Apparatus and method for generating a medical fluid

Abstract

A method and an apparatus (10) usable for online generation of medical fluid in a fluid main line (11) extending from a base fluid inlet point (12) to a medical fluid outlet point (13). The medical fluid comprises a mixture of a base fluid and at least one concentrate, and may be a dialysis fluid. The method includes operating a batch generation phase comprising: connecting a recirculation line (50) to a portion (53) of the main line, said portion comprising a fluid pump (14), a supply point (15) of concentrate delivery to the main line, and a hold-up volume (18) downstream the supply point, wherein a fluid loop (60) comprising said portion and the recirculation line is obtained; controlling, based on a determined fluid composition in the fluid loop, delivery of the concentrate at the supply point to form the medical fluid with a target composition in the fluid loop.

Description

[0001] APPARATUS AND METHOD FOR GENERATING A MEDICAL FLUID

[0002] Technical Field

[0003] The present disclosure generally relates to the field of generating a medical fluid, such as a dialysis fluid. The proposed solution may be set out in an apparatus configured for online generation of a medical fluid during which a continually supplied base fluid is mixed with a concentrate to obtain and subsequently deliver the medical fluid. According to the proposed solution, an apparatus and a method are provided, capable of operating a batch generation phase for generating the medical fluid based on fluid present in the apparatus. The fluid present in the apparatus may comprise remaining medical fluid from online generation or pure base fluid after rinsing.

[0004] Background

[0005] Medical fluids may be used in therapeutic treatment of a patient. This applies, inter alia, to 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.

[0006] Different medical fluids may be used depending on the type of dialysis treatment.

[0007] One type of kidney failure therapy is Hemodialysis (“HD”), which in general uses diffusion 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 the dialysis machines by mixing concentrates and clean water.

[0008] Hemofiltration (“HF”) is an alternative renal replacement therapy that relies on a 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.

[0009] Hemodiafiltration (“HDF”) is a treatment modality that combines convective and diffusive clearances. HDF uses dialysis fluid as the medical fluid, flowing through a dialyzer, similar to standard hemodialysis, to provide diffusive clearance. In addition, substitution solution is delivered directly to the extracorporeal circuit, providing convective clearance. Here, more fluid than the patient’s excess fluid is removed from the patient, causing the increased convective transport of waste products from the patient. The additional fluid removed is replaced via the substitution or replacement fluid.

[0010] Another 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. 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.

[0011] As indicated, the 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.

[0012] As an alternative, various types of devices have been suggested, which are capable of producing the medical fluid using a base fluid, typically fresh and pre-treated water, and proper concentrates. In this context, the medical fluid is generated by, inter alia, mixing the concentrates with the base fluid in the apparatus. An aspect of using such an apparatus for generating the medical fluid is that the composition of the medical fluid typically needs to be determined and controlled within specified or reasonable tolerances, before it can be used for the intended therapeutic scenario. Moreover, between different occasions of using the apparatus, the apparatus will normally be properly cleaned, which may involve flushing fluid paths in the apparatus with a cleaning agent, such as purified water.

[0013] Upon initiating a stage of medical fluid generation, the apparatus may thus already contain a certain amount of fluid, such as a medical fluid of a previously generated composition, or predominantly water remaining from a cleaning stage. The contained fluid remaining in the apparatus may thus need to be replaced with freshly made medical fluid of a certain target concentration, generated in the apparatus, before the medical fluid can be used as intended. For these reasons, at least the contained fluid normally needs to be purged as waste, e.g., to drain.

[0014] Summary

[0015] It is an objective to at least partly overcome one or more limitations of the prior art. One objective is to provide a technical solution for minimizing waste of fluid and of user effort in the process of generation and use of the medical fluid, inter alia associated with the generation of a dialysis fluid.

[0016] One or more of these objectives, as well as further objectives that may appear from the description below, are at least partly achieved by an apparatus configured to generate a medical fluid, said apparatus comprising: a fluid main line extending from a base fluid inlet point to a medical fluid outlet point; a fluid pump configured to pump fluid in the main line; a concentrate supply arrangement fluidly connected at a supply point on the main line; and a control system configured to operate the apparatus in an online generation phase comprising to control the concentrate supply arrangement to continuously or continually deliver at least one concentrate at the supply point for mixing with the base fluid in the main line to form the medical fluid with a target composition to be delivered at the medical fluid outlet point; the apparatus further comprising a fluidly connectable recirculation line configured to form a fluid loop together with a portion of the main line, which portion comprises the fluid pump, the supply point, and a hold-up volume in the main line downstream of the supply point; wherein the control system is configured to operate the apparatus in a batch generation phase comprising to control the concentrate supply arrangement to deliver the concentrate at the supply point based on a determined fluid composition of the fluid in the fluid loop, to form a medical fluid with a target composition in the fluid loop.

