A method and an apparatus for online generation of a medical fluid with compensation dosing

Abstract

A method for generating a medical fluid in a fluid line comprising an inlet for receiving a base fluid, a supply point for adding a substance, a hold-up volume downstream of the supply point, and an outlet for delivering the medical fluid comprising a mixture of the base fluid and the substance. The method comprises: holding (500) an initial fluid in the fluid line; starting (531) generation of the medical fluid of a target substance concentration based on receiving base fluid in the fluid line while adding the substance at a target rate; adding (532), based on an offset between the target substance concentration and initial substance concentration of the initial fluid, a compensation dosage of the substance into the fluid line; and delivering (550), from the outlet to a receiving entity, the generated medical fluid comprising at least an amount of the initial fluid and of the compensation dosage. An apparatus comprising such a fluid line is further proposed, in which apparatus a control system is configured to execute the method.

Description

[0001] A METHOD AND AN APPARATUS FOR ONLINE GENERATION OF A MEDICAL FLUID WITH COMPENSATION DOSING

[0002] Technical Field

[0003] The present disclosure generally relates to the field of medical fluid generation. The proposed solution may be set out in an apparatus configured for online generation of the medical fluid, during which a continually supplied base fluid is mixed with at least one soluble substance to obtain and subsequently deliver the medical fluid. Specifically, the proposed solution relates to compensation dosing upon changing medical fluid composition to inter alia mitigate substance waste.

[0004] Background

[0005] Fluids which are obtained from mixing a base fluid with at least one substance which is soluble in the base fluid may be generated for various purposes. Notably, mixed fluids in the form of medical fluids may be generated for use in therapeutic treatment of a patient. In various apparatus types, a session of medical fluid generation may be followed by a session of cleansing of fluid systems of the apparatus, e.g., for reasons of functionality of the apparatus or due to regulatory requirements. This may, inter alia, be carried out to ensure that at least one solute is removed from or at least diluted to a reasonable degree in the fluid systems of the apparatus.

[0006] On example of medical fluids generated for use in therapeutic treatment of a patient relates to fluids used in dialysis treatment, which may be required or beneficial when a person’s renal system has failed, such that it is no longer possible to balance water and minerals or to excrete daily metabolic load. Toxic end products of metabolism, such as, urea, creatinine, uric acid and others, may accumulate in a patient’s blood and tissue. Dialysis removes waste, toxins, and excess water from the body that normal functioning kidneys would otherwise remove and is typically applied when kidney function is reduced and, above all, upon kidney failure.

[0007] One type of kidney failure therapy is peritoneal dialysis (“PD”), which infuses a medical fluid known as a dialysis solution, also called dialysis fluid, into a patient’ s peritoneal cavity via a catheter. The dialysis fluid is in contact with the peritoneal membrane in the patient’s peritoneal cavity. Waste, toxins, and excess water pass from the patient’ s bloodstream, through the capillaries in the peritoneal membrane, and into the dialysis fluid due to diffusion and osmosis, i.e., an osmotic gradient occurs across the membrane. An osmotic agent in the PD dialysis fluid provides the osmotic gradient. Used or spent dialysis fluid is drained from the patient, removing waste, toxins, and excess water from the patient. This cycle is repeated, e.g., multiple times, at one therapy occasion. Traditionally, PD fluids are prepared in a factory and shipped to the patient’s home in ready-to-use bags, which may e.g., hold 5 or 8 liters of medical fluid.

[0008] As indicated, dialysis machines, either for hemodialysis or for peritoneal dialysis, usually require a fair amount of fresh dialysis fluid to be used during the respective therapies. Handling a huge number of relatively heavy bags storing ready to use dialysis fluid is sometimes problematic and requires both physical effort and storing capability. This is particularly, but not exclusively, relevant in the case of home dialysis, wherein it is the patient or his / her family members who has to handle the fluid reservoirs.

[0009] As an alternative, various apparatus types have been suggested, which are capable of producing the medical fluid using a base fluid, typically pre-treated water, and substances comprising proper concentrates. In this context, the medical fluid is generated by, inter alia, mixing the concentrates with the base fluid in a fluid system of the apparatus. This may be referred to as online generation and may e.g., be used for generating and delivering the medical fluid to a receiving entity, such as a container, a medical fluid delivery device, or directly to a patient.

[0010] In certain situations, generation of the medical fluid of a certain target composition, which may be defined by a certain substance concentration, may be initiated from a state in which the fluid contained in the fluid system is of another, initial, composition. This may be the case when starting from a flushed state, at which the fluid system typically contains the base fluid, such as water. Another case may be between different generation stages, wherein the fluid system may initially contain a generated medical fluid of an initial composition which is different from the intended target composition. In such scenarios the initial fluid needs to be replaced before starting to deliver the newly generated medical fluid of the target composition. This leads to time consumption before delivery, and substance waste due to draining of fluid from the fluid system before the target composition is obtained. These problems are particularly prominent where obtainment of a target composition at an outlet of the fluid line is further influenced by internal mixing in a hold-up volume in the fluid line.

[0011] Summary

[0012] A general objective is overcome one or more drawbacks associated with the prior art. An aspect of this objective is to provide a solution for proper configuration of an apparatus configured to generate a medical fluid and a method for use in such an apparatus, so as to minimize waste of resources, such as time and substance concentrate.

[0013] 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 method for generating a medical fluid in a fluid line comprising an inlet for receiving a base fluid, a supply point for adding a substance, a hold-up volume downstream of the supply point, and an outlet for delivering the medical fluid comprising a mixture of the base fluid and the substance. The method may start from an initial state in which an initial fluid of an initial composition is held in the fluid line, and the method comprises: pumping received base fluid in the fluid line while adding the substance at a target rate to obtain a target substance concentration in the generated medical fluid; adding, based on an offset between the target substance concentration and an initial substance concentration of the initial composition, a compensation dosage of the substance into the fluid line; and delivering, from the outlet to a receiving entity, the generated medical fluid comprising at least an amount of the initial fluid and of the compensation dosage.

[0014] According to another aspect, these objectives are targeted by an apparatus configured to generate a medical fluid comprising a mixture of a base fluid and a substance, said apparatus comprising: a fluid line extending from an inlet for receiving the base fluid to an outlet for delivering the medical fluid, said fluid line comprising a hold-up volume; a supply arrangement connected at a supply point in the fluid line, upstream of the hold-up volume, to add the substance into the fluid line; and a control system configured to control the apparatus to start generating the medical fluid, wherein the supply arrangement is controlled to add the substance at a target rate for mixing with base fluid received from the inlet to obtain a target substance concentration, wherein the control system is further configured to control the supply arrangement to add, based on an offset between the target substance concentration and an initial substance concentration of an initial fluid held in the fluid line at said start, a compensation dosage of the substance into the fluid line; and wherein the outlet is connected to a receiving entity to deliver the generated medical fluid comprising at least an amount of the initial fluid and of the compensation dosage.

[0015] As a result of the proposed solution, specifically the added compensation dosage, at least a part of the initial fluid held in the fluid line may be reused. This way, the apparatus is not restricted to begin delivery of the medical fluid upon obtaining the target substance concentration at the outlet. Rather, at least a part of the substance added, or already present, in the fluid line before obtaining the target substance concentration is used as a component of the delivered medical fluid. As a technical effect thereof, substance waste is minimized. Moreover, where a predetermined amount of medical fluid is to be generated, the proposed solution will result in shortening of the time to generate that amount.

[0016] According to some embodiments, adding comprises temporarily adding the substance at a compensation rate which is different from the target rate.

[0017] According to some embodiments, adding the compensation dosage is started at a delayed time point after starting generation of the medical fluid of the target substance concentration.

[0018] According to some embodiments, adding the compensation dosage is started upon starting generation of the medical fluid of the target substance concentration.

[0019] According to some embodiments, delivering is carried out until a batch volume of the medical fluid has been fed to the receiving entity.

[0020] According to some embodiments, the method comprises diverting fluid to drain from the fluid line at the outlet at the start of generation of the medical fluid, wherein the delivery to the receiving entity is started upon obtaining a delivery start concentration of the substance at the outlet.

[0021] According to some embodiments, the delivery start concentration is different from the target substance concentration. According to some embodiments, the delivery to the receiving entity is started upon start of adding of the compensation dosage.

[0022] According to some embodiments, the delivery to the receiving entity is started prior to start of adding of the compensation dosage.

[0023] According to some embodiments, the delivery to the receiving entity is started after start of adding of the compensation dosage.

[0024] According to some embodiments, the base fluid is water and the substance comprises a substance component including an electrolyte.

[0025] According to some embodiments, the initial fluid is the base fluid, said initial substance concentration being zero.

[0026] According to some embodiments, the base fluid is water and the substance comprises a substance component including an osmotic agent.

[0027] According to some embodiments, the initial fluid is a mixture of the base fluid and the substance, wherein the initial substance concentration of the substance component is different from the target substance concentration of the substance component.

[0028] According to some embodiments, the compensation dosage is diluted in the holdup volume.

[0029] According to some embodiments, the method comprises determining substance concentration at the outlet by measuring conductivity of the medical fluid.

[0030] According to some embodiments, the method comprises pre-characterizing dynamics of the fluid line by: adding a pulse of the substance at a predetermined rate upon the initial fluid being the base fluid, and determining substance concentration by measuring conductivity at the outlet while pumping in the fluid line; and determining timing and volume of the compensation dosage based on the precharacterized dynamics and said offset.

[0031] Brief Description of the Drawings

[0032] Fig. 1 is a schematic view of a fluid circuit associated with an apparatus for generating a medical fluid in an online generation phase, wherein a base fluid is continually obtained from an inlet and mixed with at least one substance to form the medical fluid which is passed to an outlet.

[0033] Fig. 2 schematically illustrates a control system for use in an apparatus according to various examples of the proposed solution.

[0034] Fig. 3 schematically illustrates an example of a substance supply arrangement, for use in an apparatus according to various examples of the proposed solution.

[0035] Fig. 4 schematically illustrates a filter setup in an apparatus for carrying out the method according to various examples of the proposed solution, wherein the filter setup comprises two ultrafilters with respective filter chambers which define a hold-up volume in the fluid line.

[0036] Fig. 5 is a flow chart showing various steps included in different examples of a method according to the proposed solution.

