect to the target value. If a deviation of sufficient magnitude is not found, step 613 proceeds to step 204 (FIG. 2A). Otherwise, if the deviation exceeds the limit value, step 613 proceeds to step 614, where Q B and Q C The speeds of pumps 25B, 25C are modified to better match the target value, and then, in some cases, Q ABC For example, step 614 may modify the speeds of pumps 25A, 25B, and 25C in concert to achieve the target value of Q for the updated stroke volume. B , Q C To generate the target value of stroke volume V B , V C An updated value of Δt may be calculated to set the speed of pumps 25B, 25C. If the deviation is excessive, step 614 may stop liquid production and / or output a warning to the user.

[0076] In the procedure 600, step 602 determines the stroke volume VB , V C 7A, the method may include steps 605-608 which serve to detect when the second subsequent combined flow QBC is changed. In step 605, after the inversion in step 604, the combined flow QBC is determined from the measurement signal S2 in a manner similar to step 601. This results in a second subsequent combined flow QBC, as shown in FIG. BC,2 Step 606 is to obtain Q BC,2 and Q BC,0 Step 606 evaluates the consistency of the stroke volume by comparing the change in stroke volume with Q BC This is based on the recognition that deviations beyond the limits are likely to manifest as hysteresis in the liquid production. If deviations beyond the limits are found, step 607 proceeds to step 608 which may stop liquid production and / or output a warning to the user.

[0077] Procedure 600 may include steps 609 and 611 that serve to compensate for changes in the composition of the dialysate caused by steps 602 and 604. In step 609, the speed of the selected pump is changed by a second small amount, α2. This is seen as step change 73 from ω0 to ω2 in FIG. 7B. The step change of step 609 is made in the opposite direction to the step change of step 602. Thus, if step 602 increases the speed, step 609 decreases the speed and vice versa. Step 611 reverses the second small change to return the selected pump to its original speed, ω0, as shown by step change 74 in FIG. 7B. Steps 609-611 are included to provide the selected pump with an average pumping speed equal to ω0 over the validation procedure 600 as a whole.

[0078] Step 600, like step 601, calculates the combined flow rate Q from the measurement signal S2. BC This may include a step 610 of determining a third subsequent combined flow rate Q BC,3 Step 611 is to obtain Q BC,2 , Q BC,3and α2, thereby providing an over-determined system of equations that may improve the accuracy of steps 612, 614.

[0079] It should be noted that compensation as shown in FIG. 7B and described with reference to steps 609 and 611 of FIG. 6 is merely an example. In one alternative, the pumping speed of the selected pump is varied during compensation. In another alternative, steps 604-608 are omitted and compensation is performed starting at ω1 of FIG. 7B. In general, compensation can be considered to involve varying the pumping speed of the selected pump over a period of time (ΔT in FIG. 7B) to counteract the increase or decrease in the amount of liquid pumped by the selected pump as a result of the first small change by step 602.

[0080] In some embodiments, the system 20 may be operated to direct fluid flow to the bypass channel 121 (FIG. 9) when it is determined that the composition of the dialysate is likely to deviate from the target composition, e.g., during a transient phase such as start-up, or when the target composition changes significantly. For example, fluid flow may be directed through the bypass channel 121 during procedure 600. Additionally, fluid flow may be directed to the bypass channel 121 during the calibration procedure described above to determine calibrated values ​​for the stroke volumes of each pump 25B, 25C.

[0081] FIG. 8 is included to provide a non-limiting example of an extracorporeal blood circuit (EBC) 130 that may be used in combination with the fluid generating system 20. The EBC 130 may be used, for example, in CRRT. In FIG. 8, the EBC 130 is connected to a patient P at a blood removal end and a blood return end. The connections may be made by any conventional device, such as a needle or catheter. The EBC 130 comprises a disposable 131 attached to pumps 132, 135A, 135B of the RRT apparatus (see 100 in FIG. 3A). The disposable 131 comprises blood lines or tubing that define a blood removal pathway 34 and a blood return pathway 35. The dialyzer 30 is connected between the blood removal pathway 34 and the blood return pathway 35. A blood pump 132 is disposed to draw blood from the patient P and pump the blood back to the patient P via the blood compartment of the dialyzer 30. The dialyzer 30 is connected to receive dialysate in the fluid pathway 21 and to output waste in the fluid pathway 37. In the illustrated example, the EBC 130 further comprises a first source of substitution fluid 133A connected by a fluid line 134A to the blood removal pathway 34 intermediate the blood pump 132 and the dialyzer 30. A fluid pump 135A is arranged to pump substitution fluid from the source 133A into the blood removal pathway 34. The EBC 130 further comprises a second source of substitution fluid 133B connected by a fluid line 134B to the blood return pathway 35. The fluid pump 135B is arranged to pump substitution fluid from the source 133B into the blood return pathway 25. In the example of CRRT, the EBC 130 may also include arrangements for infusion of an anticoagulant, such as citrate or heparin, or for infusion of a calcium-containing solution.

[0082] It will be appreciated that the fluid generating system 20 described herein may be connected to provide dialysate to the dialyzer 30 of Figure 8. Alternatively or additionally, substitution fluid may be generated by such a system 20.

[0083] As mentioned above, Figure 8 is merely an example and the EBC 130 includes other conventional components such as clamps, pressure sensors, air detectors, drip chambers, etc. Also, pre-infusion and / or post-infusion of substitution fluid may be omitted.

[0084] There are commercially available concentrates that can be used in the liquid production system 20 described herein.

[0085] In some embodiments, a dialysis solution for the treatment of patients with chronic kidney disease (CKG) by hemodialysis, hemofiltration or hemodiafiltration is produced by mixing a single concentrate with water at a dilution ratio of 10 to 50 times 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 to 50 times. 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.

[0086] In some embodiments, a dialysis solution for CRRT treatment of patients with acute renal failure (AKI) 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.