[0017] As a result of the proposed solution, the apparatus is configured to reuse fluid contained as hold-up volume in the batch generation phase, by recirculating the fluid and delivering the concentrate to form a medical fluid with the intended target composition in the fluid loop. This minimizes the need to waste fluid contained in the apparatus, which may remain e.g., after cleaning or after previously generating (producing) medical fluid of a different composition. Moreover, this may minimize use of concentrates, and thus handling (changing and storing) of concentrate bags over time.

[0018] According to some embodiments, the control system is configured to control the concentrate supply arrangement based on a sensed property indicative of the fluid composition in the fluid loop.

[0019] According to some embodiments, the control system comprises a sensor arranged in the fluid loop, configured to sense said property.

[0020] According to some embodiments, said sensor is arranged in said portion.

[0021] According to some embodiments, the apparatus further comprises a mixing chamber arranged in said portion.

[0022] According to some embodiments, the hold-up volume is at least partially defined by one or more filter chambers in said portion of the main line.

[0023] According to some embodiments, the apparatus further comprises a valve arrangement, wherein the control system is configured to control the valve system in the batch generation phase to obtain: fluid connection of the recirculation line to the main line, and fluid disconnection of said portion from the medical fluid outlet. According to some embodiments, the control system is configured, upon obtaining the target composition of the medical fluid, to control the valve system to obtain: fluid disconnection of the recirculation line from to the main line, and fluid connection of said portion to the medical fluid outlet.

[0024] According to some embodiments, in the batch generation phase, the control system is configured to: calculate an amount of concentrate to deliver based on the determined fluid composition; add, using at least the concentrate supply arrangement, a volume of fluid comprising the calculated amount of concentrate, to the fluid loop.

[0025] According to some embodiments, in the batch generation phase, the control system is configured to iteratively: calculate an amount of concentrate to deliver based on the determined fluid composition; add, using at least the concentrate supply arrangement, a volume of fluid, comprising the calculated amount of concentrate, to the fluid loop; to achieve said target composition.

[0026] According to some embodiments, the added volume of fluid further comprises said base fluid.

[0027] According to some embodiments, the control system is configured to: purge a corresponding volume of fluid from the fluid loop at a connection downstream of the hold-up volume.

[0028] According to some embodiments, the control system is configured to calculate the amount based on a determined fluid volume present in the fluid loop.

[0029] According to some embodiments, the concentrate supply arrangement comprises: a first subunit configured to supply a first concentrate including an electrolyte, and a second subunit configured to supply a second concentrate including an osmotic agent, wherein the fluid composition is determined based on sensed electrical conductivity of the fluid in the fluid loop. According to some embodiments, each subunit comprises a volumetric pump, configured to deliver the respective concentrate.

[0030] According to another aspect, the proposed solution provides a method for generating a medical fluid comprising a mixture of a base fluid and at least one concentrate in an apparatus usable for online generation of medical fluid in a fluid main line extending from a base fluid inlet point to a medical fluid outlet point, wherein said method includes operating a batch generation phase comprising: connecting a recirculation line to a portion of the main line, said portion comprising a fluid pump, a supply point of concentrate delivery to the main line, and a hold-up volume downstream the supply point, wherein a fluid loop comprising said portion and the recirculation line is obtained; controlling, based on a determined fluid composition in the fluid loop, delivery of the concentrate at the supply point to form the medical fluid with a target composition in the fluid loop.

[0031] As a result of the proposed solution, the method is configured to reuse fluid contained as hold-up volume in the batch generation phase, by recirculating the fluid and delivering the concentrate to form a medical fluid with the intended target composition in the fluid loop. This minimizes the need to waste fluid contained in the apparatus, which may remain e.g., after cleaning or after previously generating (producing) medical fluid of a different composition. Moreover, this may minimize use of concentrates, and thus handling (changing and storing) of concentrate bags over time.

