Generating medical fluid by mixing base fluid with one or more concentrates

Abstract

A system is operable in a production phase to generate a medical fluid, for example for dialysis, by mixing a base fluid with one or more concentrates by use of volumetric pumps. The system is also operable in a calibration phase (M1) to determine one or more calibration functions that each designates a ratio between the speeds of a pair of volumetric pumps as a function of fluid production rate. In the calibration phase, the speeds of the pair of volumetric pumps are adjusted (S11, S12, S14) to achieve a plurality of fluid production rates of a test fluid, and the calibration function is determined (S15) based on the combinations of speeds that result in the fluid production rates of the test fluid. In the production phase, the production speeds of the volumetric pumps are determined by use of the calibration function(s) and based on a desired fluid production rate of medical fluid.

Description

[0001] GENERATING MEDICAL FLUID BY MIXING BASE FLUID WITH ONE OR MORE CONCENTRATES

[0002] Technical Field

[0003] The present disclosure relates generally to preparation of medical fluid, for example for use in renal replacement therapy, and in particular to preparation of medical fluid by mixing a base fluid with one or more concentrates.

[0004] Background Art

[0005] Renal replacement therapy (RRT) is a therapy that replaces the normal bloodfiltering function of the kidneys. It is used when the kidneys are not working well, which is known as kidney failure and includes acute kidney injury (AKI) and chronic kidney disease (CKD). RRT involves removal of water from the blood of the patient suffering from kidney failure, as well as exchange of solutes with the blood. One example of RRT is peritoneal dialysis (PD), in which a medical fluid is infused into the peritoneal cavity of the patient to interface with the blood of the patient through the peritoneal membrane. Another example of RRT is extracorporeal (EC) blood therapy, in which blood is circulated outside of the patient and interfaced with one or more medical fluids. Modalities of extracorporeal blood therapy include hemodialysis (HD), hemofiltration (HF) and hemodiafiltration (HDF).

[0006] Medical fluids used in HD and PD are commonly known as dialysis fluids. In HF, the medical fluid is known as replacement fluid, since it is infused into the blood of the patient to replace fluid removed during therapy. In HDF, both dialysis fluid and replacement fluid are used.

[0007] RRT is typically automated and performed under control of a dialysis machine. In PD, the machine is known as a cycler, which is connected in fluid communication with the peritoneal cavity and is operated to control the flow of fresh dialysis fluid into the peritoneal cavity and the flow of spent dialysis fluid from the peritoneal cavity. In EC blood therapy, there are two main categories of machines: "chronic machines" for treatment of patient suffering from CKD, and "acute machines" for treatment of patients suffering from AKI.

[0008] Over time, RRT consumes large quantities of medical fluid. It is generally desirable to provide a technique of generating medical fluid for RTT on-demand with accurate composition.

[0009] It is known to prepare medical fluid for RRT by mixing one or more concentrates with a base fluid in the form of purified water. For example, CKD machines have hadthis functionality for several decades. Typically, a conventional system for on-demand generation of medical fluid for RRT comprises a multitude of sensors and advanced control algorithms, which makes the system both complex and costly. Further, many existing systems involve a time-consuming start-up phase, which is performed whenever the system is started and involves pumping water and concentrates to drain while adjusting the pumps to achieve the desired composition and flow rate of the medical fluid. This leads to waste of concentrate.

[0010] In the field of on-demand generation of medical fluid for RRT, it is generally desirable to reduce system complexity, achieve faster start-up, and economize with concentrates. Similar desires are relevant for generation of medical fluid for other uses than RRT.

[0011] Summary

[0012] It is an objective to at least partly overcome one or more limitations of the prior art.

[0013] One objective is to provide a simple and robust technique of generating medical fluid by mixing a base fluid with one or more concentrates.

[0014] Another objective is to provide a such technique that enables fast start-up of a system for generating medical fluid.

[0015] Yet another objective is to provide such a technique that economizes with concentrate.

[0016] One or more of these objectives, as well as further objectives that may appear from the description below, are at least partly achieved by a system for generating a medical fluid, a method of operating a system for generating medical fluid, a computer-readable medium, and a control arrangement according to the independent claims, embodiments thereof being defined by the dependent claims.

[0017] The present disclosure proposes a technique of using volumetric pumps to pump a base fluid and one or more concentrates in a system for generating medical fluid. The technique involves a calibration phase to determine a calibration function for a respective pair of the volumetric pumps, where the calibration function is indicative of how the speeds of the respective pair of volumetric pumps should be varied as a function of the production rate of medical fluid to produce the medical fluid at the production rate and with a desired composition. By the use of volumetric pumps and the calibration function, a system for generating the medical fluid need not be operated by feedback control to continuously adjust the speeds of the pumps. Instead, the system may be operated with fixed speeds of the volumetric pumps, where the speeds are determined by use of the calibration function. Through the use of the calibrationfunction, the speed of the respective volumetric pump is inherently set to compensate for any impact that a change in the production rate of medical fluid may have on the flow rate of the respective volumetric pump. Thus, the proposed technique provides a simple and robust way of generating medical fluid by mixing a base fluid with one or more concentrates. The proposed technique also enables fast start-up of the system, since the speed of the respective volumetric pump is directly given by the calibration function.

[0018] Still other objectives, aspects, embodiments and technical effects, as well as features and advantages may appear from the following detailed description, from the attached claims as well as from the drawings.

[0019] Brief Description of the Drawings

[0020] FIG. 1 is a schematic diagram of an example system that involves generation of treatment fluid for RRT.

[0021] FIG. 2 is a block diagram of an example system for generating treatment fluid. FIG. 3A shows the system of FIG. 2 during generation of treatment fluid, and FIGS 3B-3C shows an example volumetric pump during operation.

[0022] FIG. 4 is a graph of composition error as a function the production rate of treatment fluid.

[0023] FIG. 5 is a flow chart of an example method of performing a calibration phase in a system for generating medical fluid.

[0024] FIG. 6 shows the system of FIG. 2 during a first execution part of the calibration phase.

[0025] FIG. 7 is a graph of an example calibration function determined during a calibration phase.

[0026] FIG. 8 shows the system of FIG. 2 during a second execution part of the calibration phase.

[0027] FIG. 9 is a flow chart of an example method of generating treatment fluid by use of a calibration function.

[0028] FIG. 10 is a flow chart of an example method of performing an evaluation phase in a system for generating treatment fluid.

[0029] FIG. 11 is a graph of an example calibration function before and after an evaluation phase.

[0030] FIG. 12 is a block diagram of an example alternative system for generating treatment fluid.

[0031] Detailed Description of Example EmbodimentsEmbodiments will now be described more fully hereinafter with reference to the accompanying drawings, in which some, but not all, embodiments are shown. Indeed, the subject of the present disclosure may be embodied in many different forms and should not be construed as limited to the embodiments set forth herein; rather, these embodiments are provided so that this disclosure may satisfy applicable legal requirements.

[0032] Also, it will 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. In addition, where possible, any terms expressed in the singular form herein are meant to also include the plural form and / or vice versa, unless explicitly stated otherwise. As used herein, "at least one" shall mean "one or more" and these phrases are intended to be interchangeable. Accordingly, the terms "a" and / or "an" shall mean "at least one" or "one or more", even though the phrase "one or more" or "at least one" is also used herein. As used herein, except where the context requires otherwise owing to express language or necessary implication, the word "comprise" or variations such as "comprises" or "comprising" is used in an inclusive sense, that is, to specify the presence of the stated features but not to preclude the presence or addition of further features in various embodiments.