[0087] 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 that are mixed with water, individually or in combination, are disclosed in U.S. Patent Application Publication No. 2018 / 0021501 and WO 2017 / 193069, which are incorporated herein by reference.

[0088] The foregoing disclosure is equally applicable to the mixing of more than three liquids for the production of a medical fluid. For example, the system 20 of FIG. 5A may be further expanded to include an additional scale for each additional container that is installed. It is also contemplated that two containers may be placed on one scale in FIG. 5A, similar to FIG. 5B. In a further variation, three or more containers may be placed on one scale in FIG. 5A or FIG. 5B.

[0089] Returning to FIG. 1, the control device 40 operates the system 20 based on input control data received via the input interface 43B. The input control data may be at least partially entered manually by a user. In some embodiments, the input control data indicates the concentrates installed in the system and the target composition of the medical fluid to be produced. For example, the input control data may specify a nominal or actual composition of each concentrate, thereby enabling the control device 40 to determine the above-mentioned ratio between concentrate and water to achieve the target composition. In some embodiments, the input interface 43B is connected to a dedicated reader device (see 44), and the nominal or actual composition is provided by the reader identifying a barcode or RFID tag of each container or performing optical character recognition (OCR) of the label of each container. In an alternative embodiment, the respective ratio between the liquids is entered directly by the user. The input control data may also indicate a target value of the flow rate of the medical fluid to be produced. If the system 20 operates for online liquid production, this target value may be provided by a setting of the RRT or a signal indicating the current consumption of medical fluid by the RRT.

[0090] It should also be appreciated that safety features may be included in liquid producing system 20. Such safety features may include the provision of an independent second scale system to allow for detection of malfunctions, the use of keyed connectors to prevent misconnection of containers, the use of different weights for different containers to allow for detection of misconnections, the use of color coding to facilitate correct connection of containers, etc.

[0091] As mentioned above, the system 20 may include a sensor 36 for measuring the conductivity of the produced medical fluid (see FIG. 1). A fluid pump in the system 20 may be controlled to achieve a specified ratio or percentage between the flow rates based on a measurement signal from the scale, and the measured conductivity may be used by a protection function configured to detect deviations and take protective action. Alternatively, a fluid pump in the system 20 may be controlled to achieve a ratio based on a measured conductivity, and the measurement signal from the scale may be used by a protection function. By providing a sensor 36, the system 20 may detect if an incorrect container has been installed and may prevent delivery of a medical fluid with a gross error in composition.

[0092] As discussed with reference to FIG. 2A, the method 200 may include step 204A, which includes the use of the sampling port 28 (see FIG. 1). In an on-line generation, step 204A may, for example, instruct a user to take a sample of the medical fluid and analyze the sample for its content of one or more electrolytes (e.g., sodium, potassium, bicarbonate, etc.) or one or more additives, such as glucose, whenever a new container is installed in the system 20. This composition check request may be ignored or omitted if successive containers relate to the same batch of concentrate. Step 204A may require the user to input the analysis results within a time frame that may be fixed or adjustable, for example, within 30-120 minutes after installation of the new container. The adjustable time frame may be set depending on the dialysis dose, with a larger dialysis dose resulting in a shorter time frame. If the contents are found to deviate significantly from the expected composition, the method 200 may interrupt / pause the RRT and request the user to check whether the concentrate installed is correct. If the deviation is smaller, method 200 may instruct the user to take and analyze a new sample. If the deviation persists in the new sample, method 200 may adjust the ratio in step 204B. If no deviation is found in the new sample, method 200 may proceed to use the current settings for producing the medical fluid.

[0093] The systems and methods for liquid generation described herein are not limited to HD, but apply to any type of RRT. Figure 10 shows an exemplary system 20 for generating medical liquid for any type of RRT. The illustrated system 20 is configured to generate medical liquid by mixing two liquids, but may be extended to mix additional liquids as needed, similar to Figure 5A or Figure 5B. Components in Figures 1 and 10 are identical insofar as they are labeled with the same reference numbers. Such components will not be described again.

[0094] In FIG. 10, the outlet of the main channel 21 is fluidly coupled to a receiving device 30'. The receiving device 30' is configured to receive medical fluid generated in the main channel 21 when the system 20 operates according to the method 200 of FIG. 2A. In some embodiments, the medical fluid is a dialysate for use in extracorporeal blood therapy such as HD or HDF, and the receiving device 30' comprises a dialyzer 30 (FIG. 1) and further conventional components. In some embodiments, the medical fluid is a substitution fluid for use in HF or HDF, and the receiving device 30' comprises an injection port (not shown) in the blood withdrawal path 34 and / or the blood return path 35 (FIG. 1). In some embodiments, the medical fluid is a dialysate for use in PD, and the receiving device 30' comprises a disposable or reusable fluid circuit attached to a PD cycler. As such, the receiving device 30' may also correspond to the peritoneal cavity. In some embodiments, which are applicable to all types of RRT, the receiving device 30' is a reservoir for collecting medical fluid for subsequent use in RRT. In such embodiments, medical fluid is typically not generated on demand. The reservoir may or may not be connected to the device for RRT, or may be part of the device. As shown by the dashed lines, a waste fluid channel 37 may extend from the receiving device 30' to a drain 38, for example, to dispose of waste fluid generated during HD, HDF, HF, or PD.