[0032] According to some embodiments, the method further comprises an initial step of: priming at least the main line with the base fluid.

[0033] According to some embodiments, concentrate delivery is controlled based on a sensed property indicative of the fluid composition in the fluid loop.

[0034] According to some embodiments, the hold-up volume is at least partially defined by a filter chamber in the main line.

[0035] According to some embodiments, connecting comprises: fluidly connecting the recirculation line to the main line, and fluidly disconnecting said portion from the medical fluid outlet.

[0036] According to some embodiments, the method further comprises, upon obtaining the target composition of the medical fluid in the fluid loop: fluidly disconnecting the recirculation line from the main line, and fluidly connecting said portion to the medical fluid outlet.

[0037] According to some embodiments, controlling comprises: calculating an amount of concentrate to deliver based on the determined fluid composition; adding a volume of fluid, comprising the calculated amount of concentrate, to the fluid loop.

[0038] According to some embodiments, controlling comprises iteratively: calculating the amount of concentrate to deliver based on the determined fluid composition; adding a volume of fluid, comprising the calculated amount of concentrate, to the fluid loop; to achieve said target composition.

[0039] According to some embodiments, the added volume of fluid further comprises said base fluid.

[0040] According to some embodiments, the method further comprises: purging a corresponding volume of fluid from the fluid loop at a connection downstream of the hold-up volume.

[0041] According to some embodiments, calculating is based on a determined fluid volume present in the fluid loop

[0042] According to some embodiments, controlling comprises: a first stage of controlling delivery of an electrolyte concentrate in the fluid loop, and a second stage of controlling delivery of an osmotic agent concentrate and the electrolyte concentrate in the fluid loop.

[0043] 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 a fluid inlet and mixed with a concentrate, to form the medical fluid which is passed to a medical fluid outlet.

[0044] Fig. 2 schematically illustrates a control system for use in an apparatus according to various examples of the proposed solution. Fig. 3 schematically illustrates an example of a concentrate supply arrangement, for use in an apparatus according to various examples of the proposed solution.

[0045] Fig. 4 schematically illustrates a filter setup in an apparatus according to various examples of the proposed solution, wherein the filter setup comprises two ultrafilters with respective filter chambers.

[0046] Fig. 5 is a schematic view of a fluid circuit associated with an apparatus according to the proposed solution, capable of operating in a batch generation phase to produce a medical fluid based on fluid held in the apparatus from a previous process, such as a priming process or a previous process of generating a medical fluid.

[0047] Fig. 6 schematically illustrates various parts of the apparatus of Fig. 5, when configured to operate according to the batch generation phase.

[0048] Fig. 7 is a flow chart showing various steps included in different examples of a method according to the proposed solution, for batch generation of a medical fluid in an apparatus capable of online generation of the medical fluid.

[0049] Detailed Description

[0050] 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.

[0051] 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.

[0052] 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.

[0053] 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.

[0054] Well-known functions or constructions may not be described in detail for brevity and / or clarity. Unless otherwise defined, all terms (including technical and scientific terms) used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs.

[0055] The present disclosure generally relates to generation of a medical fluid, in particular a medical fluid usable in dialysis treatment. 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 peritoneal dialysis (PD) therapy. Various aspects of the present disclosure relate to 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 (peritoneal dialysis) fluid to be directed to, e.g., a cycler for peritoneal dialysis treatments. While the present disclosure focuses more on PD fluid, 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.

[0056] For context, 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 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 disconnects the catheter from the fresh dialysis fluid bag 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.

[0057] 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 and for the transfer of waste, toxins, and excess water to 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.

[0058] 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 and 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.

[0059] 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 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.

[0060] 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.

[0061] The apparatus 10 has a fluid circuit which comprises a fluid main line 11, indicated by the thicker line in the drawing. The fluid circuit, including the main 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 main line 11 extends from a base fluid inlet point 12 to a medical fluid outlet point 13. The inlet point 12 thus acts as an interface configured to receive a base fluid from a base fluid source. For this purpose, the inlet point 12 may comprise a connector or port for a hose, tube, or the like.

[0062] 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 point 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 point 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”.

[0063] 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 point 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 the supplied concentrate(s), whereas the exact nature and definition of the target composition is not crucial. 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.

[0064] The outlet point 13 provides an interface configured to deliver generated medical fluid to a receiving entity 3. For this purpose, the outlet point 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.