[0037] Fig. 6 shows diagrams which schematically illustrate an example of conductivity and composition error upstream and downstream of the hold-up volume when flushing water from the fluid line upon starting to generate medical fluid.

[0038] Fig. 7 schematically illustrates an example of a relation between fluid conductivity and dilution ratio upon changing composition in the fluid line.

[0039] Fig. 8 schematically illustrates an example of how dilution error changes based on lapsed time or pumped fluid, upon changing composition in the fluid line.

[0040] Fig. 9A shows a diagram which schematically illustrates an example of how dilution error changes based on lapsed time or pumped fluid, upon changing composition in the fluid line, with addition of a compensation dosage after start of delivery of medical fluid from the apparatus.

[0041] Fig. 9B shows a diagram of an example corresponding to Fig. 9A, but with addition of a compensation dosage upon start of delivery of medical fluid from the apparatus.

[0042] Fig. 9C shows a diagram of an example corresponding to Fig. 9A, but with addition of a compensation dosage prior to start of delivery of medical fluid from the apparatus.

[0043] Fig. 10A shows diagrams which indicate set concentration for generating the medical fluid and resulting concentration at various points in the fluid line resulting from the start of generating the medical fluid. Fig. 10B shows a diagram which indicates concentration error obtained in a produced batch volume, for an example in which delivery of the medical fluid is started when the obtained substance concentration is very close to the target substance concentration.

[0044] Fig. IOC shows diagrams corresponding to those of Fig. 10B, for an example in which delivery of the medical fluid is started at a lower obtained substance concentration.

[0045] Fig. 11A shows diagrams which indicate set concentration for generating the medical fluid and resulting concentration at various points in the fluid line resulting from the start of generating the medical fluid, wherein a compensation dosage is further added.

[0046] Fig. 1 IB shows a diagram which indicates concentration error in a produced batch volume, with start of delivery of the medical fluid at the same substance concentration as in the example of Fig. IOC, obtained further using the added compensation dosage according to the example of Fig. 11 A.

[0047] Fig. 12A shows diagrams which indicate set concentration for generating the medical fluid and resulting concentration similar to the example of Fig. 11 A, with increased addition of the compensation dosage.

[0048] Fig. 12B shows a diagram which indicates concentration error in a produced batch volume corresponding to the example of Fig. 1 IB, obtained further using the added compensation dosage according to the example of Fig. 12A.

[0049] Fig. 13A shows diagrams which indicate set concentration for generating the medical fluid and resulting concentration similar to the example of Fig. 11 A, in an example where the substance concentration is changed from a first level to a second level.

[0050] Fig. 13B shows a diagram which indicates concentration error in a produced batch volume according to the example of Fig. 13 A.

[0051] Fig. 14A shows diagrams which indicate set concentration for generating the medical fluid and resulting concentration similar to the examples of Figs 11 A and 12A, with substance addition by compensation dosage.

[0052] Fig. 14B shows a diagram which indicates concentration error in a produced batch volume according to the example of Fig. 14A. Detailed Description

[0053] Embodiments will be described more fully hereinafter with reference to the accompanying drawings, in which some 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.

[0054] 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.

[0055] 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.

[0056] 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.

[0057] For brevity and / or clarity, well-known functions or constructions may not be described in detail. 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. The present disclosure generally relates to generation of a medical fluid by continually mixing a base fluid with at least one soluble substance, and to an apparatus configured to carry out such a method. The proposed solution is associated with technical solutions applied upon changing the composition of the fluid held in the apparatus. Specifically, various aspects of the proposed solution will be described herein with references to a method set out in an apparatus configured to generate a medical fluid usable in dialysis treatment.

[0058] For context, it may be noted that different medical fluids may be used depending on the type of dialysis treatment. As already noted, one type of dialysis treatment is peritoneal dialysis (PD) therapy, wherein diffusion through a patient’ s own peritoneal membrane is used for removing waste products from the patient’ s blood.

[0059] Another type of kidney failure therapy is Hemodialysis (“HD”), which in general uses diffusion through a dialyzer membrane to remove waste products from a patient’ s blood. A diffusive gradient occurs along the semi-permeable dialyzer between the blood and a medical fluid often referred to as an HD fluid, which comprises an electrolyte solution called dialysate or dialysis fluid to cause diffusion. HD fluids are typically created by a dialysis machine by mixing concentrates and clean water.

[0060] Hemofiltration (“HF”) is an alternative renal replacement therapy that relies on convective transport of toxins from the patient’ s blood. HF is accomplished by adding a medical fluid, referred to as substitution or replacement fluid, to the extracorporeal circuit during treatment. The substitution fluid and the fluid accumulated by the patient in between treatments is ultrafiltered over the course of the HF treatment, providing a convective transport mechanism that is particularly beneficial in removing middle and large molecules.

[0061] Hemodiafiltration (“HDF”) is a treatment modality that combines convective and diffusive transport mechanisms. HDF let dialysis fluid flow through a dialyzer, as in standard hemodialysis, to provide diffusive clearance. In addition, substitution fluid is delivered directly to the extracorporeal circuit. Therefore, more fluid than the patient’ s excess fluid needs to be removed from the patient, causing an increased convective transport of waste products from the patient

[0062] As used herein, dialysis refers to any therapy / treatment that replaces or supplements the renal function of a patient by use of a medical fluid. Dialysis includes, without limitation, extracorporeal (EC) blood therapy and PD therapy. Various aspects of the present disclosure relate to apparatuses for online preparation of medical fluid such as dialysis fluid for peritoneal dialysis or hemodialysis. In a specific aspect, the present disclosure relates to online preparation of PD fluid to be delivered to a receiving entity, e.g., a cycler for peritoneal dialysis treatments. While the present disclosure focuses more on apparatuses for PD fluid generation, the teachings discussed herein is also applicable to other treatment and injectable fluids, such as continuous renal replacement treatment (“CRRT”) fluids including HD fluids, substitution or replacement fluids for HF and HDF, lactated ringers and the like.

[0063] It may be noted that there are various types of peritoneal dialysis therapies, including continuous ambulatory peritoneal dialysis (“CAPD”), automated peritoneal dialysis (“APD”), tidal flow peritoneal dialysis, and continuous flow peritoneal dialysis (“CFPD”). CAPD is a manual dialysis treatment, where fluid transport is driven by gravity. If initially full of used dialysis fluid, the patient manually connects an implanted catheter to a drain to allow the used or spent dialysis fluid to drain from the patient’s peritoneal cavity. The patient then switches fluid communication so that the patient catheter communicates with a bag of fresh dialysis fluid to infuse the fresh dialysis fluid through the catheter and into the patient. The patient subsequently disconnects the (now empty) bag from the catheter and allows the dialysis fluid to dwell within the peritoneal cavity, wherein the transfer of waste, toxins, and excess water takes place. After a dwell period, the patient repeats the manual dialysis procedure, for example, four times per day. If the peritoneal cavity is not initially full of used dialysis fluid, the sequence is instead fill, dwell, and drain. Manual peritoneal dialysis requires a significant amount of time and effort from the patient, leaving ample room for improvement.

[0064] Automated peritoneal dialysis (“APD”) is similar to CAPD in that the dialysis treatment includes drain, fill, and dwell cycles. APD machines, however, perform the cycles automatically, typically while the patient sleeps. APD machines free patients from having to manually perform the treatment cycles and from having to transport supplies during the day. APD machines are fluidly connected to an implanted catheter, to a source or bag of fresh dialysis fluid and to a fluid drain. APD machines pump fresh dialysis fluid from a dialysis fluid source, through the catheter and into the patient’ s peritoneal cavity. APD machines also allow for the dialysis fluid to dwell within the chamber such that the transfer of waste products, toxins, and excess water can take place. The source may include multiple liters of dialysis fluid including several solution bags. APD machines pump used or spent dialysate from the peritoneal cavity, through the catheter, and to the drain. As with the manual process, several drain, fill and dwell cycles occur during dialysis. A “last fill” may occur at the end of the APD treatment. The last fill fluid may remain in the peritoneal cavity of the patient until the start of the next treatment, or it may be manually emptied at some point during the day.

[0065] Shipping of ready-made medical fluid in bags or other containers brings about various drawbacks. For one thing, transportation of a fluid which predominantly comprises water, which normally is available at the location of use of the medical fluid, may cause undue consumption of resources in terms of fuel, which may result in associated pollution. It also brings about a need for handling storage onsite, such as at a patient’s home e.g., in the case of PD treatment, besides the burden of handling the bags, such as changing bags and disposing of the empty bags.

[0066] A solution is thus to prepare the medical fluid at or near the point of use. This may e.g., include configuring an apparatus for generating (producing) PD fluid locally in the patient’s home by mixing substances also referred to herein as PD fluid concentrates (concentrates for short) with purified water. Instead of having to ship the final medical fluid, of an intended composition, only the concentrates need to be supplied to the point of use (e.g., in bags), whereas the pure water needed for mixing is sourced from e.g. a water purification device that purifies tap water. This may be referred to as an apparatus capable of online production of medical fluid.

[0067] Fig. 1 schematically illustrates an example of such an apparatus 10, where at least some of the relevant elements and functions employed in online production of medical fluid are shown. These elements and functions will be broadly described with reference to Fig. 1, whereas certain elements and functions will additionally be described in more detail further below.

[0068] The apparatus 10 has a fluid circuit which comprises a fluid line 11, indicated by the thicker line in the drawing. The fluid circuit, including the fluid line 11, may be defined by hoses, pipes, tubes, ducts, or other hollow conduits which serve to lead fluid (liquid, in particular) in the apparatus 10. The fluid line 11 extends from an inlet 12 for receiving a base fluid to an outlet 13 for delivering a medical fluid to a receiving entity. The inlet 12 thus acts as an interface configured to receive a base fluid from a base fluid source. For this purpose, the inlet 12 may comprise a connector or port for a hose, tube, or the like.

[0069] By way of example, where the base fluid comprises tap water, a water faucet 1 may serve as the base fluid source located at the point of use of the apparatus 10. A water purifier 2 may be arranged between the base fluid source and the inlet 12 to provide purified water. In some examples, the water purifier 2 may be included in the apparatus 10, whereas Fig. 1 shows an embodiment in which the water purifier 2 is a standalone unit, separate from the apparatus 10 and connected to provide purified water to the inlet 12. Purified water may be obtained in the water purifier 2 by distillation, deionization, reverse osmosis, or other suitable processes and that meets the definition of pure water in the relevant Pharmacopeia. For example, the purified water has a purity level as of “water for dialysis”.