[0033] As used herein, the terms "multiple", "plural" and "plurality" are intended to imply provision of two or more elements. The term "and / or" includes any and all combinations of one or more of the associated listed elements.

[0034] It will furthermore be understood that although the terms first, second, etc. may be used herein to describe various elements, these elements should not be limited by these terms. These terms are only used to distinguish one element from another. For example, a first element could be termed a second element, and, similarly, a second element could be termed a first element, without departing the scope of the present disclosure.

[0035] Like reference signs refer to like elements throughout.

[0036] Well-known functions or constructions 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.

[0037] As used herein, "dialysis therapy" or "dialysis" refers to any therapy that replaces or supplements the renal function of a patient by use of a treatment fluid. Dialysis therapy includes, without limitation, extracorporeal (EC) blood therapy and peritoneal dialysis (PD) therapy. Dialysis therapy is also denoted renal replacement therapy, RRT, herein.As used herein, "product water" refers to water that has a purity suitable for medical use. In some embodiments, the product water meets criteria of so-called "water for dialysis" "water for injection", or "ultrapure water". For example, criteria for "water for dialysis" or "dialysis water" may be defined in accordance with ANSI / AAMI / ISO 23500-3:2019.

[0038] As used herein, "medical fluid" refers to any fluid that contains one or more substances which are supplied to a patient for a curative, relieving or other medical purpose.

[0039] As used herein, "treatment fluid" refers to a medical fluid that is consumed as a result of dialysis therapy. Treatment fluid includes, without limitation, dialysis fluid for infusion into the peritoneal cavity during PD therapy, dialysis fluid for supply to a dialyzer during EC blood therapy, and replacement fluid and substitution fluid for infusion into blood during EC blood therapy.

[0040] As used herein, a "concentrate" is a substance that contains one or more compounds ("constituents") at a concentration that is higher than at the final use of the substance. A concentrate may be in the form a liquid or a powder. A concentrate is capable of being diluted, if a liquid, or dissolved, if a powder, in a solvent. In the context of the present description, the solvent is water. Before or after being diluted / dissolved in the solvent, the concentrate may be mixed with one or more other concentrates, which also may be in the form of a liquid or a powder.

[0041] FIG. 1 shows an example system 1 which will be used to describe some embodiments. The system 1 comprises a fluid generation system (FGS) 10, which is operable to mix concentrates with a base fluid to produce a medical fluid. In the following, the medical fluid is treatment fluid (TF) for use in renal replacement therapy (RRT). Any number of concentrates may be used. In FIG. 1, the FGS includes two concentrates Cl, C2. The FGS 10 is arranged to receive the base fluid from a source 20 on a supply line 21. The base fluid is or contains product water, PW, that has a purity suitable for medical use. In the examples described herein, it is assumed that the base fluid is product water. In some embodiments, the source 20 is a device that is co-located with the FGS 10 and configured to produce the base fluid on demand. The source 20 may be integrated with the FGS 10 or be a separate machine. In an alternative, the source 20 is a centralized device which is configured to supply the base fluid to a plurality of receivers, for example within a dialysis clinic. In the illustrated example, TF is output by the FGS 10 on a connecting line CL for use by an RRT system 30, which may or may not be part of the system 1, as indicated by dashed lines. The RRT system 30 is configured to perform a conventional RRT treatment by use of TF. RRT systems are well-known to the skilled person and will not be described in further detail.The system 1 further includes a control arrangement or controller 100, which is configured to provide one or more control signals CSi for the FGS 10. By the control signal(s) CSi, the controller 100 causes the FGS 10 to generate the treatment fluid TF with a desired composition and at a desired flow rate. Although not shown in FIG. 1, the controller 100 may be configured to receive one or more output signals of the FGS 10, for example from one or more sensors. An example of an FGS 10 will be described below with reference to FIG. 2.

[0042] The controller 100 may also be configured to provide one or more control signals CSj for the source 20. By the control signal(s) CSj, the controller 100 may cause the source 20 to operate in synchronization with the FGS 10. If the system 1 includes the RRT system 30, the controller 100 may also be configured to provide one or more control signals CSk for the RRT system 30. By the control signal(s) CSk, the controller 100 may cause the RRT system 30 to perform an RRT treatment by use of TF from the FGS 10. The RRT system 30 may be operated to consume TF at a rate that matches the production rate of TF, or to buffer TF. Although not shown in FIG. 1, the controller 100 may be configured to receive one or more output signals of the source 20 and / or the RRT system 30, for example from one or more sensors.

[0043] In the illustrated example, the controller 100 comprises processor circuitry 101 and computer memory 102. A control program may be stored in the memory 102 and executed by the processor circuitry 101 to perform any of the methods, procedures, or functions as described herein. The control program may be supplied to the controller 100 on a computer-readable medium, which may be a tangible (non-transitory) product (e.g., magnetic medium, optical disk, read-only memory, flash memory, etc.) or a propagating signal. In the illustrated example, the controller 100 comprises a signal interface 103a for providing the control signal(s) CSi, and optionally the control signal(s) CSj and / or CSk. The controller 100 may also comprise an input / output (I / O) interface 103b for connection to a user interface (UI) 110. The term "user interface" is intended to include any and all devices that are capable of performing guided humanmachine interaction comprising presentation of information and receipt of input. For example, the UI 110 may comprise a combination of a display device and data entry hardware. The data entry hardware may include one or more of a keyboard, keypad, computer mouse, control buttons, touch panel, microphone and voice control functionality, camera and gesture control functionality, etc. Each of the interfaces 103a, 103b may be configured for wired or wireless data transmission in accordance with any standardized or proprietary protocol. It may be noted that the interfaces 103a, 103b may be implemented by a single interface device.FIG. 2 is a schematic diagram of an example FGS 10 connected to a source 20. In the illustrated example, the FGS comprises a main fluid line or path ("main line") 11 that extends from an inlet 1 la for base fluid to an outlet 1 lb for treatment fluid (TF). The inlet Ila and the outlet 1 lb may comprise terminal connectors for connection to corresponding terminal connectors on other fluid lines. In FIG. 2, the inlet 1 la is connected to a terminal connector 22 on the supply line 21. An on / off valve 12 is arranged in the main line 11 to control the admission of base fluid. A first concentrate supply line 13a extends from a first concentrate inlet 13a' to a first dosing point DPa in the main line 11. A first reservoir Rl, which holds a first concentrate Cl, is releasably connected to the first concentrate inlet 13a'. A first concentrate pump P2a is arranged in the first supply line 13a. A second concentrate supply line 13b extends from a second concentrate inlet 13b' to a second dosing point DPb in the main line 11. A second reservoir R2, which holds a second concentrate C2, is releasably connected to the second concentrate inlet 13b'. A second concentrate pump P2b is arranged in the second concentrate line 13b.The second dosing point DPb is located downstream of the first dosing point DPa.

[0044] Each of the first and second concentrates may comprise any number and types of constituent(s) of the resulting treatment fluid. In some embodiments, when the treatment fluid is produced for use in EC blood therapy, Cl may be an acid concentrate and C2 may be a bicarbonate concentrate, as is well known in the art. In some embodiments, when the treatment fluid is produced for use in PD therapy, Cl may be an electrolyte concentrate and C2 may be a concentrate of an osmotic agent, for example glucose. FIG. 2 is merely an example and the FGS may alternatively be connected to receive a single concentrate or more than two concentrates.