[0065] The apparatus 10 comprises a fluid pump 14, also referred to herein as a main pump 14, configured to pump fluid in the main line 11. The main pump 14 is predominately operated to pump fluid forward, or downstream, in the main line 11, i.e. from the inlet point 12 to the outlet point 13, but may in some examples additionally be operated in the opposite direction, so as to pump or drag fluid from the outlet point 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 main line 11 to provide feedback in a control circuit to ensure a desired flow rate.

[0066] The apparatus further comprises a concentrate supply arrangement 20, fluidly connected at a supply point 15 on the main line 11. The concentrate supply arrangement 20 has an inlet connected to receive at least one type of concentrate, or additive, from a concentrate source 4 connected to the apparatus 10, such as a bag or other container. The concentrate may be received in the concentrate supply arrangement 20 in liquid form, as a gel, pellets, or other. The concentrate supply arrangement 20 is further configured to add 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 concentrate supply arrangement 20 may comprise at least one concentrate pump.

[0067] The apparatus 10 may further comprise a mixer including a mixing chamber 16, which may comprise a motorized or flow-driven mechanism for mixing the concentrate with the base fluid. The mixing chamber 16 is arranged for mixing fluids in the main line 11.

[0068] 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 main line 11.

[0069] The apparatus may further comprise at least one filter 18, such as an ultrafilter, which is intended to reduce or remove microbials and endotoxins from the finally mixed medical fluid prior to fluid delivery at the outlet point 13. The filter 18 may comprise at least one chamber, capable of holding a volume of fluid.

[0070] The apparatus may further comprise a valve arrangement 19, four valves being indicated in the drawing by way of example. The valve arrangement may be controlled to, inter alia, selectively connect or disconnect fluid communication to the outlet point 13, and to selectively purge fluid from the main line 11, e.g., to drain 5. The valve arrangement 19 may comprise a plurality of valves configured to operate on the fluid circuit to set different fluid paths, in particular according to different processes and operations to be executed by the apparatus 10. In general, a valve has an open state allowing fluid passage and a closed state preventing fluid passage. 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.

[0071] 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 is continuously produced from concentrates and base fluid in the main line 11 to be continuously delivered at the outlet point 13. The medical fluid is thus produced “inline”. The control system 30 controls the concentrate 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 main line 11 to form the medical fluid with a target composition to be delivered at the outlet point 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 to adapt control of the elements and functions in the apparatus 10 based on said input. 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.

[0072] 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.

[0073] 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, such as sensor 17 and possibly additional sensors for sensing pressure, temperature, flow, or other properties of the fluid in the main line 11. The interface 34 may further be configured for providing control output to, inter alia, the concentrate supply arrangement 30, the main pump 14, the valves of the valve arrangement, 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.

[0074] Fig. 3 schematically illustrates an embodiment of the concentrate supply arrangement 20, which may be useful in e.g., an apparatus 10 configured for generation of a PD fluid. In this embodiment, the concentrate supply arrangement 20 comprises, at least, two subunits 210 and 220.

[0075] A first subunit 210 is configured to supply a first concentrate EC (Electrolyte Concentrate) 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 main 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.

[0076] A second subunit 220 is configured to supply a second concentrate OAC (Osmotic Agent Concentrate) 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 main 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.

[0077] The concentrate 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 level 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 level may be based on sensor feedback to the control system 30 from the sensor 17.

[0078] Fig. 4 schematically illustrates an embodiment of the filter 18 arranged in the main 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 point 13. Fig. 4 shows an example with two successive filters 181, 183 connected in the main 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.

[0079] Using filter 181 as reference by way of example, the ultrafilter 181 has 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(s) 182, 184 may comprise a considerable hold-up volume of fluid in the apparatus 10, in particular compared to other entities along the main line 11.

[0080] 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. However, this configuration, wherein a large hold-up volume (compared to the other components on the main 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. Where a hold-up volume (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 will act as a buffer volume which content would need to be replaced (flushed) more or less completely every time the solution generation device changes its target fluid composition. This means increased medical fluid waste and time consumption. For example, if the ultrafilter chamber(s) 182, 184 initially contain purified water after a heat disinfection sequence, and the receiving device 3 demands medical fluid of a certain target composition, the water in the ultrafilters needs to be flushed out with said medical fluid until the fluid composition after the ultrafilters matches the target composition. Due to internal mixing in the ultrafilters, the required flush volume typically much exceeds the ultrafilter priming volume.