[0095] Similar to FIG. 9, the system 20 of FIG. 10 comprises a bypass channel 121 defining a liquid path from the main channel 21 to the drain 38. The bypass channel 121 is connected to the main channel 21 upstream of the receiving device 30′. A valve arrangement 27A, corresponding to the valves 27′, 27″ of FIG. 9, is operable to selectively direct the liquid flow in the main channel 21 to the bypass channel 121 instead of the receiving device 30′. The valve arrangement 27A is operated by a control signal C6 from the control device 40 (FIG. 1). A CRP sensor 36 is arranged in the bypass channel 121 to measure a composition-related parameter (CRP) of the liquid passing therethrough and generate a corresponding measurement signal S3. The CRP may indicate a conductivity or an equivalent resistivity. In a variant, the CRP indicates the concentration of a substance in the liquid, in particular a substance present in the unused medical liquid, such as bicarbonate, or an electrolyte, such as sodium, potassium, calcium, magnesium, chloride, etc. If the medical fluid is produced for use in PD, the substance may instead be an osmotic agent such as glucose. In a further alternative, the CRP may indicate the concentration of hydrogen ions, for example in the form of a pH value. Any sensor designated herein by reference numeral 36 may be a CRP sensor.

[0096] Returning to the method 200 of FIG. 2A, the composition of the medical fluid produced by the mixing of the liquids in the main channel 21 depends on the accuracy of the specified ratio between the flow rates of the liquids. As mentioned above, the ratio may be calculated by the control device 40 based on the nominal or actual composition of the liquids involved to achieve a target composition of the medical fluid. Alternatively, the predetermined ratio may be input directly into the control device 40 by a user. However, it may be desirable to automatically determine the ratio of the actual liquids installed in the system. Such an automatic determination is made possible by the system 20 of FIG. 10 through the use of the bypass channel 121 and the CRP sensor 36.

[0097] Figure 11 shows the flow rate Q A , Q B10 is a flow chart of an exemplary tuning procedure 1100 for automatically determining the ratio between the first and second containers 23A and 23B. The tuning procedure 1100 is executed by the control device 40. In step 1101, the valve arrangement 27A operates to close the main channel 21 and open the bypass channel 121. This causes liquid to be directed from the main channel 21 through the bypass channel 121 to the drain 38 while passing the CRP sensor 36. In step 1102, the pump 25A operates to convey the first liquid (water) from the first container 23A through the main channel 21 and into the bypass channel 121. In FIG. 10, it is assumed that the pump 25B is blocked, thereby essentially blocking the liquid channel 22B when not operating. If necessary, a controllable on / off valve (not shown) may be disposed along the liquid channel 22B to selectively block the flow of the second liquid from the second container 23B. In step 1103, the pump 25B operates to convey the second liquid (concentrate) from the second container 23B through the main channel 21 into the bypass channel 121. At this time, the mixture of the first and second liquids passes through the CRP sensor 36. In step 1104, the signal S3 from the CRP sensor 36 is evaluated for the determination of a current CRP value, which is compared with a target CRP value TV, which defines the required characteristics of the medical liquid to be produced. The TV may be predefined and stored in the internal memory 42 of the control device 40, or may be input by a user via the input device 44 (see FIG. 1). If it is found that the current CRP value deviates from the TV, in step 1105 the speed of the pump 25A and / or the pump 25B is adjusted. Steps 1104-1105 are repeated until the current CRP value coincides with the TV. Thus, steps 1104-1105 define a tuning operation. In some embodiments, in step 1105, the desired flow rate Q in the main channel 21 is compared with the desired flow rate Q in the main channel 21. ABThe pump 25A may be adjusted to achieve the TV. If the current CRP value matches the TV, then in step 1106, a weight change relationship (WCR) is determined using the signals S1, S2 from the scales 24A, 24B. The WCR corresponds to a specified ratio and is determined as the relationship between the weight change per unit time of the container 23A and the weight change per unit time of the container 23B when the current CRP value matches the TV. The weight change per unit time may be determined by operating any conventional differential algorithm on the respective signals S1, S2. Once the WCR is determined, the medical fluid is produced in the main channel 121. Accordingly, in step 1107, the valve arrangement 27A may be operated to close the bypass channel 121 and open the main channel 21 to direct the medical fluid into the receiving device 30'. It should be noted that tuning procedure 1100 may be performed as part of method 200, with steps 1101-1102 being performed in step 201, step 1103 being performed in step 202, and steps 1104-1107 being performed as part of step 204. Following step 1107, control device 40 may continuously control the speed of pumps 25A, 25B such that signals S1, S2 satisfy the WCR, and a medical fluid of the desired composition is produced.

[0098] In a variant, pumps 25A, 25B are stopped after step 1106 and step 1107 may or may not be performed. Method 200 is then performed later using WCR as the specified ratio. At the start of method 200, valve arrangement 27A may be operated to direct liquid to drain 38 via bypass channel 121 until step 204 achieves the specified ratio (WCR). Valve arrangement 27A may then be operated to close bypass channel 121 and direct medical liquid into receiving device 30'. Optionally, medical liquid is directed to receiving device 30' only if the current CRP value provided by signal S3 matches TV.

[0099] The adjustment procedure 1100 of Figure 11 can be extended if the medical fluid is produced by mixing more than two liquids, for example, the three liquids as shown in Figures 5A-5B. For example, steps 1102-1106 can be repeated for another combination of available liquids, resulting in the determination of a second WCR that forms the second ratio described above.

[0100] In the technology proposed herein, two or more components of a medical fluid are provided in appropriate amounts for mixing in the main channel based on measurement signals from scales associated with containers holding the respective components. This eliminates the need for continuous feedback from the CRP sensor to ensure that the medical fluid is produced with the correct composition. In the example of FIG. 10, the CRP sensor 36 is instead placed in the bypass channel 121 and is exposed to the components only during the adjustment procedure 1100. Thereby, the medical fluid does not pass the CRP sensor 36 on its way to the receiving device 30' and is therefore not exposed to microorganisms that may be present in the CRP sensor 36. This alleviates the need for intermittent disinfection of the CRP sensor 36 and the need to intermittently replace the CRP sensor 36. Furthermore, by limiting exposure to the medical fluid, fouling of the CRP sensor 36 is reduced, for example in terms of scaling. Thereby, the operational life of the CRP sensor 36 is extended and it is even possible to use a permanent CRP sensor. Since CRP sensors are generally expensive, significant cost savings are possible.