[0070] The apparatus 10 comprises various elements and functions for producing or generating medical fluid of a target composition, from the base fluid obtained from the inlet 12. In the context of the proposed solution, the target composition relates to at least a certain concentration of one or more solutes in the base fluid, which solutes are obtained based on one or more supplied substance, whereas the exact nature and definition of the target composition is not crucial. The substance(s) may be dosed in the form of a concentrate which is diluted in the base fluid to provide a solution of the respective substance(s). For this reason, the terms substance and concentrate are interchangeably used herein. In some examples, a composition is defined by a set of concentrations of different solutes. Examples of such solutes include an osmotic agent such as glucose or icodextrin, or a salt such as NaCl. The concentrate is a highly concentrated solute solution intended for dilution. The target composition may be a desired or predetermined composition, for example determined by a prescription.

[0071] The outlet 13 provides an interface configured to deliver generated medical fluid to a receiving entity 3. For this purpose, the outlet 13 may comprise a connector or port for a hose, tube, or the like. In various examples, the receiving entity may comprise a patient, or a cycler configured to further deliver the medical fluid to a patient, or a device for containing the produced medical fluid, such as a medical fluid bag, or an HD machine.

[0072] The apparatus 10 comprises a fluid pump 14, also referred to herein as a main pump 14, configured to pump fluid in the fluid line 11. The main pump 14 is predominately operated to pump fluid forward, or downstream, in the fluid line 11, i.e. from the inlet 12 to the outlet 13, but may in some examples additionally be operated in the opposite direction, so as to pump or drag fluid from the outlet 13. In some examples, the main pump 14 is a volumetric pump. If the main pump 14 is not a volumetric pump, at least one sensor, such as a flow meter, may be added in the fluid line 11 to provide feedback in a control circuit to ensure a desired flow rate. The main pump 14 may be controlled to obtain a certain flow rate in the fluid line.

[0073] The apparatus further comprises a supply arrangement 20, fluidly connected at a supply point 15 to supply at least one substance, or concentrate, into the fluid line 11. The supply arrangement 20 has an inlet connected to receive at least one type of concentrate from a concentrate source 4 connected to the apparatus 10, such as a bag or other container. The concentrate may be received in the supply arrangement 20 in liquid form, as a gel, or other. In other examples, the concentrate may be provided as a powder, pellets, or other solid state form, wherein the concentrate may be dissolved in the base fluid in the supply arrangement 20 before being injected into the fluid line 11. The supply arrangement 20 is further configured to add the concentrate to the base fluid, for the purpose of generating the medical fluid, by injection of the concentrate at the supply point 15. In order to obtain controlled injection of concentrate, the supply arrangement 20 may comprise at least one concentrate pump, configured to add the substance by pumping. In some examples, the concentrate / sub stance may comprise different substance components, which may be individually injected into the fluid line 11. Further aspects and examples related to the supply arrangement 20 are outlined with reference to Fig. 3.

[0074] The apparatus 10 may further comprise a mixer including a mixing chamber 16, which may comprise a passive flow-driven or motorized mechanism for mixing the concentrate with the base fluid. The mixing chamber 16 is arranged for mixing fluids in the fluid line 11, e.g., to obtain proper homogenization of the mixture of the base fluid and the supplied concentrates.

[0075] The apparatus may further comprise at least one filter 18, such as an ultrafilter (UF), which is intended to reduce or remove microbials and endotoxins from the finally mixed medical fluid prior to fluid delivery at the outlet 13. The filter 18 may comprise at least one chamber 180, capable of holding a volume of fluid. The apparatus may further comprise at least one sensor 17, such as a conductivity sensor, configured to measure a property of the fluid flowing in the main line 11, which property is indicative of the composition of the fluid in the fluid line 11. The drawing indicates placement of the conductivity sensor 17 between the mixer 16 and the filter 18, which may be used for controlling concentrate injection by the supply arrangement 20 upon generating the medical fluid. Additionally, or alternatively, the apparatus 10 may comprise a conductivity sensor 171 positioned to sense fluid conductivity in the fluid line 11 between the filter 18 and the outlet 13. Use of the conductivity sensor 171 in a method according to the proposed solution will be described in further detail below.

[0076] The apparatus may further comprise a valve arrangement 19, three valves 191, 192, 193 being indicated in the drawing by way of example. The valve arrangement 19 may be controlled to, inter alia, selectively connect or disconnect fluid communication to the outlet 13, and to selectively purge fluid from the fluid line 11, e.g., to drain 5. In general, each valve of the valve arrangement 19 has an open state allowing fluid passage and a closed state preventing fluid passage. For each of the shown valves 191, 192, 193, a filled valve symbol triangle represents an open valve port, whereas an empty triangle represents a closed valve port.

[0077] By way of example, the drawing indicates a configuration of the valve arrangement 19 which allows fluid in the fluid line 11 to be led to the outlet 13. In this configuration, valve 193 allows fluid passage from the mixer 16 (past the sensor 17) to an input side of the filter 18, whereas the valve 191 allows passage from an output side of the filter 18 (via the sensor 171) to the outlet 13.

[0078] In an alternative configuration of the valve arrangement 19, fluid in the fluid line 11 is led or diverted to drain 5. This may be obtained by configuring the valve 193 to close passage to the filter 18 while opening passage between the mixer 16 (via the sensor 17) and drain 5. Alternatively, diversion to drain may be obtained by the valve 193 being configured as shown (or dispensed with entirely) and controlling the valve 191 to a closed state while controlling the valve 192 to an open state. The function of valves 191-193 may in an alternative arrangement be accomplished by means of a single path selection valve. Any type of valve suitable for the task may be used, such as an on / off valve, a pinch valve, a cassette valve, a proportional valve, etc.

[0079] The apparatus further comprises a control system 30, configured to operate the apparatus 10 in at least an online generation phase. In the drawing, the control system is represented by a control unit. In an online generation phase of medical fluid, the medical fluid may be continuously produced from received base fluid and added concentrates in the fluid line 11 to be continuously delivered at the outlet 13. The medical fluid is thus produced “inline”. The control system 30 controls the supply arrangement 20 to continuously or continually deliver at least one concentrate at the supply point 15 for mixing with the base fluid in the fluid line 11 to form the medical fluid with a target composition to be delivered at the outlet 13. The control system 30 may further be configured to control the main pump 14, optionally the mixer, and the valve arrangement 19, in the process of medical fluid generation. In this process, the control system 30 may further be configured to take input from the sensor 17 and / or 171 and to adapt control of the elements and functions in the apparatus 10 based on said input.

[0080] Fig. 2 schematically illustrates an example of the control system 30. The control system 30 comprises all necessary components, hardware, and software, to interact with, monitor and control all necessary aspects of the apparatus 10 and its use.

[0081] The control system 30 comprises logic circuitry 31 configured to control the apparatus 10. The logic circuitry 31 may include a processing device 32, including one or multiple processors, microprocessors, data processors, co-processors, and / or some other type of component that interprets and / or executes instructions and / or data. Processing device 32 may be implemented as hardware (e.g., a microprocessor, etc.) or a combination of hardware and software (e.g., a system-on-chip (SoC), an applicationspecific integrated circuit (ASIC), etc.). The processing device 32 may be configured to perform one or multiple operations based on an operating system and / or various applications or programs. The logic circuitry 31 may further include memory storage 33, which may include one or multiple memories and / or one or multiple other types of storage mediums. For example, memory storage 33 may include a random access memory (RAM), a dynamic random access memory (DRAM), a cache, a read only memory (ROM), a programmable read only memory (PROM), flash memory, and / or some other type of memory. Memory storage 33 may include a hard disk (e.g., a magnetic disk, an optical disk, a magneto-optic disk, a solid state disk, etc.). The memory storage 33 is configured for holding computer program code, which may be executed by the processing device 32, wherein the logic circuitry 31 is configured to control the apparatus 10 to carry out any of the method steps as provided herein. Software defined by said computer program code may include an application or a program that provides a function and / or a process. The software may include device firmware, an operating system (OS), or a variety of applications that may execute in the processor 32.

[0082] The control system 30 may further comprise an interface 34, configured for communication with various entities in or associated with the apparatus 10. As indicated, this may, inter alia, include communicating with a user interface 36 and taking input from one or more sensors 37, such as conductivity sensors 17 and 171, and possibly additional sensors for sensing pressure, temperature, flow, or other properties of the fluid in the fluid line 11. The interface 34 may further be configured for providing control output to, inter alia, the supply arrangement 30, the main pump 14, the valves of the valve arrangement 19, etc. Additionally, the control system 30 will further comprise an input of electric power (not shown in the drawing). Connectivity between the control system 30 and further entities of or associated with the apparatus 10, as indicated by arrows in the drawing, may comprise electrical and / or electronic connections. Alternatively, connectivity may be accomplished by wireless connection.

[0083] Fig. 3 schematically illustrates an embodiment of the supply arrangement 20, which may be useful in the apparatus 10 for generation of the medical fluid. In this embodiment, the supply arrangement 20 comprises, at least, two subunits 210 and 220.

[0084] A first subunit 210 is configured to supply a first concentrate, or substance component, which may be an electrolyte concentrate (EC) including an electrolyte. For this purpose, the first subunit 210 may comprise a pump 211, connected with an outlet at the supply point 15 to deliver EC to the fluid line 11. The pump 211 has an inlet 212 which is connectable to an EC source, such as a bag comprising liquid EC. The pump 211 is in some embodiments a volumetric pump. The connections typically include fluid lines.