[0081] Another example is when the target composition of the medical fluid is changed, e.g., between patient fills in a PD treatment. This typically means that the target concentration of OA, such as glucose, is changed. Although the concentration change is less than in the previous example, a similar flush is required before the medical fluid can be administered at the target composition to the patient.

[0082] PD fluid waste means that PD concentrate is wasted, which means an added cost. Also, the added time consumption for flushing could mean that the time to treatment will increase in case disinfection water is to be flushed out with PD fluid before treatment start.

[0083] Fig. 5 illustrates an example of an apparatus 10 for generating a medical fluid according to the proposed solution, which apparatus is configured to alleviate drawbacks associated with the prior art, as outlined in the foregoing. In this context, the apparatus 10 is configured to enable operation of a batch generation phase, in which fluid held in at least the main fluid line with its included entities, such as the hold-up volume held in the chamber(s) of the filter(s) 18 may be reused, e.g., in connection with initiating a subsequent online generation phase. For the sake of convenience, the reference numerals as used in the foregoing are reused in Fig. 5, to indicate corresponding features and entities.

[0084] The apparatus 10 comprises a recirculation line 50 which is fluidly connectable to the main line 11 to form a fluid loop 60 together with a portion 53 of the main line 11. In the drawing of Fig. 5, the recirculation line 50 is indicated by a double line. As for the main fluid line 11, the recirculation line 50 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 recirculation line 50 extends between a first connection point 51 in the main line 11 and a second connection point 52 in the main line 11. The part of the main line 11 which extends between said first connection point 51 and said second connection point 52, forms said portion 53 of the main line 11. Fig. 6 shows a subset of the elements included in the apparatus 10 according to Fig. 5, to more clearly illustrate the formation of the fluid loop 60. A recirculation path 61 of fluid in the fluid loop 60 is schematically indicated by the dashed arrowed central symbol. It should be noted, though, that in various examples, circulation using the recirculation line 50, as driven by the main pump 14, may in various scenarios be carried out in the reversed direction. In this drawing, the whole fluid loop 60, comprising the recirculation line 53 and the portion 53 of the main line 11, which portion 53 extends between said first connection point 51 and said second connection point 52, is indicated by a double line.

[0085] The portion 53 of the main line 11 comprises the fluid pump 14, the supply point 15, and a hold-up volume in the main line downstream of the supply point 15. The holdup volume may comprise fluid (liquid) volume defined by the combined conduits and entities of the portion of the main line 11 after the supply point 15.

[0086] 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. The portion 53 of the main line 11, optionally also including the recirculation line 50, can be considered to define the internal volume, or system volume, for holding fluid in the apparatus 10.

[0087] 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 lines 11 and 50, for example the mixing chamber 16, filter 18 and / or conduits of the lines 11, 50 themselves. Conduits of the fluid loop 60 which are comparatively narrow, such as tubes or pipes, will not add to the problem of waste of medical fluid (or concentrates) 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) of the filter(s) 18.

[0088] In the drawings of Figs 5 and 6, a valve 191 is further schematically shown, to indicate that the recirculation line 50 is configured to selectively enable fluid connectivity in the fluid loop 60. Hence, the valve 191 is arranged to selectively allow a flow or stop a flow in the fluid loop 60. In Fig. 5, the valve 191 is arranged in the recirculation line 50. Additionally, a valve 192 is arranged in the main line 1 Ito control fluid access from the main line 11 to the outlet point 3. In Fig. 5 the valve 192 is arranged in the main line 11 downstream the first connection point 51. However, it should be understood that the valve arrangement 19 may comprise additional valves connected to selectively open or close fluid connectivity to the recirculation line 50.

[0089] In an online generation phase, the control system 30 may thus be configured to control the valve system 19 to obtain: fluid disconnection of the recirculation line 50 to the main line 11, e.g., by operating valve 191, and fluid connection of said portion 53 of the main line 11 to the medical fluid outlet 13, e.g., by operating valve 192.

[0090] In this control state of the valve system 19, base fluid may thus be continually received from the fluid inlet 12 and mixed in the main line 11 with a concentrate continually injected at the supply point 15 to obtain the medical fluid, wherein the medical fluid is delivered out via the fluid outlet 13.