[0045] The FGS includes a mixing arrangement 14, which arranged downstream of the dosing points DPa, DPb and configured to mix the base fluid with the concentrates Cl, C2 to generate TF on the fly. Here, "on the fly" (or "online") implies that TF is generated by continuously mixing the concentrate(s) into the base fluid as the base fluid flows through the FGS. In the illustrated example, the mixing arrangement 14 is a mixing chamber, which is configured to provide the additional function of a bubble trap. A 3-way valve 15 is arranged in the main line 11 downstream of the mixing chamber 14. The valve 15 is connected to a gas removal line 14a, which is connected to a top portion of the mixing chamber 14. The valve 15 is operable to selectively connect the gas removal line 14a to the main line 11, for example to release gas accumulated in the mixing chamber 14 during production of treatment fluid. FIG. 2 is merely an example and the mixing arrangement may include any number of mixing chambers, and / or an inline mixer, an injector mixer, or any other conventional device for mixing liquids.A main pump Pl is arranged in the main line 11 downstream of the valve 15. The main pump Pl sets the flow rate of TF along the main line 11 to the outlet 11b during TF production. Downstream of the main pump Pl, a 3-way valve 17 is arranged in the main line 11 to define a junction to a drain line 18, which extends to a drain 40. The drain 40 may be a fixed installation such as a sink, bathtub, toilet, floor drain, etc.

[0046] Alternatively, the drain 40 may be a reservoir or container for collecting fluid. The 3-way valve 17 is operable to direct the fluid flow along the main line 11 to the outlet 1 lb or from the main line 11 into the drain line 18. It is to be understood that any 3-way valve disclosed herein may be replaced by two or more on / off valves.

[0047] A sensor 16 ("composition sensor") is arranged in the drain line 18 to generate an output signal SI, which represents a composition-related parameter (CRP) of the passing fluid. The CRP may represent conductivity, or equivalently resistivity. In a variant, the CRP represents the concentration of a substance in the treatment fluid, for example bicarbonate or an electrolyte such as sodium, potassium, calcium, magnesium, chloride, etc. If the dialysis fluid is generated for use in PD, the substance may alternatively be an osmotic agent such as glucose. In a further alternative, the CRP may represent the concentration of hydrogen ions, for example in the form of a pH value. In a variant, the sensor 16 is arranged in the main line 11 downstream of the main pump Pl.

[0048] FIG. 3A shows the system of FIG. 2 during TF production. In FIG. 3A, as well as other corresponding drawings herein, open valves and operating fluid pumps are indicated by filled symbols, fluid lines through which fluid is flowing are indicated by thicker lines, and flow directions are indicated by thick solid arrows. The valve 15 is open along the main path 11 and closed towards the gas removal line 14a. The valve 17 is open along the main line 11 and closed towards the drain line 18. The inlet valve 12 is open and the main pump Pl is operated at a first speed ("production speed"). The concentrate pumps P2a, P2b are operated at a respective second speed ("production speed"). By locating the main pump Pl downstream of the dosing points DPa, DPb, the production speed of the main pump Pl defines the production rate of treatment fluid. The flow rate of base fluid into the FGS is given by the difference between the flow rate of the main pump Pl and the sum of the flow rates of the concentrate pumps P2a, P2b. Thus, during production, the speed of the main pump Pl is set to achieve a desired (target) flow rate of treatment fluid, and the production speeds of the pumps P2a, P2b are set to achieve a desired (target) mixing ratio of base fluid and concentrates Cl, C2. The target mixing ratio results in a treatment fluid with desired concentrations of constituents of the concentrate Cl and the concentrate C2. In the following such a constituent is denoted "Cl constituent" and "C2 constituent", respectively. In theexample of PD therapy, the treatment fluid may be generated to have a target concentration of an electrolyte contained in concentrate Cl, and a target concentration of glucose contained in concentrate C2. In the example of EC blood therapy, the treatment fluid may be generated to have a target concentration of an acid contained in concentrate Cl, and a target concentration of bicarbonate contained in concentrate C2.

[0049] In conventional systems for on-line generation of treatment fluid in CKD machines, as mentioned in the Background section, the speeds of the concentrate pumps P2a, P2b are actively and continuously controlled based on a feedback signal indicative of the composition of the treatment fluid, typically from a conductivity sensor in the main line. Examples of such continuous control are disclosed in US 10076735.

[0050] The Applicant has realized that it is possible to dispose with the feedback control and instead operate the pumps Pl, P2a, P2b at fixed speeds during production of treatment fluid. This will enable significant simplification of the operation and configuration of the FGS. It may also improve the robustness of the FGS to disturbances. To remove the feedback control, the operation of the pumps Pl, P2a, P2b needs to be stable over time in terms of the flow rate they generate. This is achieved by using volumetric pumps for the pumps Pl, P2a, P2b.

[0051] As used herein, a "volumetric pump" is a pump that is configured to generate a well-defined flow rate of a fluid by repeatedly discharging a respective stroke volume of the fluid. Volumetric pumps are well-known per se and are also referred to as positive displacement pumps. A volumetric pump is configured to drive a fluid by trapping a fixed and well-defined volume of the fluid in a pump chamber and by forcing (displacing) that trapped volume through a pump outlet by a movable pumping element, e.g., a piston or a diaphragm. Volumetric pumps that may be used in the FGS include reciprocating pumps such as piston pumps, as well as rotary vane pumps and diaphragm pumps. One characteristic of volumetric pumps is that they have a well-defined stroke volume, and that the flow rate of a volumetric pump is controlled via the frequency of the pump, i.e., the frequency of the stroke volumes that are discharged by the pump. In the following, the "speed" of a pump is synonymous with the frequency of stroke volumes.

[0052] In some embodiments, the respective volumetric pump in the FGS comprises a pump chamber and a displacement element, which is arranged for movement in the pump chamber in contact with a fluid to be pumped through the pump chamber.

[0053] Volumetric pumps with such a fluid-contacting displacement element generally have a well-defined and consistent stroke volume.

[0054] FIGS 3B-3C show an example volumetric pump 50 during operation. The pump 50 comprises a housing 51, which defines an internal chamber or cavity ("pumpchamber") 52. A displacement element 53 is arranged for movement in relation to the pump chamber 52 in contact with the fluid to be pumped. The pump chamber 52 comprises one or more inlets 54 (one shown), and one or more outlets 55 (one shown). In FIG. 3B, the displacement element 53 is operated to perform an intake stroke so as to draw fluid into the pump chamber 52 via the inlet(s) 54, as indicated by arrow 54'. In FIG. 3C, the displacement element 53 is operated to perform a pump stroke so as push fluid out of the pump chamber 52 via the outlet(s) 55, as indicated by arrow 55'. It is realized that additional components such as on / off valves may be arranged to control the flow into and out of the pump chamber 52. The operating principle of the pump 50 is applicable to all volumetric pumps with a fluid-contacting displacement element, including but not limited to piston pumps, rotary vane pumps, and diaphragm pumps.