[0085] A second subunit 220 is configured to supply a second concentrate, or second substance component, which may be an Osmotic Agent Concentrate (OAC) including an osmotic agent, such as glucose, icodextrin, or other. For this purpose, the second subunit 220 may comprise a pump 221, connected with an outlet at the supply point 15 to deliver OAC to the fluid line 11. The pump 221 has an inlet 222 which is connectable to an OAC source, such as a bag comprising liquid OAC. In some embodiments, the pump 221 is a volumetric pump. The connections typically include fluid lines. The supply arrangement 20 is in some embodiments configured to independently set delivery flows of EC and OAC, respectively, under control of the control system 30. This may include, at least, controlling an injection flow rate of the subunits 210, 220 to obtain wished concentrations of the first and second concentrates provided into the fluid line. In turn, this may be obtained by configuring ratios between the main flow QM and the respective injection flow QEC and QOAC. A certain EC concentration thus corresponds to a certain flow ratio, or dosing ratio, rEC =QM / QEC, and a certain OAC concentration corresponds to a certain flow / dosing ratio rOAC =QM / QOAC. Controlling injection flow rate may include controlling injection flow rate of one of the subunits 210, 220 while maintaining the other of the subunits 210, 220 at a constant injection flow, such as zero injection. Control of injection flow rate may be based on sensor feedback to the control system 30 from the sensor 17. The concentration of individual concentrates in the generated medical fluid may be controlled, by the control system 30, by selectively varying the respective injection flow rates in relation to the main flow rate of the main pump 14.

[0086] Fig. 4 schematically illustrates an embodiment of a setup of the filter 18 arranged in the fluid line 11. The filter 18 comprises at least one chamber, which will be substantially or completely filled with fluid upon operation of the apparatus 10. Specifically, in online generation of medical fluid of a target composition, the produced medical fluid will fill up and pass through the filter chamber(s), prior to delivery at the outlet 13. The filter 18 may, as such, comprise one or more individual filters, which may be serially arranged in the fluid line 11, as shown. Specifically, Fig. 4 shows an example wherein the filter 18 comprises two successive filters 181, 183 connected in the fluid line 11. The two filters 181, 183 may be differently or substantially identically configured. It should be noted that more than two filters may alternatively be included in the filter 18. In some examples, at least one filter (i.e., the only filter or one or more of a plurality of filters 181, 183) is an ultrafilter, which is intended to reduce any microbial contamination prior to fluid delivery to the external unit 3.

[0087] Using filter 181 as reference by way of example, each filter may comprise a semipermeable membrane separating a filter volume into an inlet chamber and an outlet chamber, which together form a filter chamber 182. An inlet is connected to the main fluid line 11 for receiving fluid in the filter 181, and an outlet is connected to deliver filtered fluid to the main fluid line 11. In this context, it may be noted that the connection between two successive serially connected filters 181, 183, as in Fig. 4, also forms part of the main fluid line 11. The medical fluid entering the filter through the inlet leaves the filter through the outlet after passing through the semipermeable membrane. The function and characteristics of an ultrafilter is, as such, well-known in the field of dialysis, and is therefore not described in further detail herein. However, it may be noted that filter chamber 180 shown in Fig. 1, which may include chambers 182, 184 of Fig. 4, may comprise a considerable hold-up volume of fluid in the apparatus 10, in particular compared to other entities along the fluid line 11.

[0088] According to established vocabulary, as defined in 3.2.10 of ISO 10991:2023(en), internal volume is a maximum total available volume comprised within a fluidic component, device or system under normal atmospheric pressure. In the context of the solutions proposed herein, the internal volume is the maximal total available volume in the lines including any components. Fluid line 11, including the mixer 16 and the filter 18, can be considered to define the internal volume, or system volume, for holding fluid in the apparatus 10.

[0089] Moreover, as defined in 3.2.7 of ISO 10991:2023(en), hold-up volume is a volume of fluid required to fill a device before a flow is observed at the point of interest or the outlet. A hold-up volume is a part of the internal volume of a system. In the context of the solution proposed herein, the hold-up volume is a liquid volume in one or more of the components in the fluid line 11, for example the mixing chamber 16 or the filter chamber 180 of filter 18. Conduits of the fluid line 11 which are comparatively narrow, such as tubes or pipes, will not add to the problem internal mixing to any greater extent, provided that a plug flow can be assumed. When fluid composition is changed, e.g., between medical fluids of different composition or from water to a medical fluid, the present fluid will be substantially pushed out without mixing when plug-flow occurs. However, in components in the main line 11 in which mixing of fluids occur, plug flow cannot be assumed. At least those components may be considered to contribute to the hold-up volume. This may, e.g., include the mixer 16. However, the hold-up volume may in practical scenarios be predominantly defined by the chamber(s) 180 of the filter(s) 18.

[0090] Referring back to Fig. 1, and with reference to the foregoing, a preferred location of the filter 18 may be downstream of the supply point 15 and the mixing chamber 16, in order to remove contaminants and endotoxins from the finally produced medical fluid. Specifically, it is beneficial that the filter 18 is located downstream of the supply point 15, to remove any contaminants originating from the supply arrangement 20, or from a container of the concentrate source 4. However, this configuration, wherein a large hold-up volume 180 (compared to the other components on the fluid line 11) is introduced at a far downstream position, also presents certain challenges. An intended action of the apparatus 10 is to change the composition of the incoming base fluid and deliver as an output a medical fluid that is different from the base fluid. As a hold-up volume 180 (i.e., provided by the filter 18) is introduced between the concentrate input and mixing, and a receiving device 3 (e.g., a PD cycler) which requires the medical fluid, e.g. PD fluid, to be of correct composition for storing or further administration to a patient, the hold-up volume 180 will act as a buffer volume.

[0091] An intended action of apparatus 10 is to be able to deliver the medical fluid of a certain target composition, which may be selectable, e.g., in terms of concentration of one or more substance concentrates. Upon initiating generation of the medical fluid, the fluid line 11 of the apparatus 10 will typically already contain, or hold, an initial fluid. Specifically, the initial fluid may be of a different composition than the intended target composition. In some scenarios, the fluid line may only initially hold the base fluid, such as purified water, which has been used to flush the fluid line 11 after a previous stage of medical fluid generation and optionally a disinfection stage. In other scenarios, the target concentration may be configured to change between two occasions of medical fluid generation, such as from fill to fill in a PD treatment. The initial fluid may thus be a previously generated medical fluid of a previous target composition.

[0092] Upon starting to generate the medical fluid of the target composition, the initial fluid held is successively pushed downstream in the fluid line 11. As the initial fluid is of different composition than the target composition, the initial fluid pushed downstream may be diverted to drain 5. However, on account of the hold-up volume 180 configured in the fluid line 11, predominantly defined by the filter chamber(s), fluid flow in the fluid line 11 cannot be characterized as a plug flow. Rather, the holdup volume will act as a buffering and mixing volume. This means that the composition downstream of the hold-up volume 180 will change gradually rather than abruptly, when newly generated medical fluid is pumped through the hold-up volume 180 to replace the initial fluid. Obtainment of the target composition at the outlet 13 will thus require a flush volume which greatly exceeds the volume defined by the hold-up volume 180 due to internal mixing. Diverting the flush volume to drain 5 thus causes considerable substance waste as well as time consumption for preparing the apparatus for delivery of the medical fluid to the intended receiving entity 3 at the configured target concentration.

[0093] Fig. 5 provides a flowchart of various steps which may be included in different embodiments of the proposed solution. These steps are briefly discussed below, after which more detailed examples associated with those steps will be described. Specifically, it shall be noted that the order of the steps shown in Fig. 5 is one example of the proposed solution, whereas the order may be different in other examples of the proposed solution, as will be explained with reference to the various detailed examples.

[0094] The process may be controlled by control system 30, indicated in and described with reference to Figs 1 and 2. The proposed solution relates to a process for generating the medical fluid in the fluid line 11. The fluid line 11 comprises the inlet 12 for receiving the base fluid, the supply point 15 for adding a substance, the hold-up volume 180 downstream of the supply point, and the outlet 13 for delivering the medical fluid comprising a mixture of the base fluid and the substance. The base fluid may be water, or purified water. The substance may comprise an electrolyte (E), supplied as an electrolyte concentrate (EC) and / or an osmotic agent (OA) supplied as an osmotic agent concentrate (OAC) such as a glucose concentrate (GC).

[0095] Step 500 indicates an initial state of the apparatus 10 upon starting the method according to the proposed solution. At this starting state, the fluid line 11 of the apparatus 10 holds or contains an initial fluid. The initial fluid has an initial composition defined by an initial substance concentration. The initial fluid may originate from a previous operation of the apparatus 10. The initial fluid may thus at least comprise the base fluid, obtained from the inlet 12, and optionally also a certain concentration of the substance injected at the supply point 15.

[0096] In some examples, the initial fluid is the base fluid, such as water, wherein said initial substance concentration is zero. In other examples, the initial fluid is a mixture of the base fluid and the substance, wherein at least the initial substance concentration of the substance component OA is different from the target substance concentration of the OA. The target substance concentration of the OA may be the desired OA concentration in the medical fluid to generate in, and deliver from, the apparatus 10. The target substance concentration of the OA may thus be seen as one parameter of the target composition of the medical fluid to generate and deliver. In this context, another parameter of the target composition may be a target substance concentration of a substance component comprising electrolytes E.

[0097] The initial composition is known, based on the process used to generate that initial composition, such as flushing with water or generating medical fluid with a previous target composition, as exemplified. Moreover, the initial composition is typically homogenous, i.e., the initial substance concentration is uniform throughout the fluid line 11.

[0098] Step 510 indicates the optional step of monitoring conductivity of fluid in the fluid line 11. This may be carried out at one or more sensing points in the fluid line using at least one conductivity sensor, such as sensor 171 and / or sensor 17 at the respective sensing point. The conductivity is indicative of a concentration at the sensing point(s). Monitoring conductivity may comprise starting to detect the conductivity and continuing to detect the conductivity for a period of time after start. The period of time may end when the target conductivity is reached at the outlet 13 or at an end of delivering the generated medical fluid, such as when a predetermined batch volume has been delivered. Monitoring conductivity may comprise detecting the conductivity repeatedly, such as with a certain measurement frequency. The measurement frequency may be in the range of 0.1-100Hz, such as 5-20Hz., e.g. about 10Hz.

[0099] Step 520 indicates the optional step of determining one or more parameters of the compensation dosage to add. It may be noted that in Fig. 5, step 520 is indicated to occur prior to or at start of generation of the medical fluid. This may comprise precharacterizing of the apparatus 10, as will be described further below. However, in the context of step 520, it shall be noted that in some examples various parameters used for determining the compensation dosage may be obtained after start of generation.