[0091] According to an aspect of the proposed solution, the control system 30 is configured to operate the apparatus 10 in a batch generation phase comprising to control the concentrate supply arrangement 20 to deliver the concentrate at the supply point 15 based on a determined fluid composition of the fluid in the fluid loop 60, to form a medical fluid with a target composition. In some examples, the total fluid loop 60 forms a reservoir which defines the volume of one batch. In this context, the apparatus 10 is configured to form a medical fluid with the target composition using fluid recirculated from the hold-up volume, which may be dominated by the fluid volume in the chamber(s) of the filter 18.

[0092] In the batch generation phase, the control system 30 may thus be configured to control the valve system 19 to obtain: fluid connection of the recirculation line 50 to the main line 11, e.g., by operating valve 191, and fluid disconnection of said portion 53 of the main line 11 from the medical fluid outlet 13, e.g., by operating valve 192.

[0093] By including the ultrafilters hold-up volume in fluid loop 60 which forms a mixing recirculation path, the fluid composition of the hold-up volume can be compensated by concentrate and / or water addition to match the target composition, e.g., what is demanded by a dialysis fluid administration device 3. The compensated fluid contained in the fluid loop 60 may then be directly used (e.g., administered to a patient) without a need to flush the filter(s) 18.

[0094] In some embodiments, the control system 30 is configured to control the concentrate supply arrangement 20 based on a sensed property indicative of the fluid composition in the fluid loop. In some embodiments, for example where the concentrate supply arrangement 20 is configured to supply an electrolyte concentrate EC, the fluid composition is determined based on sensed electrical conductivity of the fluid in the fluid loop 60.

[0095] The sensed property may be obtained from the sensor 17 arranged in the fluid loop, configured to sense said property. The sensor 17 may be arranged in said portion 53 of the main line 11. This way, the same sensor may additionally be used in online production of the medical fluid, i.e., without using recirculation in the fluid loop 60. In the drawings, the sensor is placed after the supply point 15 and the mixing chamber 16, but prior to the filter 18. In an alternative arrangement, the sensor may be positioned on the portion 53 after / downstream the filter 18, to sense the property of the fluid in the fluid loop 60. In yet another alternative arrangement, a dedicated sensor for batch generation phase use may be arranged to sense the property of the fluid in the recirculation line 50.

[0096] In various embodiments, when the apparatus 10 is arranged to operate in the batch generation phase, the control system is configured to calculate an amount of concentrate to deliver based on the determined fluid composition, and to add a volume of fluid comprising the calculated amount of concentrate to the fluid loop. This may involve adding the concentrate using the concentrate supply arrangement 20, and optionally also adding base fluid from the base fluid inlet 12. The control system 30 may further be configured to purge, i.e. expel, a corresponding volume (as the added volume) of fluid from the fluid loop. In some examples, this is obtained at a connection downstream of the hold-up volume, which may be defined as the filter 18, so as to favor purging of fluid of the previously present composition rather than purging the freshly added volume of fluid. With reference to Fig. 5, this may in various examples be executed by selectively opening valve 195. In other examples, where the main pump 14 is configured to circulate the fluid in the fluid loop 60 in a direction opposite to what is indicated in Fig. 6, purging of fluid may instead be carried out using any of valves 193 or 194.

[0097] As has been noted, the comparatively large hold-up volume in the main line 11, as defined (at least primarily) by the chamber(s) of the filter 18, will lead to mixing of the concentrate also in the hold-up volume. To obtain proper homogenization of the composition throughout the fluid loop 60 (i.e., the same concentration in every part of the fluid in the fluid loop), the control system 30 may be configured to drive the pump 14 to recirculate the fluid, with the fluid amount added based on the calculation, one or more times / laps in the fluid loop 60.