[0101] For this reason, the CRP sensor 36 may be removably connected to the disposable arrangement of the system 20, so that the CRP sensor 36 is reused while the disposable arrangement is discarded between treatments. In the system of FIG. 10, the disposable arrangement includes a first container 23A, liquid channels 29, 21, 22B, 121. Furthermore, the disposable arrangement includes an inlet connector 21A for connecting to the source 10, an outlet connector 21B for connecting to the receiving device 30', a terminal connector 21C of the bypass channel 121 for connecting to the CRP sensor 36, and an inlet connector 22B' for connecting to the second container 23B. Although not shown in FIG. 10, the disposable arrangement may include engagement portions for engaging with pumps 25A, 25B (see E1, E2 in FIG. 3B).

[0102] In a variation of the system 20 of Figure 10, the CRP sensor 36 is instead located in the main channel 21 upstream of the valve arrangement 27A. The adjustment procedure 1100 of Figure 11 is equally applicable to this variation. However, as will be appreciated from above, the operational life of the CRP sensor 36 may be more limited in this location.

[0103] While the subject matter of the present disclosure has been described in connection with what are presently considered to be the most practical and preferred embodiments, it is to be understood that the subject matter of the present disclosure is not to be limited to the disclosed embodiments, but on the contrary, is intended to cover various modifications and equivalent arrangements that come within the spirit and scope of the equivalents of the appended claims.

[0104] Below, a set of clauses are recited to summarize certain aspects and embodiments of the invention disclosed above.

[0105] C1. A method of producing a medical fluid for use in the treatment of blood by renal replacement therapy, the method comprising: operating (201) a first pump (25A) to pump a first fluid from a first container (23A) disposed on a first scale (24A) through a first fluid channel (21), the first fluid being a component of the medical fluid; and pumping a second fluid from a second container (23B) disposed on a second scale (24B) through a second fluid channel (22B) into the first fluid channel (21) at a junction (26B) of the first fluid channel (21). and operating (202) a second pump (25B) to mix the second liquid in the first liquid channel (21), the second liquid being a constituent of the medical liquid, and controlling (204) the first and second pumps (25A, 25B) based on first and second output signals (S1, S2) from the first and second scales (24A, 24B) to achieve a first ratio between a first flow rate of the first liquid to the junction (26B) and a second flow rate of the second liquid to the junction (26B).

[0106] C2. A method as described in C1, wherein the first and second liquid channels (21, 22B) and the first and second containers (23A, 23B) are combined to form a disposable arrangement (120) that is replaced during the renal replacement therapy or discarded when the renal replacement therapy is completed.

[0107] C3. A method according to C1 or C2, wherein the controlling (204) includes determining a first weight change per unit time of the first scale (24A) and a second weight change per unit time of the second scale (24B) based on the first and second output signals (S1, S2), and operating the first and second pumps (25A, 25B) to achieve the first ratio between the first and second weight changes per unit time.

[0108] C4. A method according to any of the preceding clauses, further comprising detecting (205-206) the need to refill the first container (23A) based on the first output signal (S1) and selectively dispensing (208) the first liquid from a liquid supply source (10) into the first container (23A).

[0109] C5. A method according to any of the preceding clauses, further comprising operating (203) a third pump (25C) to pump a third liquid from a third container (23C) arranged on the second balance (24B) through a third liquid channel (22C) into the first liquid channel (21) at the junction (26B) or a further junction (26C) of the first liquid channel (21) and mix the third liquid in the first liquid channel (21), the third liquid being a constituent of the medical liquid, the third pump (25C) being operated to achieve a second ratio between the second flow rate of the second liquid to the junction (26B) and a third flow rate of the third liquid to the junction (26B) or the further junction (26C).

[0110] C6. A method as described in C5, wherein the third pump (25C) operates to achieve the second ratio by setting the pumping speed of the third pump (25C) in relation to the pumping speed of the second pump (25B) based on known stroke volumes of the second and third pumps (25B, 25C).

[0111] C7. The method according to C5 or C6, further comprising a verification step (600) including: determining an initial resultant value of the second and third flow rates while the second and third pumps (25B, 25C) are operating at their respective initial speeds based on the second output signal (S2) (601); causing a first small change in the pumping speed of one of the second and third pumps (25B, 25C) from its initial speed (602); determining a subsequent resultant value of the second and third flow rates resulting from the first small change based on the second output signal (S2) (603); and evaluating a pumping accuracy of the one of the second and third pumps (25B, 25C) based on the initial resultant value, the subsequent resultant value and the first small change (612).

[0112] C8. The method of C7, wherein evaluating the pumping accuracy (612) comprises: BC,0 -Q BC,1 and comparing the estimated flow value to a set value of the second or third flow rate before the first change; Q BC,0 is the initial composite value, and Q BC,1 is the subsequent synthesis value and α1 is the first small change.

[0113] C9. The method of C8, further comprising: performing (613) a dedicated action if the difference between the estimated flow value and the set point exceeds a limit value.

[0114] C10. A method according to any one of C7 to C9, wherein the verification step (600) includes changing (604) the pumping speed of one of the second and third pumps (25B, 25C) back to the initial speed, determining (605) a further subsequent resultant value of the second and third flow rates resulting from the changing of the pumping speed back to the initial speed based on the second output signal (S2), and comparing (606) the initial resultant value and the further subsequent resultant value.

[0115] C11. The method of C10, wherein the verification procedure (600) further includes performing (608) a dedicated action if a difference between the initial composite value and the further subsequent composite value exceeds a limit value.