[0100] The control system 30 may already at or before start generation of the medical fluid have access to information of various control parameters usable for determining the compensation dosage, such as: initial substance concentration, based on prior use of the apparatus 10 and / or detection 510 of the conductivity; target substance concentration of the medical fluid to deliver; batch volume to deliver having the target substance concentration, at least on average; pump rate of the main pump 14 to be used for generating the medical fluid.

[0101] The control system 30 is thereby configured to determine at least an offset between the target substance concentration and initial substance concentration. The control system 30 may further be configured to determine various parameters related to adding the compensation dosage.

[0102] Determining the compensation dosage may thus comprise determining characteristics of the compensation dosage, such as: dosage volume of the concentrate to add, in addition to the substance added during generation of the medical fluid of the target concentration; start time of adding the compensation dosage, explicitly or with reference to another event, such as start of generating the medical fluid at the target concentration, or start of delivery to the receiving entity; duration of adding the compensation dosage; compensation rate, characterized by injection rate of the substance or the applied ratio rEC or rOAC during addition of the compensation dosage.

[0103] The compensation rate may be different from the target rate usable for generating the target concentration. When the initial fluid is the base fluid, or a previously generated medical fluid (e.g., for a preceding fill) with a lower initial substance concentration than the target substance concentration to deliver, the compensation dosage may have the character of a temporary pulse, during which the compensation rate is higher than the target rate. Detailed examples will mainly be provided related to such a configuration of the compensation dosage. It shall nevertheless be noted that when the initial fluid has a higher initial substance concentration than the target substance concentration to deliver, the compensation dosage may have the character of a temporary recession (or a negative pulse with reference to the target rate, i.e., a negative volume to add), during which the compensation rate is lower than the target rate. This may, e.g., be the case between fills, changing from a higher OA concentration to a lower OA concentration.

[0104] Step 530 generally indicates generation of the medical fluid.

[0105] Step 531, forming part of the general process of step 530, indicates start of generating the medical fluid of the target substance concentration. This includes initiating generation of the medical fluid of the target substance concentration based on receiving base fluid in the fluid line while adding the substance at a target rate. In this context, the control system 30 may configure the main pump 14 to start pumping at a certain main flow rate and configure the supply arrangement 20 to inject the substance at a target rate into the fluid line while base fluid is introduced at the inlet 12. The target rate may be determined based on the main flow rate, so as to generate the target substance concentration. The start of generating the medical fluid may include starting the main pump 14 and the pump 211 and / or 221.

[0106] Step 532, forming part of the general process of step 530, indicates adding the compensation dosage of the substance into the fluid line 11. As noted, the compensation dosage is configured to be added based on the offset between the target substance concentration and initial substance concentration of the initial fluid. This may include configuring one or more of the volume to add, the timing of adding the compensation dosage, and a rate or duration of adding the compensation dosage.

[0107] In this context, it shall be noted that timing of the compensation dosage addition, with reference to start of generating the medical fluid of the target substance concentration, may have different configurations in different embodiments of the proposed solution. Various examples related to the timing will be described further below. In some examples, adding the compensation dosage is started at a delayed time point after starting generation of the medical fluid of the target substance concentration. In other examples, adding the compensation dosage is started upon starting generation of the medical fluid of the target substance concentration. In yet other examples, adding the compensation dosage is started before starting generation of the medical fluid of the target substance concentration according to step 531.

[0108] Step 540 indicates the optional step of diverting fluid to drain 5 from the fluid line 11 at start 531 of generation of the medical fluid. In this context, valve arrangement 19 may be employed to arrange for the fluid line 11 to connect to the drain 5, e.g., via the valve 193 rather than through the filter 18 and onwards to the outlet 13. Diversion to drain 5 may be configured when the pump 14 starts operating to provide a main flow in the fluid line. Start of pumping may in some examples coincide with the start 531 of generating the medical fluid, i.e. adding the substance at the supply point 15 while receiving the base fluid. In other examples, start of pumping may precede the start 531 of generating the medical fluid, such that the main flow only operates to pump the base fluid in the fluid line 11. Step 550 indicates the step of delivering the generated medical fluid from the outlet 13 to the receiving entity 3, wherein the delivered medical fluid comprises at least an amount of the initial fluid and an amount of the compensation dosage. In cases where the fluid line 11 is configured to divert fluid to drain 5, the step of delivering the generated medical fluid may be activated by means of the control system 30 configuring the valve arrangement 19 to terminate diversion to drain 5 and instead lead fluid from the fluid line out through the outlet 13.

[0109] In some examples, the delivery to the receiving entity is started upon obtaining a delivery start concentration of the substance at the outlet. Obtainment of the delivery start concentration may be determined by the control system 30 based on a conductivity measurement by the sensor 171. In other examples, wherein the apparatus 10 has been pre-characterized to determine the effects of internal mixing in the hold-up volume 180, delivery to the receiving entity may be configured to start upon assessing or calculating that the delivery start concentration has been obtained, based on the precharacterization.

[0110] The delivery start concentration may be different from the target substance concentration. In effect, due to the generation 530 of the medical fluid of the target composition, the substance concentration at the outlet will gradually approach the target composition, on account of the initial fluid being replaced. The delivery start concentration may be configured such that delivery to the receiving entity 3 being initiated at that point in time, and further being compensated with the added compensation dosage, provides for a predetermined batch volume of the medical volume being delivered having said target concentration at least on average, e.g., within a certain accuracy limit.

[0111] In some examples, the delivery start concentration is configured, by the control system 30, such that the medical fluid is delivered with an acceptable offset from the target concentration, based on rules or guidelines associated with a dialysis treatment.

[0112] In examples where the initial substance concentration is lower than the target substance concentration, the delivery start concentration is lower than the target substance concentration, while being higher than the initial substance concentration. In examples where the initial substance concentration is higher than the target substance concentration, the delivery start concentration is higher than the target substance concentration, while being lower than the initial substance concentration. In some examples, delivery 550 to the receiving entity 3 is started upon start of adding 532 the compensation dosage. In other examples, delivery 550 to the receiving entity 3 is started after start of adding 532 the compensation dosage. In yet other examples, the delivery 550 to the receiving entity 3 is started prior to start of adding 532 the compensation dosage. These variants will be further exemplified going forward.

[0113] In some examples, delivery 550 to the receiving entity 3 is started after start 531 of generating the medical fluid to obtain the target substance concentration, i.e., being preceded by diverting 540 fluid from the fluid line 11 to drain 5. This may typically be a relevant configuration when there is a large difference between the initial substance concentration and the target substance concentration, e.g., when the initial fluid is the base fluid. In other examples, delivery 550 to the receiving entity 3 is started upon start 531 of generating the medical fluid. This may be a relevant configuration when there is a small difference between the initial substance concentration and the target substance concentration, e.g., when the initial fluid is a medical fluid of a previous target composition, such as for a preceding fill of a PD treatment.

[0114] Going forward, various details and examples related to the proposed solution will be outlined with reference to generation of a medical fluid which is a mixture of water as the base fluid and electrolytes E and glucose G as the substance. The features of those examples may apply to other examples as well.

[0115] Referring back to Fig. 1, it may be noted that the main pump 14 is configured to set the main flow rate in the fluid line, while the concentrate pumps 211, 221 (Fig. 3) of the supply arrangement 20 control dosing of the substance, including E and G. Upon generating the medical fluid, the concentrate pumps 211, 221 are in a first phase controlled with conductivity feedback from a conductivity sensor 17 located downstream the main pump 14 and mixing chamber 16 to achieve a target composition of the mixed PD fluid, wherein the target composition has an associated target substance concentration of E and G, respectively. At this stage, target dosing ratios rEC and rOAC are established for pumps 14, 211, 221. In a second phase, these pumps may thus be controlled to maintain those speed ratios constant during generation of the medical fluid of the target composition. Medical fluid production rate may be changed by controlling the speed of the main pump 14 while maintaining the dosing ratios constant (concentrate pump speeds changed with same factor as main pump 14). Note that the first phase may not necessarily be executed every time the generation of the medical fluid starts; if the dosing ratios have been established with a given set of concentrates, the generation can “kick start” using these dosing ratios and confirm that proper dosing has been established by a conductivity check. The conductivity sensor 171 located downstream of the ultrafilters 18 is used to sense the conductivity of the fluid at the outlet of the apparatus 10 and can thus be used, together with conductivity sensor 17, to sense a composition difference between the fluid before and after the ultrafilters 18 (e.g., resulting from dilution in the fluid initially present in the ultrafilters).

[0116] One example scenario of the proposed solution is that the initial fluid contained in the fluid line 11 is the base fluid, specifically water. Various aspects related to this scenario are discussed going forward.

[0117] In some examples, the entire fluid line 11 including the ultrafilters 18 are filled with water. This may be water remaining after flushing of the apparatus 10 with water, e.g., flushing of the apparatus 10 with water after a disinfection. Replacing the water in the fluid line 11 with generated medical fluid of the target composition requires time, and the accomplishment of the target composition at the outlet is further prolonged due to internal mixing in the hold-up volume defined by the ultrafilters 18. As noted, this further leads to excessive waste of substance. To, this avail, the present method suggests allowing a certain initial dilution error of the medical fluid downstream the ultrafilters 18 at start of delivery and optionally, depending on the magnitude of the initial dilution error and it’ s resulting total batch error, compensating the dilution error by further substance addition.

[0118] To flush the ultrafilters with medical fluid of correct (target) composition, generation of the medical fluid is initiated (531), typically by kick starting the pumps 14, 211, 221 as described. Due to internal mixing of water and generated medical fluid, particularly in the ultrafilters 18 (as opposed to an ideal plug flow of medical fluid replacing the water), the composition downstream of the ultrafilter 18 will gradually converge from water to that of the medical fluid target composition.

[0119] Fig. 6. Schematically illustrates such a flushing sequence. With reference to the upper diagram, conductivity of the fluid upstream of the UF 18 is denoted CondPreUF, and may be detected using the sensor 17, whereas conductivity of the fluid downstream of the UF 18 is denoted CondPostUF, which may be detected using the sensor 171. The sharp rise in CondPreUF indicates the time when the medical fluid which has started to be generated first reaches sensor 17 by plug flow. The upper diagram shows that CondPostUF converges towards CondPreUF over time (or flow). The lower diagram of Fig. 6 shows how dilution error downstream of UF 18 correspondingly converges towards zero.