[0098] Calculation of the amount to be added may be based on a determined fluid volume present in the fluid loop 60. In this context, the fluid volume shall be understood as the liquid volume, i.e., not counting air or other gas present in the fluid loop 60. It may be noted that e.g., filters 18 may be exchanged regularly, and that the true volume of the filter chamber(s) 182, 184 may in some scenarios not be known with sufficient accuracy to properly calculate the amount of concentrate to add, to ensure that the target composition is obtained with a certain concentration accuracy, as prescribed or otherwise defined. Additionally, a level of air present in the fluid loop, particularly in the filter(s) 18, may not be accurately known. In some examples, the determined fluid volume level in the fluid loop may thus initially be a predetermined assessment of the volume. In this context, the control system 30 may be configured to calculate, and control the concentrate supply arrangement 20 to deliver, a first amount of concentrate based on said assessed volume of the fluid loop. Upon circulating the fluid to obtain even concentration in the fluid loop 60, and subsequently measuring the obtained concentration (e.g., based on output from the sensor 17), the control system may be enabled to determine a more correct value of the fluid volume in the fluid loop 60, based on the noted concentration change. The control system 30 may thus be configured to calculate, and control the concentrate supply arrangement 20 to deliver, a second amount of concentrate based on the noted concentration change.

[0099] In some examples, the control system 30 is configured to operate the batch generation phase according to an iterative process, where each iteration is based on the present fluid composition (concentration) in the fluid loop.

[0100] A first iteration may comprise calculating, and adding, a first amount of concentrate to the fluid loop 60, where the calculation is based on the determined fluid composition and an assessment of the fluid volume in the fluid loop 60.

[0101] A second iteration may be based on a new determination of the fluid composition, obtained responsive to the addition of concentrate in the first iteration. The second iteration may further comprise calculating, and adding, a second amount of concentrate to the fluid loop 60, where the calculation is based on the new determined present fluid composition and the concentrate change obtained by the addition of the previous (first) amount of concentrate, where this concentrate change is indicative of the true fluid volume in the fluid loop 60.

[0102] In some examples, the calculation carried out in the control system 30 in the second iteration may be carried out with the objective to obtain the target composition in the fluid of the fluid loop 60 after the second iteration. In some examples, the calculation carried out in the control system 30 in the second iteration may be carried out with the objective to not exceed the target composition in the fluid of the fluid loop 60 after the second iteration.

[0103] If the concentration, indicative of the fluid composition, after the second iteration is still outside a certain accuracy level of the target composition, the control system may be configured to carry out an additional iteration. Iteration may halt when the determined obtained composition is within the accuracy level of the target composition. In various examples, this may be determined by taking any known further volume between the first connection point 51 and the fluid outlet point 13 into consideration, which may contain fluid of the concentration determined at the beginning of the batch generation phase.

[0104] It may further be noted that each iteration may involve circulating the fluid in the fluid loop 60 to obtain even concentration in the fluid throughout the fluid loop 60.

[0105] In the context of these examples, the control system 30 of the apparatus 10 may thus be configured to iteratively: determine the fluid composition in the fluid loop; calculate an amount of concentrate to deliver based on the determined fluid composition; add, using at least the concentrate supply arrangement, a volume of fluid, comprising the calculated amount of concentrate, to the fluid loop; so as to achieve said target composition.

[0106] The iteration according to the foregoing may, for the purpose of generation of a PD fluid, comprise addition of EC using subunit 210 and / or OAC using the subunit 220. Various examples will be described below, related to a method according to the proposed solution.

[0107] The batch generation phase may be deemed to be over when the target composition has been obtained in the fluid in the fluid loop 60. As noted, this may comprise reaching a final composition which is within a certain tolerance threshold associated with the target composition, which as such may include a plurality of different tolerance thresholds for different components of the medical fluid, e.g., associated with a concentration of electrolytes and a concentration of the osmotic agent, such as glucose. Upon termination of the batch generation phase, the apparatus may be configured for an online generation phase. The control system 30 may thereby be configured to control the valve system 19 to obtain fluid disconnection of the recirculation line 50 from to the main line 11, and fluid connection of said portion 53 to the medical fluid outlet 13. This may involve controlling the valve 192 to open fluid communication, and optionally also closing valve 191.

[0108] Various examples related to a method according to the proposed solution will now be described. It shall be noted that the method may in some examples be carried out using the apparatus 10 described in the foregoing, to which reference will occasionally is made. Description of various features and steps outlined with reference to the apparatus 10 in the foregoing are equally applicable to the method discussed below.

[0109] An example of the method according to the proposed solution is represented by the flow chart of Fig. 7.

[0110] As indicated in step 700, an apparatus usable for online generation of a medical fluid may be provided, in which apparatus the method is set out.