[0116] C12. The method according to any one of C7 to C9, wherein the verification step (600) comprises determining (605) a further initial resultant value of the second and third flow rates while the second and third pumps (25B, 25C) are operating at their respective further initial speeds based on the second output signal (S2), and causing (609) a second small change in the pumping speed of the one of the second and third pumps (25B, 25C) from the further initial speed, the second small change being a change in the pumping speed of the pump (25B, 25C) from the further initial speed. and the first small change increases the pumping speed, or vice versa, and determining (610) a further subsequent resultant value of the second and third flow rates resulting from the second small change based on the second output signal (S2), wherein the pumping accuracy of the one of the second and third pumps (25B, 25C) is also evaluated based on the further initial resultant value, the further subsequent resultant value, and the second small change.

[0117] C13. A method according to any one of C7 to C12, wherein the verification step (600) includes modifying (604, 609, 611) the pumping speed of one of the second and third pumps (25B, 25C) for a period of time so as to counteract any increase or decrease in the amount of liquid pumped by the one of the second and third pumps (25B, 25C) resulting from the first slight modification.

[0118] C14. A method according to any of the preceding clauses, comprising the steps of: operating (1101) a valve arrangement (27A; 27', 27'') to open a passage from the first liquid channel (21) to a bypass channel (121) intermediate the junction (26B) and the outlet (21B) of the first liquid channel (21); operating (1102) the first pump (25A) to pump the first liquid from the first container (23A) through the first liquid channel (21) into the bypass channel (121); and operating (1103) the first pump (25A) to pump the second liquid from the second container (23B) through the second liquid channel (22B), the first junction (26B) and the first liquid channel (21) into the bypass channel (121) and discharging the second liquid from the second container (23B) through the second liquid channel (22B), the first junction (26B) and the first liquid channel (21) into the bypass channel (121). operating (1103) the second pump (25B) to provide a mixture of the first and second liquids to a nozzle (121); measuring (1104) the composition-related parameter of the mixture with a sensor (36); adjusting (1105) a pumping speed of at least one of the first and second pumps (25A, 25B) until the sensor (36) measures a target value of the composition-related parameter; and determining (1106) the first ratio as a relationship between a first weight change on the first scale (24A) and a second weight change on the second scale (24B) while the sensor measures the target value based on first and second output signals (S1, S2) from the first and second scales (24A, 24B).

[0119] C15. A method as described in C14, wherein the bypass channel (121) extends to the sensor (36) such that the mixture of the first and second liquids is directed to the sensor (36) by operating the valve arrangement (1101), operating the first pump (1102), and operating the second pump (1103).

[0120] C16. A method according to any one of C1 to C4, further comprising operating (203) a third pump (25C) to pump a third liquid from a third container (23C) arranged on a third scale (24C) through a third liquid channel (22C) into the first liquid channel (21) at the junction (26B) or a further junction (26C) of the first liquid channel (21) and mixing the third liquid in the first liquid channel (21), the third liquid being a constituent of the medical liquid, and the third pump (25C) being controlled to achieve a second ratio between the second flow rate of the second liquid to the junction (26B) and a third flow rate of the third liquid to the junction (26B) or the further junction (26C) based on a third output signal (S3) from the third scale (24C).

[0121] C17. A method according to any of the preceding clauses, further comprising: taking a sample of the medical fluid downstream of the junction (26B) and requesting input of composition data of the sample (204A); and adjusting the first ratio based on the composition data in response to the input of the composition data (204B).

[0122] C18. A method according to any of the preceding clauses, wherein controlling the first and second pumps (204) includes controlling the first flow rate to produce the medical fluid at a flow rate consistent with a consumption rate of the medical fluid in a device for renal replacement therapy (100) connected to receive the medical fluid from the first fluid channel (21).

[0123] C19. A computer-readable medium comprising computer instructions which, when executed by a processor (41), cause said processor (41) to perform a method according to any of the preceding clauses.

[0124] C20. 1. A system for producing a medical fluid for use in the treatment of blood by renal replacement therapy, the system comprising: a first scale (24A); a first container (23A) arranged on the first scale (24A); a first liquid channel (21) arranged to receive a first liquid from the first container (23A); a first pump (25A) arranged to pump a liquid through the first liquid channel (21); a second scale (24B); a second container (23B) arranged on the second scale (24B) and connected to the first liquid channel (21) at a junction (26B) by a second liquid channel (22B); and a second pump arranged to pump a second liquid from the second container (23B) through the second liquid channel (22A) into the first liquid channel (21) and mix the second liquid in the first liquid channel (21), the first and second liquids being components of the medical fluid.

[0125] C21. The system of C20, further comprising a device (264) configured to promote mixing of the second liquid into the first liquid in the first liquid channel (21).

[0126] C22. A system as described in C20 or C21, wherein the first liquid channel (21) further comprises a first end (21A) configured to receive the first liquid from a liquid supply source (10), and the first container (23A) is connected in fluid communication with the first liquid channel (21) between the first end (21A) and the first pump (25A).

[0127] C23. A system described in any one of C20 to C22, wherein the junction (26B) is a three-way connector, the first liquid channel (21) is at least partially defined by tubes (21', 21'') attached to first and second ports (261, 262) of the three-way connector, and the second liquid channel (22B) is at least partially defined by a tube (22') attached to a third port (263) of the three-way connector.

[0128] C24. A system described in any one of C20 to C23, wherein the first and second liquid channels (21, 22B) and the first and second containers (23A, 23B) are combined to form a disposable arrangement (120).

[0129] C25. A system according to any one of C20 to C24, further comprising a bypass channel (121) connected to the first liquid channel (21) intermediate the junction (26B) and an outlet (21B) for the medical fluid, and a valve arrangement (27', 27'') operable to selectively direct liquid to one of the first liquid channel (21) or the bypass channel (121).

[0130] C26. The system of C25, further comprising a sensor (36) configured to measure a composition-related parameter, the bypass channel (121) extending to the sensor (36).