[0055] Since the stroke volume of volumetric pumps is effectively constant, at least in theory, the speeds of the pumps P2a, P2b may be given as a respective ratio ("speed ratio") to the speed of the main pump Pl during TF production. If the TF production rate needs to be changed during production, the speed of the main pump Pl is adjusted to meet the TF production rate, and the speeds of the pumps P2a, P2b are adjusted in accordance with the respective speed ratio. However, the Applicant has found that there is a slight change in composition of the treatment fluid when the TF production rate is changed. After extensive testing, the Applicant has attributed this change in composition to changes in fluid pressure upstream and / or downstream of the respective pump Pl, P2a, P2b, causing changes to the flow rate of respective pump. For example, a change in TF production rate may impact the pressure at the dosing points DPa, DPb as well as the pressure on the inlet side (upstream side) and the outlet side (downstream side) of the main pump Pl. The Applicant has performed tests to quantify the impact of TF production rate on the composition of the treatment fluid. An example result in shown in FIG. 4, which is a graph of composition error as a function of TF production rate ("main flow rate"). During the test, only pumps Pl, P2a were operated, and the main pump Pl was set to provide three different production rates Qp| J = 100 ml / min, QP1,2 = 200 ml / min and Qp | ,3 = 300 ml / min, respectively. For each TF production rate, the speed of the concentrate pump P2a was set in accordance with the speed ratio. As seen from data points 401, 402 in FIG. 4, if the production rate is changed to from 200 ml / min to 100 ml / min, the composition deviates by 1.5% from the expected (desired) composition. Correspondingly, as seen from data points 402, 403, a change in production rate from 200 ml / min to 300 ml / min results in a composition error of 1.2%. The results in FIG. 4 are specific to the FGS that was tested but represent a realistic magnitude of composition errors.To mitigate the composition error, the Applicant has considered determining compensation data in the form of a relation between pressures upstream and downstream of each of the pumps Pl, P2a, P2b and the flow rate generated by the respective pump. During production of treatment fluid, the pressures upstream and downstream of the pumps may be measured, and the speed of the respective pump may be adjusted based on the compensation data to provide a desired flow rate. While such a "brute force" compensation is possible, a simpler approach would be desirable.

[0056] A proposed compensation technique, to be described hereinbelow, is based on the insight that the compensation is rendered simple if calibration data in the form of the speed ratios that yield the desired composition is approximately known for each production rate. Thereby, when the speed of the main pump Pl is set to achieve a TF production rate, the speed of the respective concentrate pump P2a, P2b may be set in relation to the speed of the main pump Pl in accordance with the speed ratios.

[0057] FIG. 5 is a flow chart of an example method Ml that implements a first part of the proposed compensation technique, denoted "calibration phase". The objective of the calibration phase is to determine, for the respective concentrate pump, a calibration function that designates speed ratio as a function of TF production rate. Basically, the method Ml involves generating a test fluid at a plurality of production rates and determining a correct speed ratio for each production rate. The method Ml may be performed by the control arrangement 100 in FIG. 1. The method Ml is performed separately for each combination of the main pump and a concentration pump in the FGS, resulting in a respective calibration function. Thus, in the example of the FGS in FIG. 2, the method Ml is performed separately for pumps Pl, P2a and pumps Pl, P2b. The method Ml will be described for the combination of pumps Pl, P2a. In the FGS of FIG. 2, the valve 17 is operated to direct the fluid flow from the main line 11 into the drain line 18 during the method Ml. Thereby, all test fluid generated by the FGS during the method Ml is discarded instead of being supplied to a receiving device connected to the outlet 1 lb, for example the RRT system 30 (FIG. 1). In a variant, the valve 17 may be omitted and the outlet 1 lb may be disconnected from the receiving device during the method Ml.

[0058] In step S10, which is optional, a calibration composition for use in the method Ml is input, for example by an operator via the UI, by a control function for the RRT system, etc. Step S10 is omitted if the calibration composition is predefined and fixed. The calibration composition corresponds to a concentration of a Cl constituent in the test fluid and is represented by a target value of the signal SI from the sensor 16.

[0059] By steps Sil, S12, S14, an adjustment or tuning procedure is performed to generate a test fluid with the calibration composition at a plurality of calibration flowrates. The test fluid comprises the base fluid and the concentrate Cl. In step SI 1, a calibration flow rate among a plurality of calibration flow rates is selected for use in controlling the FGS. In step S12, the speeds of the pumps Pl, P2a are adjusted or tuned such that the test fluid is generated at the selected calibration flow rate and with the calibration composition. In the FGS of FIG. 2, step S12 may be performed by setting the speed of the main pump Pl to yield the selected calibration flow rate and by then adjusting the speed of the concentrate pump P2a until the signal S 1 meets the target value. The speed of the main pump Pl may be set by open-loop control, or by closed-loop control based on a feedback signal from a flow meter (not shown) in the main line 11 or the drain line 18. In step S13, the combination of speeds that results in the selected calibration flow rate and the calibration composition is determined. The combination of speeds may be stored in memory (cf. 102 in FIG. 1). By step S14, steps S11-S13 are repeated for one or more further calibration flow rates. When steps SI 1-S13 have been performed for all calibration flow rates, the method Ml proceeds to step S15, in which a first calibration function is determined based on the combinations of speeds determined by step S13 for the different calibration flow rates. Specifically, the first calibration function is determined to designate the ratio ("speed ratio") between the speeds of the pumps Pl, P2a as a function of calibration flow rate. In the context of the present disclosure, the term "speed ratio" includes any representation of the relation between the speeds of two pumps. Step S15 may involve storing the first calibration function in memory (cf. 102 in FIG. 1). The first calculation function may be stored as an algorithmic function or as a look-up table.

[0060] The method Ml will be further exemplified with reference to FIGS 6-8. FIG. 6 shows the FGS of FIG. 2 during a calibration phase according to the method Ml. The valve 15 is open along the main path 11 and closed towards the gas removal line 14a. The valve 17 is open towards the drain line 18 and closed towards the outlet 1 lb. The inlet valve 12 is open and the main pump Pl is operated at a first speed that yields the selected calibration flow rate. The concentrate pump P2a is operated at a second speed, whereas the concentrate pump P2b is stopped (non- active). Through the operation of the pumps Pl, P2a, a test fluid is generated in the main line 11 and pumped into the drain line 18. The second speed of the pump P2a is adjusted so that the signal SI from the sensor 16 attains the target value of the calibration composition.

[0061] FIG. 7 is a graph of example data points 701-703 that are derived as a result of the method Ml. In the illustrated example, the method Ml was performed for three different calibration flow rates, resulting in a combination of speeds of the pumps Pl, P2a for each calibration flow rate. In FIG. 7, the abscissa designates calibration flow rate ("main flow rate") and the ordinate designates a ratio of the respective combinationof speeds determined by step S13. In FIG. 7, the speed ratio is given as the quotient between the speed of the concentrate pump P2a and the speed of the main pump Pl. A line CF in FIG. 7 indicates a calibration function that has been determined based on the data points 701-703. In some embodiments, the calibration function is determined, in step S15, by fitting a predefined curve function to the plurality of data points 701-703. Any suitable curve function may be used. For simplicity and processing efficiency, a polynomial function may be fitted to the data points. In the illustrated example, the calibration function CF is a second-order polynomial function that is fitted to the data points 701-703. In a variant, the calibration function may be linear. However, it is currently believed that accuracy is generally improved if the calibration function is a second-order polynomial function. For accuracy, it may be preferable for the method Ml to be performed for at least three different calibration flow rates, so as to result in at least three data points. It may also be preferable for the range of the calibration flow rates to include all production rates that may be used when the FGS is operated to produce of treatment fluid.

[0062] The calibration by method Ml is also performed for the combination of the main pump Pl and the second concentrate pump P2b, to yield a second calibration function. FIG. 8 shows the FGS of FIG. 2 during such a calibration. FIG. 8 differs from FIG. 6 by the first concentrate pump P2a being stopped and the second concentrate pump P2b being operated. Through the operation of the pumps Pl, P2b, a test fluid is generated in the main line 11 and pumped into the drain line 18. The test fluid comprises the base fluid and the concentrate C2. Since the concentrate C2 differs from the concentrate Cl, the composition of the test fluid differs compared to FIG. 8. The pumps Pl, P2b are operated to generate the test fluid with a calibration composition, which corresponds to a concentration of a C2 constituent in the test fluid and is represented by a target value of the signal SI from the sensor 16. Like in FIG. 6, the main pump Pl is operated at a first speed that yields the selected calibration flow rate. The speed of the pump P2b is adjusted so that the signal SI from the sensor 16 attains the target value of the calibration composition. By the method Ml, a second calibration function is obtained for the speed ratio between the pumps Pl, P2b. The calibration flow rates used in FIG. 8 may be the same as used in FIG. 6. It is conceivable that the number of calibration flow rates differs between FIG. 6 and FIG. 8, for example if the accuracy of the individual data points (cf. 701-703 in FIG. 7) is expected to be lower for one concentrate compared to the other concentrate. For example, the accuracy may be lower for a concentrate that yields a smaller response in the signal S 1.