[0120] Fig. 7. Shows a diagram which shows how conductivity varies dependent on the dilution error. This diagram was generated based on data from dilution tests wherein an electrolyte concentrate with a nominal dilution ratio of 20 was sequentially diluted with water. The dilution error is a measure of a concentration offset for all solutes included in the electrolyte concentrate resulting from extra water addition. The dilution error DilErr may be expressed in percent and can be calculated from a conductivity deviation (DilErr = 100*(CondPostUF - CondPreUF) / CondPreUF). The dilution error is thus proportional to the conductivity deviation, where CondPostUF in turn is dependent on the substance concentration downstream of the UF 18, i.e., at the outlet 13. The dilution ratio on the x-axis of Fig. 7 is directly and inversely proportional to the dilution error DilErr. Although the conductivity is not linearly dependent on the dilution error over a very wide range of dilution error, linear dependency is a very good approximation in the range of interest (e.g. cond range: 10 to 15 mS / cm or DilErr range: -20 to +20%). This is indicated in Fig. 7, which shows that there is a linear relationship between the dilution error DilErr (represented by the dilution ratio) and the conductivity of the medical fluid.

[0121] Fig. 8 illustrates a diagram which shows how the dilution error DilErr downstream of the UF 18 converges toward zero with increasing flush volume (which correlates directly with time for a given constant main flow) and how different initial dilution error limits could be chosen to control the volume of wasted medical fluid.

[0122] The vertical line at 1400 ml shows an example of a limit that may be considered to have negligible effect on the overall fill volume composition error and thus would not need any composition compensation. However, starting to deliver the medical fluid at that limit would mean that a large volume of medical fluid is wasted.

[0123] The vertical line at 700 ml, on the other hand, shows an example of a higher allowed error limit that may be used to decrease the PD fluid waste but that would on the other hand cause a greater overall fill volume composition error that probably would need to be compensated for. It should be noted, though, that any chosen dilution error limit only represents the initial error (upon start of delivery) and since the dilution error is decreasing with the flush volume, the overall composition error of a complete batch volume (e.g., 2500 ml) will be much smaller than the initial error. Configuring start of delivery to the receiving entity 3 at the vertical line at 700 ml indicates that medical fluid delivery starts at an initial dilution error limit of 2.5% in this example, based on the intersection with the curve showing the dilution error..

[0124] The choice of error limit will typically be a trade-off between fluid waste reduction and the anticipated need for, and ability to, accurately compensate for the initially allowed dilution error by means of the compensation dosage. For a sufficiently small error limit, no compensation may be needed. The need for and amount of compensation can be assessed based on the overall batch (or fill) volume composition error which can be calculated based on the accumulated dilution error and the total fill volume. In Fig. 8, the area marked Al is the integrated dilution error and represents a measure of the substance deficit obtained when delivery starts at 700 ml. Al is the area enclosed by vertical line at 700 ml, representing the error limit, the plot line representing the dilution error, and a horizontal zero error line (top). The unit of Al is e.g. seconds *percent or SP.

[0125] In some examples, Al is determined by real-time integration of the dilution error from the time the error reaches the error limit (e.g., 2.5%) to the time when the error is considered small enough and is causing only a negligible impact (e.g., 0.1%).

[0126] In other examples, Al can be assessed based on used error limit (e.g., 2.5%) and known behaviour of the dilution error, based on historical flush dynamics.

[0127] In other words, the integrated dilution error Al as a function of the chosen error limit may be experimentally determined, for instance once, occasionally, or periodically. This function can then be used to assess Al without the need to perform the real-time integration every time a compensation should happen, for example if it’ s desired to start the compensation dosage before a real-time integration can be completed. The historical flush dynamics can mean earlier flushes run using the same ultrafilters 18 (whereas new data may need to be established when the ultrafilters are replaced, whereupon the hold-up volume in the fluid line 11 may change). It can also mean the most recent dilution error history within the current flush (by predicting Al based on e.g. the first and / or higher order time derivatives of the dilution error prior to reaching the error limit). In yet another alternative, historical flush dynamics may have been obtained in a step of pre-characterizing dynamics of the fluid line 11. This may involve adding a pulse of the substance, at the supply point 15, at a predetermined rate upon the initial fluid being the base fluid and determining substance concentration by measuring conductivity at the outlet, e.g., using sensor 171, while pumping in the fluid line. The measured conductivity will form a pulse response which characterizes the dilution effect, primarily caused by the hold-up volume of the UF 18. Based on the pulse response, known behaviour of the dilution error, corresponding to the shape of the dilution error curve exemplified in Fig. 8, may be synthesized. In any of these alternatives, Al can be determined as an assessment made by the control system 30 based on the characterization data and a given initial error limit at start of delivery.

[0128] Based on the substance deficit, a compensation dosage may be determined. To compensate, pump speeds of both pump 211 for E and pump 221 for G need to be scaled up to add the compensation dosage, i.e., substance volumes corresponding to the dilution error. The speed ratio of the substance pumps 211, 221 (a fix value for a certain composition) should be maintained throughout the process of generating the medical fluid 530, the relative (percentage) speed increment of those two pumps 211, 221 will be the same for the compensation dosage, or compensation event.

[0129] As noted, the compensation dosage may be based on an offset between the target substance concentration and initial substance concentration of the initial fluid. The value of Al depends on when delivery is started, which also defines the volume of the initial fluid that is delivered as part of the medical fluid. Al thereby defines the substance error to be balanced by the compensation dosage. The compensation dosage is thus based on an offset between the target substance concentration and initial substance concentration of the initial fluid and the amount, i.e., volume, of the initial fluid that is delivered as part of the medical fluid. Since the integrated dilution error Al is a measure of the substance deficit (or error, since the initial concentration alternatively may be higher than the target substance concentration) calculated at the same main flow rate as during the compensation, Al can be translated into an error compensation amount A2 expressed in the same unit SP. A2 can then be realized by increasing the concentrate pump speeds with a certain percentage until the A2 matches - Al.

[0130] For example, assume Al integrates to -500 SP when starting fluid delivery at an error limit of -2.5%. This can be compensated for by increasing the concentrate pump speeds with some percentage P during a time period T, to achieve A2 equal to -Al (i.e.= +500 SP). This could for example mean increasing the concentrate pump speeds by P=10% for T=50 seconds or by P=50% for T=10 seconds. If the main flow is different during the compensation addition compared to during compared to during the phase when the dilution error was determined, the +500 SP compensation can be achieved by inversed scaling of A2 with the main flow. The compensation dosage may thus be characterized by a time parameter indicative of temporary addition of the substance, e.g., time period T, and an increase parameter indicative of the compensation rate of substance addition in relation to the target rate (for generating the medical fluid with the target substance concentration), e.g., the percentage P. As indicated earlier, it shall be noted that the percentage P may be negative in certain scenarios, i.e., when the initial fluid has higher substance concentration than the target substance concentration.

[0131] In some examples, the compensation dosage can be added after integrated dilution error Al has been measured. The advantage is then that the actual integrated dilution error is known. There is however a risk that if the compensation is added too late, such that the full compensation dosage will not have time to be fully transported through the fluid line 11 (specifically the ultrafilters 18) and hence not be delivered to the receiving entity before the fill phase ends, e.g., that a predetermined batch volume has been delivered. The added compensation dosage would in that case not fully compensate for the dilution error. Another problem an incomplete passage of the compensation dosage may cause is that medical fluid with higher concentration than intended for the next fill may be present in the ultrafilters 18. This would require at least a minor flush of the ultrafilters 18 before fluid delivery for the next fill can be started.

[0132] To decrease the risk of incomplete compensation dosage delivery, the compensation dosage can start being added before the actual integrated dilution error has been measured, based on assessing the substance deficit Al and hence the corresponding error compensation amount A2 beforehand, as described above. The compensation dosage should however not be added too early since it may then have time to be transported through the ultrafilters 18 and be diverted 540 to drain 5 before start of fluid delivery 550. A fraction of the compensation dosage will then be lost and the dilution error will not be fully compensated for.

[0133] There is thus a time window wherein the compensation will work optimally. The width and start of this time window depend on the fill (batch) volume to deliver, and what the flush response curve will look like. This is schematically illustrated in Figs 9A, 9B, and 9C, wherein successful compensation is achieved if A2 = Al and A2 is fully delivered during the fill. These figures also illustrate how wrong compensation timing can cause incomplete delivery of A2. Similar to Fig. 8, fluid delivery to the receiving entity 3 starts at the first vertical line, at the initial dilution error limit of 2.5%, representing the delivery start concentration. The second vertical line at 1400 ml indicates a limit that could be considered to have negligible effect on the overall fill volume composition error and thus would not need any composition compensation. The diamond shape indicates start of adding 532 the compensation dosage.

[0134] Fig. 9A shows an example where compensation starts after the actual total dilution error Al has been measured. The effect of the compensation dosage A2 is indicated by the bump with a dashed line extending over 0%. The drawing also indicates that in a scenario where the batch volume to deliver is small compared to the required ultrafilter flush volume, a part of A2 may not reach the receiving entity 3 before the medical fluid delivery is stopped. For example, if the delivery is stopped after a total delivered medical fluid volume of 2500ml, a fraction of the compensation dosage A2 will not be delivered, as indicated by the see dashed area portion of A2.

[0135] Fig. 9B shows another example, with compensation starting before the actual total dilution error can be measured. Rather, the compensation dosage (e.g., the amount of the substance to be added) is determined based on assessment, as discussed. In this example, the compensation starts at or shortly after start of delivery of the medical fluid. The compensation dosage A2 is indicated by the bump with a dashed line. Earlier compensation delivery (compared to the example of Fig. 9A) decreases the risk of not having the full compensation dosage delivered during the fill. In this example, if the fill is stopped after a totally produced fluid volume of at least 2000ml, the entire compensation is delivered during the fill.

[0136] Fig. 9C shows yet another example, with compensation starting before the actual total dilution error has been measured, wherein the compensation dosage is assessed. In this example, the compensation starts before start of delivery of the medical fluid, i.e., while fluid is still diverted to drain at the outlet 13. This example indicates that too early compensation delivery increases the risk of having parts of the full compensation delivered prematurely to drain 5 before the delivery 550 has begun, see dashed area of A2.