[0131] C27. A system according to any one of C20 to C26, wherein the second pump (25B) is arranged in the second liquid channel (22B) and the first pump (25A) is arranged in the first liquid channel (21) between the junction (26B) and an outlet (21B) for the medical fluid.

[0132] C28. The system according to any one of C20 to C27, further comprising a control device (40) configured to carry out the method according to any one of C1 to C18.

[0133] C29. A disposable arrangement for attachment to an apparatus (100), said disposable arrangement comprising a first container (23A) configured to be attached to a first balance (24A) of said apparatus (100), a first liquid channel (21) arranged to receive a first liquid from said first container (23A), and a second liquid channel (22B) connected to a junction (26B) of said first liquid channel (21), said first liquid channel (21) defining a first engagement portion (E1) for engaging with a first pump (25A) of said apparatus (100), and said second liquid channel (22B) connecting said first liquid channel (22B) to a junction (26B) of said first liquid channel (22B). 2B) defines a second engagement portion (E2) for engaging with a second pump (25B) of the device (100) for pumping a second liquid through the second liquid channel (22B) into the first liquid channel (21) so as to mix the second liquid in the first liquid channel (21), the first and second liquids being components of a medical liquid for use in renal replacement therapy blood therapy, the disposable arrangement being operable to produce the medical liquid in the first liquid channel (21) when attached to the device (100).

[0134] C30. A disposable arrangement as described in C29, wherein the first liquid channel (21) further comprises an inlet end (21A) configured to receive the first liquid from a liquid supply source (10), and the first container (23A) is connected in fluid communication with the first liquid channel (21) between the inlet end (21A) and the junction (26B).

[0135] C31. The disposable arrangement according to C29 or C30, wherein the first container (23A) is empty.

[0136] C32. The disposable arrangement according to any one of C29 to C31, wherein the first liquid is water.

[0137] C33. A disposable arrangement according to any one of C29 to C32, further comprising at least one of a second container (23B) fluidly connected to the second liquid channel (22B) or a connector (22B') of the second liquid channel (22B) for attaching the second container (23B), wherein the second container (23B) is configured to be attached to a second scale (24B) of the device (100).

[0138] C34. The disposable arrangement according to C33, wherein the second container (23B) holds the second liquid.

[0139] C35. The disposable arrangement according to C33 or C34, wherein the second liquid is a liquid concentrate.

[0140] C36. The disposable arrangement according to any one of C33 to C35, further comprising a third liquid channel (22C) connected to the junction (26B) or to a further junction (26C) of the first liquid channel (21), the third liquid channel (22C) defining a third engagement portion for engaging with a third pump (25C) of the device (100) for pumping the third liquid through the third liquid channel (22C) into the first liquid channel (21) so as to mix the third liquid in the first liquid channel (21), the third liquid being a component of the medical liquid.

[0141] C37. A disposable arrangement as described in C36, further comprising at least one of a third container (23B) in fluid communication with the third liquid channel (22C) or a connector of the third liquid channel (22C) for attaching the third container (23C), wherein the third container (23C) is configured to be attached to the second scale (24B) or a third scale of the device (100).

[0142] C38. The disposable arrangement according to C37, wherein the third container (23C) holds the third liquid.

[0143] C39. A disposable arrangement according to any one of C29 to C38, further comprising a sampling port (28) in the first liquid channel (21) downstream of the junction (26B), the sampling port (28) configured to provide access to the medical fluid in the first liquid channel (21) for sampling.

[0144] C40. A disposable arrangement according to any one of C29 to C39, further comprising a bypass channel (121) in fluid communication with the first liquid channel (21) intermediate the junction (26B) and an outlet end (21B) for the medical fluid, the bypass channel (121) comprising a connector (21C) for removable attachment to a sensor (36) for measuring a composition-related parameter.

[0145] C41. A disposable arrangement as described in C40, configured to be attached to a valve arrangement (105) of the device (100), the valve arrangement being operable to selectively direct liquid in the first liquid channel (21) to one of the outlet (21B) or the bypass channel (121).

Claims

1. A method for generating a medical fluid for use in the treatment of blood by renal replacement therapy, the method comprising: operating a first pump (25A) to feed a first liquid from a first container (23A) arranged on a first scale (24A) through a first liquid channel (21), the first liquid being a component of the medical fluid; operating a second pump (25B) to feed a second liquid from a second container (23B) arranged on a second scale (24B) through a second liquid channel (22B) into the first liquid channel (21) at a junction (26B) of the first liquid channel (21) and mixing the second liquid in the first liquid channel (21), the second liquid being a component of the medical fluid; controlling the first and second pumps (25A, 25B) based on first and second output signals (S1, S2) from the first and second scales (24A, 24B) to achieve a first ratio between a first flow rate of the first liquid to the junction (26B) and a second flow rate of the second liquid to the junction (26B); A method comprising the above.

2. The method according to claim 1, wherein the first and second liquid channels (21, 22B), and the first and second containers (23A, 23B) are combined to form a disposable arrangement (120) that is replaced during the renal replacement therapy or discarded when the renal replacement therapy is completed.

3. The method according to claim 1, wherein the controlling (204) comprises determining a first weight change per unit time of the first scale (24A) and a second weight change per unit time of the second scale (24B) based on the first and second output signals (S1, S2), and operating the first and second pumps (25A, 25B) to achieve the first ratio between the first and second weight changes per unit time.

4. The method according to claim 1, further comprising detecting a need to replenish the first container (23A) based on the first output signal (S1) (205 - 206), and selectively filling the first container (23A) with the first liquid from a liquid supply source (10) (208).