[0063] It is conceivable that one of the concentrates results in no or only weak signal response in the signal SI from the sensor 16. For example, when using a conductivitysensor, glucose is such a small-signal-response (SSR) component. To measure the concentration of the SSR component during the method Ml, the technique described in WO 2024 / 133180 may be used. This means that both of the concentrate pumps P2a, P2b will be operating when the method Ml is performed to determine the calibration function for the concentrate with the SSR component. Assuming that the concentrate C2 contains the SSR component to be measured with the sensor 16, both of the pumps P2a, P2b, as well as the main pump Pl, would be operating in FIG. 8 when the second calibration function is determined.

[0064] FIG. 9 is a flow chart of an example method M2 that implements a second part of the proposed compensation technique, denoted "production phase". The method M2 may be performed by the control arrangement 100 in FIG. 1.

[0065] In step S20, which is optional, a target composition ("production composition") for the treatment fluid to be produced is input, for example by an operator via the UI, by a control function for the RRT system, etc. The target composition may be given as concentrations of the above-mentioned Cl and C2 constituents in the treatment fluid. Step S20 may be omitted if the target composition is given by default and fixed values.

[0066] In step S21, a target flow rate ("production flow rate") of the treatment fluid is obtained. For example, the target flow rate may be entered by an operator via the UI 110 (FIG. 1), or be given by a setting of the RRT system 30 (FIG. 1).

[0067] In step S23, the production speeds of the main pump Pl and the concentrate pumps P2a, P2b are determined, by use of the first and second calibration functions from the calibration phase, to generate the treatment fluid at the target flow rate and with the target composition.

[0068] In step S24, the main pump Pl and the concentrate pumps P2a, P2b are then operated at the respective production speed determined in step S23.

[0069] In the FGS of FIG. 2, a speed ratio between the pumps Pl, P2a that yields a desired concentration of the Cl constituent in the test fluid, can be assumed to also yield the desired concentration of the Cl constituent in the treatment fluid. This assumption is valid as long as the Cl constituent is not contained in the concentrate C2. The basis for this assumption is that in the treatment fluid, compared to the test fluid, some of the base fluid is replaced with the second concentrate C2. If the second concentrate C2 lacks the Cl constituent, the concentration of the Cl constituent is the same in the test fluid and the treatment fluid when generated with the same speed ratio between the pumps Pl, P2a. Correspondingly, a speed ratio between the pumps Pl, P2b that yields a desired concentration of the C2 constituent in the test fluid, can be assumed to yield the desired concentration of the C2 constituent in the treatment fluid, provided that the C2 constituent is not contained in the concentrate Cl.Step S23 is rendered more complex if the concentrate Cl contains the C2 constituent and / or the concentrate C2 contains the Cl constituent. However, the skilled person understands that if the nominal concentrations of the Cl constituent and the C2 constituent in the concentrates Cl, C2 are known, it is possible to determine the speeds of the concentrate pumps P2a, P2b by use of the first and second calibration functions so as to achieve the target composition of the treatment fluid. For simplicity, all examples herein assume that the concentrates Cl, C2 are "non-overlapping", in the sense that the concentrate Cl is free of the C2 constituent and the concentrate C2 is free of the Cl constituent.

[0070] In some embodiments, for example in the FGS of FIG. 2, step S23 comprises setting the production speed of the main pump Pl to yield the target flow rate from step S21, determining a speed ratio for the respective concentrate pump P2a, P2b by use of the target flow rate and the first and second calibration functions, and setting the speed of the respective pump P2a, P2b based on the speed ratio for the respective pump P2a, P2b. This is exemplified in FIG. 7 for a target flow rate Qp| J = 250 ml / min. Given the calibration function CF, a speed ratio Rp2a:Pl = 0.0382 between the pumps P2a and Pl is attained at point 710. Assuming that the calibration function CF has been determined for the target composition of the Cl constituent, the treatment fluid will be generated with the target composition when the speed of the concentrate pump P2a is set to the speed ratio Rp2a:Pl multiplied by the production speed of the main pump Pl.

[0071] It may be noted that it is sufficient to determine the first calibration function for a single calibration composition of the test fluid. The same applies for the second calibration function. If the concentrates Cl, C2 are non-overlapping, a speed ratio obtained for a calibration composition of the test fluid is readily converted into any desired production composition of the treatment fluid by multiplying the speed ratio by a scaling factor, which is equal to the ratio between the production composition and the calibration composition. In a non-limiting example, if the calibration function has been determined for a glucose concentration of 1.36% in the test fluid, and the treatment fluid is to be generated with a glucose concentration of 2.27%, the speed ratio given by the calibration function is multiplied by the scaling factor 1.67 (= 2.27 / 1.36) to yield the desired glucose concentration in the treatment fluid. A corresponding, but more complex, scaling operation may be performed if the concentrates overlap in composition.

[0072] Accordingly, the method M2 may include a step S22 of scaling the respective calibration function based on the calibration composition used in the method Ml and the production composition used in the method M2.During production of treatment fluid in accordance with the method M2, the FGS of FIG. 2 is operated as shown in FIG. 3A. During the start-up of the production phase, it may be beneficial for the valve 17 to be operated to direct the treatment fluid into the drain line 18 until the composition of the treatment fluid has stabilized. The valve 17 is then switched to direct the treatment fluid to the outlet 1 lb. For example, the valve 17 may be switched after a predefined time period, or when the signal S 1 from the sensor 16 is temporally stable. It is also conceivable that the method M2 includes a step of verifying that the temporally stable value is sufficiently close to a target value before the valve 17 is operated to direct the treatment fluid to the outlet 1 lb.

[0073] During the production phase, the FGS may be intermittently operated to release gas accumulated within the mixing chamber 14. To this end, the valve 17 may be operated to direct the fluid flow into the drain line 18. Further, the valve 15 may be operated to direct the fluid flow that enters the mixing chamber 14 into the gas removal line 14a and from the gas removal line 14a back into the main line 11 downstream of the mixing chamber 14, so that the main pump Pl drives the accumulated gas together with treatment fluid into the drain line 18.

[0074] Over time, it may be desirable to update the first and second calibration functions so as to ensure that that treatment fluid is generated with an accurate composition. However, the determination of the first and second calibration functions by the method M2 consumes relatively large amounts of concentrates. The Applicant has realized that it is possible to update the respective calibration function based on a single combination of speed ratio and production rate. This single-point procedure will economize with the concentrates compared to the multi-point procedure that is performed in the calibration phase.

[0075] FIG. 10 is a flowchart of an example method M3 that implements a single-point procedure for evaluating and updating the respective calibration function, denoted "evaluation phase". Like the calibration phase, the evaluation phase involves generating a test fluid by operating the main pump and one of the concentrate pumps P2a, P2b. The method M3 will be described for evaluation of the first calibration function determined for the combination of pumps Pl, P2a, but is equally applicable for evaluation of the second calibration function. Like in the method Ml, the valve 17 may be operated to direct the fluid flow from the main line 11 into the drain line 18 during the method M3.