[0137] These examples thus show preferred timing configuration of the compensation dosage according to Fig. 9B, wherein the amount of the compensation dosage is determined based on assessment. However, it should be noted that appropriately configured (in terms of timing of adding the compensation dosage) examples in accordance with Figs 9A and 9C are also conceivable, i.e., where the entire compensation dosage is delivered to the receiving entity 3 even when the compensation addition is started after (as in Fig. 9A) or before (as in Fig. 9C) initiating delivery of the medical fluid to the receiving entity 3.

[0138] Adequacy of the dilution error compensation, such as the substance amount included in the compensation dosage, may further be assessed by integrating the dilution error over the delivered volume, as described. If the delivered portion of A2 does not equal the measured or assessed Al, the difference can be used to adjust future compensation amount / magnitude A2 and / or compensation timing.

[0139] The amount of the initial fluid held in the fluid line 11, including in the hold-up volume defined by the filters 18, that may be used to form part of the delivered medical fluid may depend on different factors. For one thing, if the delivery start is based on obtaining a delivery start concentration of the substance at the outlet, as described above, at least a part of the initial fluid may be diverted to drain 5 before delivery start. This may typically be the case where there is a large deviation between the initial substance concentration and the target substance concentration, such as in the example of the initial substance concentration being zero.

[0140] As noted, various examples were outlined above for the scenario of the initial fluid contained in the fluid line 11 being the base fluid, e., water. In other examples, the initial state may instead be that the initial fluid is medical fluid (e.g., PD fluid) with a composition which deviates from the target composition demanded a next delivery / fill. The initial fluid is thus a mixture of the base fluid and the substance, wherein the initial substance concentration is different from the target substance concentration of the medical fluid to deliver. By way of example, this may be the case between different fills of a PD treatment, where concentration of an osmotic agent, e.g., glucose, is configured to change between two successive fills and associated dwells. In such a scenario, concentration of another substance, e.g., electrolytes, may be configured to be the same at these two fills.

[0141] The proposed method may thus be used to avoid complete flushing of the fluid line 11, including the hold-up volume defined by the ultrafilters 18, when the target composition is changed between fills, i.e., when the initial fluid held throughout the fluid line 11 is a mixture of the base fluid and the substance with an initial substance concentration which is different from the desired target substance concentration. By adding the compensation dosage, the initial fluid may be used to generate the medical fluid of the desired target composition. Dependent on when (timing) the composition dosage is added, e.g., as described with reference to Figs 9A-9C, all or parts of the initial fluid may be used in the delivery of the medical fluid, e.g. of a batch volume. In this example, i.e., when it is a matter of a finer adjustment between the initial substance concentration and the target substance concentration, all of the initial fluid may at least in some examples be used. In such a case, the actual initial substance concentration may be seen as the delivery start concentration. Delivery of the medical fluid may thus start upon starting generation of the medical fluid of the target substance concentration. Timing of start of adding of the compensation dosage may be before, upon or after starting generation of the medical fluid of the target concentration, in accordance with the examples described with reference to Figs 9A-9C, where timing preferably is configured such that the entire compensation dosage is delivered in the predetermined batch volume. In this context, timing of addition of the compensation dosage may be configured to avoid incomplete transport of the compensation dosage through the fluid line 11 until delivery is completed.

[0142] If the new target composition has a higher glucose (or other OA) concentration than the initial fluid, additional glucose concentrate is needed to compensate for the lower concentration of the initial fluid. The additional glucose volume of the compensation dosage can be calculated based on the glucose concentration difference between the initial substance concentration and the target substance concentration and the total volume of the fluid line 11 downstream the supply point 15 (specifically the supply point for injecting glucose).

[0143] In case the new target composition has lower glucose concentration than the initial fluid, the glucose compensation volume of the compensation dosage will be negative (i.e., of lower than the target glucose concentration).

[0144] A compensation adequacy check may further be employed, similar what was described above.

[0145] In the described cases, i.e., where glucose (or other OA) concentration is adjusted up or down, electrolyte concentration may remain the same. In other words, when glucose concentration is adjusted from that of the initial fluid, during the subsequent generation of the medical fluid with the target substance concentration and the adding of the compensation dosage, a configured ratio between the pump rate of electrolyte pump 211 and of the main pump 14 may thus be maintained.

[0146] In the foregoing, the proposed solution has been thoroughly described, and various examples and embodiments of the proposed solutions have been outlined. It may be noted that the proposed apparatus and method are not limited to holdup volumes caused by ultrafilter priming volumes but could be used to mitigate the negative effects of holdup volumes caused by any component used for whatever purpose in the fluid line. The proposed solution is based on the notion of, at start of medical fluid delivery to the receiver, allowing a certain initial composition error in the medical fluid and then compensate for the composition error by compensation dosing of concentrates during medical fluid production. As a result, a batch of correct average composition can be delivered to the receiver faster and with a significantly lowered waste of fluid and concentrates. The proposed method decreases the fluid waste and added time-to- treatment associated with ultrafilter flushing in an apparatus having ultrafilters located downstream the concentrate supply point in the apparatus. In various trials using applicant’ s equipment, concentrate waste and time-to-treatment during flushing has been shown to be decreased by 40-70%. The total concentrate consumption may thereby be decreased by 5-15%.

[0147] Going forward, various configuration examples associated with the proposed solution will be discussed, with reference to diagrams shown in the drawings, obtained by simulation. Initially, various examples are discussed in which the fluid system 11 initially contains water, and wherein generation of a medical fluid is initiated by receiving water from the inlet 12 and adding the substance (e.g., electrolytes and glucose) at the supply point 15, upstream of the hold-up volume. By way of example, the following examples refer to the specific filter setup of Fig. 4 in the apparatus 10. In these examples, the compensation dosage is referred to as a pulse, which refers to temporarily adding the substance at a compensation rate which is different from a target rate at medical fluid of the target substance concentration is generated.

[0148] Figs 10A, 10B, and 10C show diagrams related to operation without using the proposed solution. Here, c_out_mxc means concentration on the downstream side of the mixer 16, c_out_UFl means concentration on the downstream side of the first ultrafilter 181, and c_out_UF2 means concentration on the downstream side of the second ultrafilter 183, i.e., at or close to the outlet 13. Cone, error means resulting average concentration error obtained in the delivered medical fluid, and V_target indicates the point in time when a target batch (or fill) volume has been delivered.

[0149] Fig. 10B relates to Fig. 10A and illustrates the concentration error in a delivered volume where the start of the delivery occurs upon the concentration out of the second ultrafilter UF2 (183) reaching a level of 99.65% of the target concentration. The time point when the delivery starts (t_start_fill) is approximately 9.6 min. The volume (Vol) then pumped to drain is roughly 2390 ml. This corresponds to having lost concentrate that could have been used to produce ~ 73% of one target volume (2 liters in this example). As shown in Fig. 10B, the resulting concentration error in the produced volume is -0.05%. However, this is obtained at a great loss of substances, as well as a long startup time (e.g., time-to-treatment) before delivery can be initiated.

[0150] Fig. 10C corresponds to the diagram of Fig. 10B, but where delivery is instead started when the substance concentration downstream of the hold-up volume is 84% of target substance concentration. Here, t_start_fill ~ 5 min, Vol. pumped to drain ~ 1250 ml, and Cone, lost ~ 19 % of one produced volume (2 liters). A rather large concentration error of 2.47% is further obtained.

[0151] Figs 11 A and 1 IB show aspects of an example when using the proposed solution, based on using the same delivery start concentration of 84% as in the example shown in Fig. 10C. However, since compensation dosage is further added as a pulse, the delivery start concentration is reached somewhat earlier. Pulse initiated 2 min after start of pumps (i.e., start of generating medical fluid of the target concentration), lasts 1 min and adds 25% on top of the target concentration. t_start_fill ~ 4.6 min, Vol. pumped to drain ~ 1150 ml. The result is Cone, lost ~ 15 % of one produced volume (2 liters), which is an improvement. Further, the concentration error is decreased to 0.56%.

[0152] Figs 12A and 12B show another example when the proposed solution is used. Here the delivery of fluid is started much earlier, e.g. when the concentration out of the second ultrafilter has reached a set delivery start concentration which may be in the range of 20-50% of the target concentration, particularly in this example 30%. Based on the monitored concentration and the target volume the control system makes an estimation of what the concentration will be in the delivered volume. Based on this estimation, the control system further calculates what that delivered volume would lack in terms of substances and initiates a pulse representative of that deficit. In the example of Figs 12A and 12B the delivery start limit concentration of 30% is passed at t_start_fill ~ 2.8 [min] and the deficit is calculated to correspond to a pulse adding 50% more concentrate for a time duration of ~ 2.1 [min]. The results of this example is that Vol. pumped to drain ~ 700 ml and Cone, lost ~ 1.7% of one produced batch volume of 2 liters. This is a very good result from the perspective of minimizing a loss of substance (concentrate). As can be seen from Fig. 12B, the resulting concentration error in the produced batch is 0.52%.

[0153] The pulse may be configured based on the amount of the compensation dosage being assessed. One example is to define a concentration increase, which is 50% in the shown example (but may e.g., be selected within 20-100% or more), i.e. an increase of the intended target concentration. Duration of the pulse may be determined to obtain the determined amount of the compensation dosage. A lower percentage increase in the pulse leads to a longer pulse, if initiated at the same time. In the example which generated the diagrams of Figs 12A and 12B, where a 50% increase was selected for the pulse, the pulse duration was calculated to 2.08 min to make up for the substance amount that would be missing (i.e., corresponding to Al). In an alternative example, wherein the pulse was set to a 100% increase, the duration was calculated to 1.04 min, and which resulted in a further decreased error of -0.29%. In yet another example, the increase was set to 25% with a pulse duration of 4.16 min, resulting in a concentration error of -1.51%, which may still be considered to be acceptable or even good, dependent on requirements.

[0154] A method carried out according to the proposed solution, for an example corresponding to Figs 12A and 12B, may comprise the following steps

[0155] At step 500, representing an initial stage, the fluid line 11 contains water.