5. The method according to claim 1, wherein a third liquid is fed from a third container (23C) arranged in the second weighing device (24B) into the first liquid channel (21) through a third liquid channel (22C) at a junction (26B) or a further junction (26C) of the first liquid channel (21), and a third pump (25C) is operated (203) to mix the third liquid in the first liquid channel (21), wherein the third liquid further comprises a component of the medical liquid, and the third pump (25C) operates to achieve a second ratio between the second flow rate of the second liquid to the junction (26B) and the third flow rate of the third liquid to the junction (26B) or the further junction (26C).

6. The method according to claim 5, wherein the third pump (25C) operates to achieve the second ratio by setting the pumping speed of the third pump (25C) in relation to the pumping speed of the second pump (25B) based on the known stroke volumes of the second and third pumps (25B, 25C).

7. The method according to claim 5, wherein the method comprises determining (601) an initial combined value of the second and third flow rates while the second and third pumps (25B, 25C) operate at their respective initial speeds based on the second output signal (S2); causing a slight change from the initial speed in the pumping speed of one of the second and third pumps (25B, 25C) (602); determining (603) a subsequent combined value of the second and third flow rates resulting from the slight change based on the second output signal (S2); evaluating (612) the pumping accuracy of the one of the second and third pumps (25B, 25C) based on the initial combined value, the subsequent combined value, and the slight change; and further comprises a verification procedure (600) including the above steps.

8. The method according to claim 7, wherein evaluating the pumping accuracy (612) comprises calculating an estimated flow rate value as (Q ＢＣ，０ - Q ＢＣ，１ ) / (1 - α1), and comparing the estimated flow rate value with the set value of the second or third flow rate before the first slight change, where Q ＢＣ，０ is the initial composite value, Q ＢＣ，１ is the subsequent composite value, and α1 is the first slight change.

9. The method according to claim 8, further comprising performing a dedicated action (613) when a difference between the estimated flow rate value and the set value exceeds a limit value.

10. The method according to claim 7, wherein the verification procedure (600) comprises changing (604) the pumping speed of said one of said second and third pumps (25B, 25C) back to said initial speed, and determining (605), based on said second output signal (S2), a further subsequent combined value of said second and third flow rates as a result of making said change to return the pumping speed to said initial speed, and comparing (606) said initial combined value with said further subsequent combined value.

11. The method according to claim 10, wherein the verification procedure (600) further comprises performing (608) a dedicated action when the difference between said initial combined value and said further subsequent combined value exceeds a limit value.

12. The method according to claim 7, wherein the verification procedure (600) determining (605), based on said second output signal (S2), a further initial combined value of said second and third flow rates while said second and third pumps (25B, 25C) operate at respective further initial speeds, causing (609) a second slight change in the pumping speed of said one of said second and third pumps (25B, 25C) from its further initial speed, said second slight change increasing the pumping speed and said first slight change decreasing the pumping speed, or vice versa, determining (610), based on said second output signal (S2), a further subsequent combined value of said second and third flow rates as a result of said second slight change, further comprising evaluating the pumping accuracy of said one of said second and third pumps (25B, 25C) also based on said further initial combined value, said further subsequent combined value and said second slight change.

13. The method according to claim 7, wherein the verification procedure (600) comprises changing (604, 609, 611) the pumping speed of said one of said second and third pumps (25B, 25C) over a certain period so as to cancel out an increase or decrease in the amount of liquid pumped by said one of said second and third pumps (25B, 25C) as a result of said first slight change.

14. The method according to claim 1, wherein Operating the valve arrangement (27A; 27', 27'') (1101) to open a passage from the first liquid channel (21) to the bypass channel (121) intermediate the junction (26B) and the outlet (21B) of the first liquid channel (21), Operating the first pump (25A) (1102) to feed the first liquid from the first container (23A) into the bypass channel (121) via the first liquid channel (21), Operating the second pump (25B) (1103) to feed the second liquid from the second container (23B) through the second liquid channel (22B), the junction (26B) and the first liquid channel (21) into the bypass channel (121) to provide a mixture of the first and second liquids in the bypass channel (121), Measuring a composition-related parameter of the mixture by a sensor (36) (1104), Adjusting the pumping speed of at least one of the first and second pumps (25A, 25B) (1105) until the sensor (36) measures a target value of the composition-related parameter, Determining the first ratio as a relationship between a first weight change of the first scale (24A) and a second weight change of the second scale (24B) while the sensor measures the target value, based on the first and second output signals (S1, S2) from the first and second scales (24A, 24B) (1106), A method, further comprising.

15. The method according to claim 14, wherein the bypass channel (121) extends to the sensor (36) such that the mixture of the first and second liquids is led to the sensor (36) by operating the valve arrangement (1101), operating the first pump (1102), and operating the second pump (1103).

16. The method according to claim 1, wherein a third liquid is fed from a third container (23C) arranged on a third scale (24C) through a third liquid channel (22C) into the first liquid channel (21) at the junction (26B) or a further junction (26C) of the first liquid channel (21), and a third pump (25C) is operated (203) to mix the third liquid in the first liquid channel (21), wherein the third liquid further comprises a component of the medical liquid, and the third pump (25C) is controlled based on a third output signal (S3) from the third scale (24C) to achieve a second ratio between the second flow rate of the second liquid to the junction (26B) and the third flow rate of the third liquid to the junction (26B) or the further junction (26C).

17. The method according to claim 1, further comprising collecting a sample of the medical liquid downstream of the junction (26B), requesting an input of composition data of the sample (204A), and adjusting the first ratio based on the composition data in response to the input of the composition data (204B).

18. The method according to claim 1, wherein controlling the first and second pumps (204) includes controlling the first flow rate to generate the medical liquid at a flow rate that matches the consumption rate of the medical liquid in a device (100) for renal replacement therapy connected to receive the medical liquid from the first liquid channel (21).

19. A computer-readable medium comprising computer instructions that, when executed by a processor (41), cause the processor (41) to execute the method according to any one of claims 1 to 18.