[0076] As indicated by dashed lines, the method M3 may be initiated by detection of an evaluation trigger. The control arrangement (100 in FIG. 1) may comprise a trigger function that evaluates the operation of the FGS to determine suitable time points for performing the method M3 and generates the evaluation trigger at each such suitable time point. The trigger function may be rule-based or implemented by artificialintelligence. In the following, some non-limiting examples of the trigger function is given. It is to be noted that any of these examples may be used in combination.

[0077] In a first example, the trigger function may be configured to trigger N evaluation phases between each pair of consecutive calibration phases, with N > 1. The value of N may be predetermined, for example based on the robustness of the volumetric pumps and the acceptable waste of concentrates. The value of N may be changed over time, for example based on the total time of operation of the FGS since the pumps were installed, to account for a reduced robustness of the pumps over time. It is currently believed that N > 10 provides a reasonable compromise between reliability and waste of concentrates.

[0078] In a second example, the trigger function may be configured to trigger the evaluation phase based on the signal SI from the sensor 16. If the sensor 16 is arranged in the main line 11, the trigger function may continuously or intermittently monitor the signal SI during TF production for detection of a deviation from a target value. Upon detection of such a deviation, the trigger function may trigger the evaluation phase. If the sensor 16 is arranged in the drain line 18, as in FIG. 2, the valve 17 may be intermittently switched to direct the treatment fluid through the sensor 16 during TF production.

[0079] In a third example, the trigger function may be configured to trigger the evaluation phase as a function of the timing of one or more preceding evaluation phases. For example, the evaluation phases may be performed at a regular time interval by default. If evaluation phases are increasingly being triggered by other causes, for example based on the signal SI, the trigger function may decrease the regular time interval.

[0080] In a fourth example, the trigger function may be configured to trigger the evaluation phase whenever one of the reservoirs Rl, R2 (FIG. 2) are replaced. The control arrangement 100 may monitor the amount of concentrate in the respective reservoir and signal a need for replacement via the UI 110 (FIG. 1). This signal may prompt the user to disconnect and discard one or both reservoirs Rl, R2 and attach one or more replacements. Even if concentrates are manufactured with a nominal composition, the actual composition may differ between batches. The actual composition affects the calibration function. Thus, it may be desirable for the trigger function to trigger the evaluation phase upon replacement of a reservoir.

[0081] The foregoing presumes that the new reservoir contains the same concentrate as the discarded reservoir. Should the new reservoir contain a different concentrate, the control arrangement may be configured to perform the method Ml to determine the calibration function(s) anew. In this context, "different concentrate" implies that thenominal concentration of at least one constituent differs from the concentrate in the discarded reservoir.

[0082] Reverting to FIG. 10, the method M3 may comprise a step S31, in which a target composition ("selected composition") for the test fluid to be produced is input, for example by an operator via the UI, by a control function for the RRT system, etc. The selected composition may be given as a concentration of the Cl constituent in the test fluid. Step S31 may be omitted if the target composition is a default and fixed value.

[0083] In step S32, a target flow rate ("selected flow rate") of the test fluid is obtained. For example, the selected flow rate may be selected based on the calibration flow rates that were used for determining the calibration function in the latest calibration phase. For example, the selected flow rate may be set equal to one of these calibration flow rates and / or be set to a value between the smallest and largest calibration flow rates that were used for determining the calibration function in the latest calibration phase.

[0084] Steps S33 and S34 correspond to steps S12 and S13 in the method Ml. In step S33, the speeds of the main pump Pl and the concentrate pump P2a are adjusted to achieve the selected flow rate of the test fluid with a selected composition at the sensor 16. In step S34, the combination of speeds ("current speeds") that result in the selected flow rate and the selected composition is determined. Like in the method Ml, the combination of speeds may be expressed as a speed ratio between the speeds of the pumps Pl, P2a.

[0085] In step S35, the first calibration function is adjusted based on the combination of speeds from step S34. In some embodiments, step S35 involves shifting the calibration function by an amount given by the combination of speeds.

[0086] FIG. 11 corresponds to FIG. 7 and includes the data points 701-703 used for determining the calibration function CF. The graph in FIG. 11 also includes a data point 702' given by the method M3 for a selected flow rate Qp | ,s = 200 ml / min. To generate the data point 702', a new reservoir R1 with the concentrate Cl was attached to be FGS. In the new reservoir Rl, the concentration of the Cl constituent was 0.25% lower than in the concentrate that was used for determining the calibration function CF. As seen, the data point 702' is shifted from the data point 702 by a speed ratio offset value, RO. In this example, RO is approximately 0.0001, which indeed corresponds to a speed ratio increase of 0.25%. Under the assumption that the shape of the calibration function CF is unaffected, step S35 is performed to shift the calibration function CF vertically to align with the data point 702'. This corresponds to generating the updated calibration function CF' by adding RO to the calibration function CF so that the updated calibration function CF' yields the speed ratio from step S34 for the selected flow rate Qp | ,s- FIG. 11 also shows the use of the updated calibration function CF' during TF production at aproduction rate of Qp I ,s = 250 ml / min. Given the updated calibration function CF', a speed ratio RP2a:Pl = 0.03835 between the pumps P2a and Pl is attained at point 710.

[0087] The controller 100 may be configured to analyze offset values determined by step S35 in consecutive evaluation phases for determining when to perform the next calibration phase. For example, the control arrangement may store the respective offset value and evaluate the trend of the offset values from a series of consecutive evaluation phases to identify a need for a calibration phase. For example, if plural evaluation phases are performed without change of reservoir, a calibration phase may be performed if the offset value or an accumulated offset value for the evaluation phases exceeds a predefined limit.

[0088] It is also conceivable that the next calibration phase is scheduled as a function of the timing of one or more preceding calibration phases. For example, the calibration phases may be performed at a regular time interval by default. If calibration phases are increasingly being triggered by other causes, for example based on the offset values, the regular time interval may be decreased.

[0089] As noted above, a calibration phase may also be performed whenever a reservoir with a different concentrate is installed in the FGS for use in production of treatment fluid.

[0090] FIG. 12 shows an alternative FGS 10 during production of treatment fluid.

[0091] Compared to the FGS in FIG. 2, the main pump Pl is arranged in the main line 11 upstream of the dosing points DPa, DPb. It is to be understood that the compensation technique described hereinabove is equally applicable to the FGS in FIG. 12. In contrast to the FGS in FIG. 2, the production rate of treatment fluid and test fluid is not independently defined by the main pump Pl in the FGS of FIG. 12. It is thus necessary to jointly modify the speeds of plural pumps during steps S12, S22 and S33. This increases the complexity of the proposed compensation technique.

[0092] In the foregoing description, the calibration function designates speed ratio as a function of the production rate of treatment fluid or test fluid. The skilled person understands that the speed ratio between two pumps is equivalent to a ratio of nominal flow rates of the two pumps. A nominal flow rate for a pump is given by multiplying the speed of the pump with the nominal ("rated") stroke volume of the pump. Thus, the calibration function may be represented in terms of any ratio or other metric that is indicative of the speed ratio.

[0093] The proposed compensation technique is not only appliable to generation of treatment fluid for use in RRT but may be applied to generate any type of medical fluid that is generated by mixing a base fluid with one or more concentrates. Examples include medical fluids for infusion into the circulatory system of a human or animalindividual. Such medical fluids include IV (intravenous) solutions. Non-limiting examples of IV solutions include sodium chloride solution 0.9 w / v%, glucose 5% w / v solution, Ringer's solution, Hartman's solution, antibiotics, anticancer drugs, etc. The presented technique is likewise applicable to medical fluids for intramuscular or subcutaneous administration.