[0156] At step 531, generation of the medical fluid of a target substance concentration is started. This may include starting the pumps 14, 211, and 221, wherein water is drawn from the inlet 12 while the substance is added at a target rate at the supply point 15. The target rate may be obtained based on known pump ratios between pump rate / speed of the mentioned pumps, as described.

[0157] At step 550, delivery of fluid to the intended receiving entity 3 is carried out, through the outlet 13. This may be initiated at a delivery start concentration of the substance, which may be determined by monitoring conductivity 510 using the sensor 171 at the outlet 13. As noted, the delivery start concentration may be 20-50%, such as at 30%, of target substance concentration. Prior to start of delivery, fluid is diverted 540 to drain 5 downstream of the hold-up volume defined by the ultrafilter 18.

[0158] At step 520, at least some aspects of the compensation dosage may be determined. A concentration assessment level may be defined, at which level determination of at least some parameters of the compensation dosage shall be made. The level may be determined before start of generation or may even be fixed and predetermined in the control system 30. In some examples, such as the example of Figs 12A and 12B, the concentration assessment level is the same as the delivery start concentration. Alternatively, the concentration assessment level is lower, thus occurring earlier, than the delivery start concentration. Obtainment of the concentration assessment level may be determined based on monitoring 510 conductivity of the fluid using sensor 171.

[0159] The compensation dosage serves to compensate for the fact that at least some of the initial fluid held in the fluid line, i.e., water in this case, is delivered 550 to the receiving entity 3. In this context, the compensation dosage is at least partly determined based on an offset between the target substance concentration and the initial substance concentration, which is zero in this example. In this context, the compensation dosage may at least partly be determined based on the dilution error DilErr, as described. Determining the compensation dosage may comprise determining the amount of substance to add. This may include calculating what would be missing in a produced batch volume obtained from the delivery of the medical fluid based on using the pump configurations for generating the target substance concentration. This corresponds the integrated area Al, as described. In turn, this corresponds to a substance volume to be added as the compensation dosage (which is selected to result in the same integrated area of A2).

[0160] Determining the compensation dosage may further comprise determining an increased pump rate for injection of the substance, and timing of using the increased pump rate, e.g., start and a duration of the compensation dosage. In some examples, the increased pump rate may be predetermined, such as a percentage over the pump rate for obtaining the target configuration. In some examples, as described with reference to Figs 12A and 12B, start of adding the compensation dosage may also be predetermined to be at start of delivery 500 to the receiving entity 3. Based on the determined amount and the predetermined parameters of the compensation dosage, the duration may further be determined. The compensation dosage, including its timing, is determined such that the generated medical fluid delivered 550 to the receiving entity comprises at least an amount of the initial fluid and of the compensation dosage.

[0161] At step 532, the determined compensation dosage of the substance is added. Addition of the compensation dosage is obtained by increasing the pump rates of the pumps 211 and 221 relative to the main pump 14.

[0162] At step 560, delivery of the medical fluid to the receiving entity 3 is terminated. Termination may take place when a predetermined batch volume has been delivered. The compensation dosage, specifically its timing, is preferably determined such that the generated medical fluid delivered 550 to the receiving entity comprises all the substance added in the compensation dosage.

[0163] Figs 13-16 show diagrams obtained by simulation, related to various examples in which the fluid system 11 already initially contains a medical fluid, with an initial substance concentration of the substance in water, generated in a preceding stage. Generation of a medical fluid is initiated by receiving water from the inlet 12 and adding the substance (e.g., electrolytes and glucose) at the supply point 15, upstream of the hold-up volume, in an apparatus as described in the foregoing. Specifically, the initial fluid comprises an initial glucose concentration which is different from the target glucose concentration to produce. In some scenarios associated with generation of medical fluid, such as PD fluid, the target glucose concentration may typically be 1.36%, 2.27% or 3.86%.

[0164] Figs 13A and 13B relate to an example without applying the compensation dosage as a temporary pulse. In these examples, the fluid line 11 holds an initial fluid having a glucose concentration which is 1.36%, whereas the target glucose concentration is 2.27%. Fluid delivery is started directly upon start of generation of the medical fluid having the 2.27% target glucose concentration. However, as can be seen from Fig. 13B, by simply applying the 2.27% injection rate of the glucose pump 221, the resulting concentration error in the produced volume would then be -18.47%. Calculations indicate that when the batch volume is produced, about 0.838 mmol of glucose is lacking to get to 2.27 mmol / 1. This would typically not represent an acceptable outcome.

[0165] Figs 14A and 14B correspond to the scenario of Figs 13A and 13B, by relating to changing the glucose concentration from 1.36% to 2.27%. However, in this case, this is obtained by adding the compensation dosage as a pulse with a duration of 2.1 minute, while not wasting any fluid. This example is based on the supply arrangement 20 (specifically the pump 221) already having a configured injection rate setting for obtaining 3.86%, wherein this injection rate may be used to increase the concentration in the delivered fluid while not wasting any fluid. The amount of the compensation dosage may then be obtained as an estimate of how much glucose would be lacking after delivering a batch volume (2 liters) directly when pumps are started. This means Vol. pumped to drain = 0 ml, and injection rate of the glucose pump 221 is increased to obtain 3.86%, i.e. the upper concentration used. The 2.1 minute pulse is based on the amount of glucose would be lacking in the produced batch volume: Lacking is ~ 0.838 [mmol], and (3.86-2.27) [mmol / 1] * 0.25 [1 / min] * 2.1 [minute] = 0.835 [mmol] (hatched area).

[0166] As can be seen in Fig. 14B, the resulting concentration error in the produced volume would be -0.79%, which can be seen as an acceptable result.

[0167] It will be clear to the skilled person that corresponding configurations may be provided for increasing from 1.36% or 2.27% to 3.86% too, by configuring a pulse of the compensation dosage, based on the amount of glucose that would be lacking in the produced batch volume without the pulse and only generating the medical fluid with the target concentration of 3.86% as baseline. The glucose pump may then be configured to increase its injection rate to temporarily generate medical fluid with a glucose level of e.g., 5-10% for a duration determined to cover the glucose that would be lacking in the produced batch volume.

[0168] It will be clear to the skilled person that the parameters of delivery start concentration and pulse increase level, which together define the amount (corresponding to A2=A1 as described above) and the pulse duration of the compensation dosage, may be configured in a variety of different ways. In some embodiments, these parameters are set so that the substance added by the compensation dosage is completely delivered in a predetermined batch volume.

Claims

CLAIMS1. A method for generating a medical fluid in a fluid line comprising an inlet for receiving a base fluid, a supply point for adding a substance, a hold-up volume downstream of the supply point, and an outlet for delivering the medical fluid comprising a mixture of the base fluid and the substance, said method comprising: holding (500) an initial fluid in the fluid line; starting (531) generation of the medical fluid of a target substance concentration based on receiving base fluid in the fluid line while adding the substance at a target rate; adding (532), based on an offset between the target substance concentration and initial substance concentration of the initial fluid, a compensation dosage of the substance into the fluid line; and delivering (550), from the outlet to a receiving entity, the generated medical fluid comprising at least an amount of the initial fluid and of the compensation dosage.

2. The method of claim 1, wherein adding comprises temporarily adding the substance at a compensation rate which is different from the target rate.

3. The method of claim 1 or 2, wherein adding the compensation dosage is started at a delayed time point after starting generation of the medical fluid of the target substance concentration.

4. The method of claim 1 or 2, wherein adding the compensation dosage is started upon starting generation of the medical fluid of the target substance concentration.

5. The method of any preceding claim, wherein delivering is carried out until a batch volume of the medical fluid has been fed to the receiving entity.

6. The method of any preceding claim, comprising: diverting (540) fluid to drain from the fluid line at the outlet at the start of generation of the medical fluid, wherein the delivery to the receiving entity is started upon obtaining a delivery start concentration of the substance at the outlet.

7. The method of claim 6, wherein the delivery start concentration is different from the target substance concentration.

8. The method of any preceding claim, wherein the delivery to the receiving entity is started upon start of adding of the compensation dosage.9 The method of any of claims 1-7, wherein the delivery to the receiving entity is started prior to start of adding of the compensation dosage.

10. The method of any of claims 1-7, wherein the delivery to the receiving entity is started after start of adding of the compensation dosage.

11. The method of any preceding claim, wherein the base fluid is water and the substance comprises a substance component including an electrolyte.

12. The method of any preceding claim, wherein the initial fluid is the base fluid, said initial substance concentration being zero.

13. The method of any of claims 1-10, wherein the base fluid is water and the substance comprises a substance component including an osmotic agent.

14. The method of claim 11 or 13, wherein the initial fluid is a mixture of the base fluid and the substance, wherein the initial substance concentration of the substance component is different from the target substance concentration of the substance component.

15. The method of any preceding claim, wherein the compensation dosage is diluted in the hold-up volume.

16. The method of any preceding claim, comprising: determining (520) substance concentration at the outlet by measuring conductivity of the medical fluid.

17. The method of any preceding claim, comprising: pre-characterizing dynamics of the fluid line by adding a pulse of the substance at a predetermined rate upon the initial fluid being the base fluid, and determining substance concentration by measuring conductivity at the outlet while pumping in the fluid line; and determining timing and volume of the compensation dosage based on the precharacterized dynamics and said offset.

18. An apparatus (10) configured to generate a medical fluid comprising a mixture of a base fluid and a substance, said apparatus comprising: a fluid line (11) extending from an inlet (12) for receiving the base fluid to an outlet (13) for delivering the medical fluid, said fluid line comprising a hold-up volume; a supply arrangement (20) fluidly connected at a supply point (15) in the fluid line, upstream of the hold-up volume, to add the substance into the fluid line; and a control system (30) configured to control the apparatus to start generating the medical fluid, wherein the supply arrangement is controlled to add the substance at a target rate for mixing with base fluid received from the inlet to obtain a target substance concentration, wherein the control system is further configured to control the supply arrangement to add, based on an offset between the target substance concentration and an initial substance concentration of an initial fluid held in the fluid line at said start, a compensation dosage of the substance into the fluid line; and wherein the outlet is connected to a receiving entity to deliver the generated medical fluid comprising at least an amount of the initial fluid and of the compensation dosage.

19. The apparatus of claim 18, wherein the control system is further configured to operate in accordance with any of claims 2-17.

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