20. A system for generating a medical liquid for use in the treatment of blood by renal replacement therapy, the system comprising a first scale (24A), a first container (23A) arranged on the first scale (24A), a first liquid channel (21) arranged to receive a first liquid from the first container (23A), a first pump (25A) arranged to pump a liquid through the first liquid channel (21), a second scale (24B), A second container (23B) arranged in the second weighing device (24B) and connected to the first liquid channel (21) at a junction (26B) by a second liquid channel (22B), A second pump arranged to feed a second liquid from the second container (23B) into the first liquid channel (21) through the second liquid channel (22A) and to mix the second liquid in the first liquid channel (21), wherein the first and second liquids are components of the medical liquid, and the second pump, A system comprising. **Claim 21** A system according to claim 20, further comprising a device (264) configured to promote mixing of the second liquid into the first liquid in the first liquid channel (21). **Claim 22** A system according to claim 20, wherein the first liquid channel (21) further comprises a first end (21A) configured to receive the first liquid from a liquid supply source (10), and the first container (23A) is fluidly connected to the first liquid channel (21) between the first end (21A) and the first pump (25A). **Claim 23** A system according to claim 20, wherein the junction (26B) is a three-way connector, and the first liquid channel (21) is at least partially defined by tubes (21', 21'') attached to the first and second ports (261, 262) of the three-way connector, and the second liquid channel (22B) is at least partially defined by a tube (22') attached to the third port (263) of the three-way connector. **Claim 24** A system according to claim 20, wherein the first and second liquid channels (21, 22B), and the first and second containers (23A, 23B) are combined to form a disposable arrangement (120). **Claim 25** A system according to claim 20, further comprising a bypass channel (121) connected to the first liquid channel (21) intermediate the junction (26B) and an outlet (21B) for the medical liquid, and a valve arrangement (27A; 27', 27'') operable to selectively direct liquid to one of the outlet (21B) or the bypass channel (121). **Claim 26** The system according to claim 25, further comprising a sensor (36) configured to measure composition-related parameters, wherein the bypass channel (121) extends to the sensor (36).

27. The system according to claim 20, wherein the second pump (25B) is arranged in the second liquid channel (22B), and the first pump (25A) is arranged in the first liquid channel (21) intermediate the junction (26B) and the outlet (21B) for the medical liquid.

28. The system according to any one of claims 20 to 27, further comprising a control device (40) configured to execute the method according to any one of claims 1 to 18.

29. A disposable arrangement for attachment to a device (100), the disposable arrangement comprising a first container (23A) configured to be attached to a first weighing (24A) of the device (100); a first liquid channel (21) arranged to receive a first liquid from the first container (23A); a second liquid channel (22B) connected to a junction (26B) of the first liquid channel (21); comprising the first liquid channel (21) defining a first engagement portion (E1) for engaging a first pump (25A) of the device (100); the second liquid channel (22B) defining a second engagement portion (E2) for engaging a second pump (25B) of the device (100) to feed the second liquid into the first liquid channel (21) through the second liquid channel (22B) so as to mix the second liquid in the first liquid channel (21); the first and second liquids being components of a medical liquid for use in the treatment of blood by renal replacement therapy; the disposable arrangement being attachable to the device (100) and configured to generate the medical liquid in the first liquid channel (21) when in operation. Disposable arrangement.

30. The disposable arrangement according to claim 29, wherein the first liquid channel (21) further comprises an inlet end (21A) configured to receive the first liquid from a liquid supply source (10), and the first container (23A) is fluidly connected to the first liquid channel (21) between the inlet end (21A) and the junction (26B).

31. The disposable arrangement according to claim 29, wherein the first container (23A) is empty.

32. The disposable arrangement according to claim 29, wherein the first liquid is water.

33. The disposable arrangement according to claim 29, further comprising at least one of a second container (23B) in fluid communication with the second liquid channel (22B) or a connector (22B') of the second liquid channel (22B) for attaching the second container (23B), and the second container (23B) is configured to be attached to a second weighing device (24B) of the apparatus (100).

34. The disposable arrangement according to claim 33, wherein the second container (23B) holds the second liquid.

35. The disposable arrangement according to claim 33, wherein the second liquid is a liquid concentrate.

36. The disposable arrangement according to claim 33, further comprising a third liquid channel (22C) connected to the junction (26B) or a further junction (26C) of the first liquid channel (21), the third liquid channel (22C) defining a third engagement portion for engaging a third pump (25C) of the apparatus (100) for pumping the third liquid into the first liquid channel (21) through the third liquid channel (22C) to mix the third liquid in the first liquid channel (21), and the third liquid is a component of the medical liquid.

37. The disposable arrangement according to claim 36, further comprising a third container (23B) in fluid communication with the third liquid channel (22C), or at least one of the connectors of the third liquid channel (22) for attaching the third container (23C), wherein the third container (23C) is configured to be attached to the second weighing means (24B) or the third weighing means of the device (100), the disposable arrangement.

38. The disposable arrangement according to claim 37, wherein the third container (23C) holds the third liquid, the disposable arrangement.

39. The disposable arrangement according to claim 29, further comprising a sampling port (28) in the first liquid channel (21) downstream of the junction (26B), wherein the sampling port (28) is configured to provide access to the medical liquid in the first liquid channel (21) for sampling, the disposable arrangement.

40. The disposable arrangement according to claim 29, further comprising a bypass channel (121) in fluid communication with the first liquid channel (21) intermediate the junction (26B) and the outlet end (21B) for the medical liquid, wherein the bypass channel (121) comprises a connector (21C) for removably attaching to a sensor (36) for measuring composition-related parameters, the disposable arrangement.

41. The disposable arrangement according to claim 40, wherein it is configured to be attached to the valve arrangement (105) of the device (100), and the valve arrangement is operable to selectively direct the liquid in the first liquid channel (21) to one of the outlet end (21B) or the bypass channel (121), the disposable arrangement.

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