[0094] The skilled person realizes that the proposed compensation technique may be expanded to any number of concentrates. Thus, the foregoing description is equally applicable to an FGS that is configured to mix a base fluid with more than two concentrates, or to mix a base fluid with a single concentrate.

[0095] While the subject of the present disclosure has been described in connection with what is presently considered to be the most practical embodiments, it is to be understood that the subject 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 included within the scope of the appended claims.

[0096] Further, while operations are depicted in the drawings in a particular order, this should not be understood as requiring that such operations be performed in the particular order shown or in sequential order, or that all illustrated operations be performed, to achieve desirable results.

[0097] In the following, clauses are recited to summarize some aspects and embodiments as disclosed in the foregoing.

[0098] Cl. A system for generating a medical fluid, said system comprising: a main fluid line extending from a first inlet for a base fluid to an outlet for the medical fluid; a first volumetric pump in the main fluid line; a supply line extending from a second inlet for a concentrate to a dosing point in the main fluid line; a second volumetric pump in the supply line for pumping the concentrate into the main fluid line; a mixing arrangement in the main fluid line between the dosing point and the outlet; a sensor, which is arranged for fluid communication with the main fluid line downstream of the mixing arrangement and is configured to measure a composition-related parameter; and a control arrangement, which is operable to perform a calibration phase and a production phase, wherein the calibration phase comprises: adjusting, for a respective calibration flow rate among a plurality of calibration flow rates, speeds of the first and second volumetric pumps to achieve the respective calibration flow rate of a test fluid with a calibration composition at the sensor; determining, for the respective calibration flow rate, a combination of speeds of the first and second volumetric pumps that results in the respective calibration flow rate of the test fluid with the calibration composition; and determining, based on combinations of speeds determined for the plurality of calibration flow rates, a calibration function that is indicative of a ratio between the speeds of thefirst and second volumetric pumps as a function of flow rate of the test fluid, wherein the production phase comprises: obtaining a target flow rate of the medical fluid; determining, by use of the calibration function, a respective production speed of the first and second volumetric pumps to generate the medical fluid at the target flow rate; and operating the first and second volumetric pumps at the respective production speed.

[0099] C2. The system of Cl, further comprising a drain line, which is connected to the main fluid line at a junction between the mixing arrangement and the outlet, and a valve arrangement, which is operable to close the main fluid line downstream of the junction and open the drain line, wherein the control arrangement, in the calibration phase, is configured to operate the valve arrangement to divert the test fluid into the drain line.

[0100] C3. The system of C2, wherein the control arrangement, in the production phase, is configured to operate the valve arrangement to close the drain line so as to direct the medical fluid to the outlet.

[0101] C4. The system of C2 or C3, wherein the sensor is arranged in the drain line. C5. The system of any preceding clause, wherein the first volumetric pump is arranged downstream of the dosing point.

[0102] C6. The system of any preceding clause, wherein the calibration function is a second-order polynomial function.

[0103] C7. The system of any preceding clause, wherein the control arrangement is configured to determine the combination of speeds for at least three different calibration flow rates.

[0104] C8. The system of any preceding clause, wherein the control arrangement is configured to determine the calibration function by fitting a predefined curve function to a plurality of data points given by the combinations of speeds and the plurality of calibration flow rates.

[0105] C9. The system of any preceding clause, wherein the production phase further comprises, before determining the production speeds: obtaining a production composition of the medical fluid, and scaling the calibration function based on the calibration composition and the production composition.

[0106] CIO. The system of any preceding clause, wherein the control arrangement is further operable to perform an evaluation phase, which comprises: adjusting the speeds of the first and second volumetric pumps to achieve a selected flow rate of the test fluid with a selected composition at the sensor; determining a current combination of speeds of the first and second volumetric pumps that results in the selected flow rate of the test fluid with the selected composition; and adjusting the calibration function based on the current combination of speeds.Cl 1. The system of CIO, wherein the current combination yields a current ratio between the speeds of the first and second volumetric pumps, and wherein the control arrangement is configured to adjust the calibration function by adding an offset value to the calibration function so that the calibration function yields the current ratio for the selected flow rate.

[0107] C12. The system of Cl 1, wherein the control arrangement is configured to store the offset value and evaluate, after a sequence of consecutive evaluation phases, a trend in the offset value for detection of a need to perform the calibration phase.

[0108] C13. The system of any one of C10-C12, wherein the control arrangement is configured to repeatedly perform the calibration phase and the evaluation phase such that the evaluation phase is performed a number of times between calibration phases, said number being at least 10.

[0109] C14. The system of any one of C10-C13, wherein the control arrangement is configured to perform the evaluation phase as a function of a timing of one or more preceding evaluation phases.

[0110] C15. The system of any one of C10-C14, wherein the second inlet is configured for releasable connection to a reservoir that holds the concentrate, and wherein the control arrangement is configured to perform the evaluation phase upon disconnection of the reservoir and connection of a new reservoir that holds the concentrate or a different concentrate.

[0111] Cl 6. The system of any preceding clause, wherein the control arrangement is configured to perform the calibration phase as a function of a timing of one or more preceding calibration phases.

[0112] C17. The system of any preceding clause, wherein the test fluid comprises both the base fluid and the concentrate.

[0113] Cl 8. The system of any preceding clause, wherein the calibration composition is the same for all calibration flow rates

[0114] Cl 9. The system of any preceding clause, wherein the production phase is performed to generate the medical fluid at the target flow rate without feedback control of the first and second volumetric pumps.

[0115] C20. The system of any preceding clause, wherein each of the first and second volumetric pumps comprises a pump chamber and a displacement element, which is arranged for movement in the pump chamber in contact with a fluid to be pumped through the pump chamber.

[0116] C21. The system of any preceding clause, wherein each of the first and second volumetric pumps is one of a piston pump, a rotary vane pump, or a diaphragm pump.C22. A computer-implemented method of operating a system for generating a medical fluid, said system comprising a main fluid line, which extends from a first inlet for a base fluid to an outlet for the medical fluid; a first volumetric pump in the main fluid line; a supply line, which extends from a second inlet for a concentrate to a dosing point in the main fluid line; a second volumetric pump in the supply line for pumping the concentrate into the main fluid line; a mixing arrangement in the main fluid line between the dosing point and the outlet; and a sensor arranged to measure a composition-related parameter of a passing fluid, said method comprising a calibration phase and a production phase, wherein the calibration phase comprises: adjusting, for a respective calibration flow rate among a plurality of calibration flow rates, speeds of the first and second volumetric pumps to achieve the respective calibration flow rate of a test fluid with a calibration composition at the sensor; determining, for the respective calibration flow rate, a combination of speeds of the first and second volumetric pumps that results in the respective calibration flow rate of the test fluid with the calibration composition; and determining, based on combinations of speeds determined for the plurality of calibration flow rates, a calibration function that is indicative of a ratio between the speeds of the first and second volumetric pumps as a function of flow rate of the test fluid, wherein the production phase comprises: obtaining a target flow rate of the medical fluid; determining, by use of the calibration function, a respective production speed of the first and second volumetric pumps to generate the medical fluid at the target flow rate; and operating the first and second volumetric pumps at the respective production speed.

[0117] C23. A computer-readable medium comprising instructions which when executed by processor circuitry causes the processor circuitry to perform the method of C22.

[0118] C24. A control arrangement configured to perform the method of C22 for operating a system to generate a medical fluid.

Claims

24CLAIMS1. A system for generating a medical fluid, said system comprising:a main fluid line (11) extending from a first inlet (Ila) for a base fluid to an outlet (11b) for the medical fluid,a first volumetric pump (Pl) in the main fluid line (11),a supply line (13a; 13b) extending from a second inlet (13a'; 13b') for a concentrate to a dosing point (DPa; DPb) in the main fluid line (11),a second volumetric pump (P2a; P2b) in the supply line (13a; 13b) for pumping the concentrate into the main fluid line (11),a mixing arrangement (14) in the main fluid line (11) between the dosing point (DPa; DPb) and the outlet (11b),a sensor (16), which is arranged for fluid communication with the main fluid line (11) downstream of the mixing arrangement (14) and is configured to measure a composition-related parameter, anda control arrangement (100), which is operable to perform a calibration phase and a production phase,wherein the calibration phase comprises:adjusting (SI 1, S 12, S14), for a respective calibration flow rate among a plurality of calibration flow rates, speeds of the first and second volumetric pumps (Pl, P2a; Pl, P2b) to achieve the respective calibration flow rate of a test fluid with a calibration composition at the sensor (16),determining (S13), for the respective calibration flow rate, a combination of speeds of the first and second volumetric pumps (Pl, P2a; Pl, P2b) that results in the respective calibration flow rate of the test fluid with the calibration composition, and determining (S15), based on combinations of speeds determined for the plurality of calibration flow rates, a calibration function that is indicative of a ratio between the speeds of the first and second volumetric pumps (Pl, P2a; Pl, P2b) as a function of flow rate of the test fluid,wherein the production phase comprises:obtaining (S21) a target flow rate of the medical fluid,determining (S23), by use of the calibration function, a respective production speed of the first and second volumetric pumps (Pl, P2a; Pl, P2b) to generate the medical fluid at the target flow rate, andoperating (S24) the first and second volumetric pumps (Pl, P2a; Pl, P2b) at the respective production speed.

2. The system of claim 1, further comprising a drain line (18), which is connected to the main fluid line (11) at a junction between the mixing arrangement (14) and the outlet (11b), and a valve arrangement (17), which is operable to close the main fluid line (1) downstream of the junction and open the drain line (18), wherein the control arrangement (100), in the calibration phase, is configured to operate the valve arrangement (17) to divert the test fluid into the drain line (18).

3. The system of claim 2, wherein the control arrangement (100), in the production phase, is configured to operate the valve arrangement (17) to close the drain line (18) so as to direct the medical fluid to the outlet (11b).

4. The system of claim 2 or 3, wherein the sensor (16) is arranged in the drain line (18).

5. The system of any preceding claim, wherein the first volumetric pump (Pl) is arranged downstream of the dosing point (DPa; DPb).

6. The system of any preceding claim, wherein the calibration function is a second-order polynomial function.

7. The system of any preceding claim, wherein the control arrangement (100) is configured to determine the combination of speeds for at least three different calibration flow rates.

8. The system of any preceding claim, wherein the control arrangement (100) is configured to determine the calibration function by fitting a predefined curve function to a plurality of data points given by the combinations of speeds and the plurality of calibration flow rates.

9. The system of any preceding claim, wherein the production phase further comprises, before determining the production speeds: obtaining (S20) a production composition of the medical fluid, and scaling (S22) the calibration function based on the calibration composition and the production composition.

10. The system of any preceding claim, wherein the control arrangement (100) is further operable to perform an evaluation phase, which comprises:adjusting (S32, S33) the speeds of the first and second volumetric pumps (Pl, P2a; Pl, P2b) to achieve a selected flow rate of the test fluid with a selected composition at the sensor (16),determining (S34) a current combination of speeds of the first and second volumetric pumps (Pl, P2a; Pl, P2b) that results in the selected flow rate of the test fluid with the selected composition, andadjusting (S35) the calibration function based on the current combination of speeds.

11. The system of claim 10, wherein the current combination yields a current ratio between the speeds of the first and second volumetric pumps, and wherein the control arrangement (100) is configured to adjust (S35) the calibration function by adding an offset value to the calibration function so that the calibration function yields the current ratio for the selected flow rate.

12. The system of claim 11, wherein the control arrangement (100) is configured to store the offset value and evaluate, after a sequence of consecutive evaluation phases, a trend in the offset value for detection of a need to perform the calibration phase.

13. The system of any one of claims 10-12, wherein the control arrangement (100) is configured to repeatedly perform the calibration phase and the evaluation phase such that the evaluation phase is performed a number of times between calibration phases, said number being at least 10.

14. The system of any one of claims 10-13, wherein the control arrangement (100) is configured to perform the evaluation phase as a function of a timing of one or more preceding evaluation phases.

15. The system of any one of claims 10-14, wherein the second inlet (13a'; 13b') is configured for releasable connection to a reservoir (Rl; R2) that holds the concentrate, and wherein the control arrangement (100) is configured to perform the evaluation phase upon disconnection of the reservoir (Rl; R2) and connection of a new reservoir (Rl; R2) that holds the concentrate or a different concentrate.

16. The system of any preceding claim, wherein the control arrangement (100) is configured to perform the calibration phase as a function of a timing of one or more preceding calibration phases.2717. The system of any preceding claim, wherein the test fluid comprises both the base fluid and the concentrate.

18. The system of any preceding claim, wherein the calibration composition is the same for all calibration flow rates19. The system of any preceding claim, wherein the production phase is performed to generate the medical fluid at the target flow rate without feedback control of the first and second volumetric pumps (Pl, P2a; Pl, P2b).

20. The system of any preceding claim, wherein each of the first and second volumetric pumps (Pl, P2a; Pl, P2b) comprises a pump chamber (52) and a displacement element (53), which is arranged for movement in the pump chamber (52) in contact with a fluid to be pumped through the pump chamber (52).

21. The system of any preceding claim, wherein each of the first and second volumetric pumps (Pl, P2a; Pl, P2b) is one of a piston pump, a rotary vane pump, or a diaphragm pump.

22. A computer-implemented method of operating a system for generating a medical fluid, said system comprising a main fluid line, which extends from a first inlet for a base fluid to an outlet for the medical fluid; a first volumetric pump in the main fluid line; a supply line, which extends from a second inlet for a concentrate to a dosing point in the main fluid line; a second volumetric pump in the supply line for pumping the concentrate into the main fluid line; a mixing arrangement in the main fluid line between the dosing point and the outlet; and a sensor arranged to measure a composition-related parameter of a passing fluid, said method comprising a calibration phase and a production phase,wherein the calibration phase comprises:adjusting (SI 1, S 12, S14), for a respective calibration flow rate among a plurality of calibration flow rates, speeds of the first and second volumetric pumps to achieve the respective calibration flow rate of a test fluid with a calibration composition at the sensor,determining (S13), for the respective calibration flow rate, a combination of speeds of the first and second volumetric pumps that results in the respective calibration flow rate of the test fluid with the calibration composition, anddetermining (S 15), based on combinations of speeds determined for the plurality of calibration flow rates, a calibration function that is indicative of a ratio between the speeds of the first and second volumetric pumps as a function of flow rate of the test fluid,wherein the production phase comprises:obtaining (S21) a target flow rate of the medical fluid,determining (S23), by use of the calibration function, a respective production speed of the first and second volumetric pumps to generate the medical fluid at the target flow rate, andoperating (S24) the first and second volumetric pumps at the respective production speed.

23. A computer-readable medium comprising instructions which when executed by processor circuitry causes the processor circuitry to perform the method of claim 22.

24. A control arrangement configured to perform the method of claim 22 for operating a system to generate a medical fluid.

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