[0111] The method is thus provided for generating a medical fluid comprising a mixture of a base fluid and at least one concentrate in an apparatus usable for online generation of medical fluid in a fluid main line extending from a base fluid inlet point to a medical fluid outlet point.

[0112] The method is specifically characterized by operating a batch generation phase for the purpose of using fluid already present in the apparatus, which fluid is of another composition than a desired target composition of the medical fluid.

[0113] Step 705 indicates that the steps characterizing the batch generation phase may in some examples be preceded by an online generation phase, in which a medical fluid of a 1sttarget composition may have been produced. After step 705, the main line holds medical fluid of the 1sttarget composition.

[0114] In certain examples of the method, different stages of producing and delivering medical fluid may be carried out within a common treatment, with different target composition. This may, inter alia, be the case with different successive fill cycles of one PD treatment of a patient. The composition of the medical fluid may then have to be altered between such fills.

[0115] Step 710 indicates connecting a recirculation line to a portion of the main line, said portion comprising a fluid pump, a supply point of concentrate delivery to the main line, and a hold-up volume downstream the supply point, wherein a fluid loop comprising said portion and the recirculation line is obtained. The supply point thus serves to deliver the concentrate to the fluid in the main line, which may be the base fluid (e.g., water) or a mixture of the base fluid and the concentrate.

[0116] Connecting may comprise fluidly connecting the recirculation line to the main line, and fluidly disconnecting said portion from the medical fluid outlet. This may include operating one or more valves.

[0117] Step 720 provides an optional step of priming at least the main line with the base fluid. Typically, this may involve flushing and filling the entire main line with purified water. Water flushing of all mixing lines and volumes, including filters, serves the purpose of replacing water used for disinfection, which may comprise some endotoxin content, with pure water. This step may be carried out before a new treatment, rather than between different fills of a common treatment as discussed with reference to step 705. In some examples, the priming also involves flushing and filling the recirculation line 50 with purified water

[0118] Step 730 indicates the step of controlling, based on a determined fluid composition in the fluid loop, delivery of the concentrate at the supply point to form the medical fluid with a target composition in the fluid loop. This may involve operating the fluid pump to circulate the fluid in the fluid loop and measuring a physical property indicative of the composition, until the composition, e.g., concentration (measured as conductivity), is stable. In this step, medical fluid is generated based on at least fluid recirculated from the hold-up volume in the fluid loop, which may be predominantly defined by a filter, such as one or more ultrafilters.

[0119] In various examples, controlling comprises the following sub steps:

[0120] Where the controlling 730 begins with the main line (and the recirculation line) being filled with water or other applicable base fluid after step 720, the composition of the fluid is known. In other scenarios, the method may comprise the following sub step:

[0121] 731. This step indicates the optional step of determining the composition of the fluid presently held in the fluid loop. For the example of successive fills with different composition, determination of the composition may effectively be obtained from the preceding fill configuration, such as in step 705. In an example including priming of the system, as in step 720, including both the main line 11 and its components (including filters 18) and the recirculation line 50, the starting composition may in some examples be determined to have zero concentration. In various examples, it may nevertheless be noted that the step of initially determining the composition may be achieved using a sensor in the fluid loop, configured to measure a physical property indicative of the composition.

[0122] 732. Calculating an amount of concentrate to deliver based on the determined fluid composition. This may be based on a known or assessed fluid volume held in the fluid loop, as described in the previous description of the apparatus 10.

[0123] 733. Adding a volume of fluid, comprising the calculated amount of concentrate, to the fluid loop. This is typically achieved using the concentrate supply apparatus. In this step, the fluid is typically circulated until an even composition is obtained in the fluid loop.

[0124] As described above, the added volume of fluid may in some examples further comprise said base fluid. This may be relevant when the batch generation phase is carried out after a previous fill cycle (705) using a higher concentration of concentrate in the medical fluid, than the target composition to be used in the next fill cycle. Moreover, upon adding a volume of fluid, the method may further comprise purging a corresponding volume of fluid from the fluid loop at a connection downstream of the hold-up volume.

[0125] In certain examples, in particular when the volume of fluid, specifically liquid, held in the fluid loop is not known with sufficient accuracy to determine the amount of concentrate to add in order to obtain proper target composition of the medical fluid, the step of controlling 730 may be carried out iteratively. This has been described in detail with reference to the apparatus 10 and is equally applicable to the method. This is particularly related to addition of an electrolyte concentrate EC to the fluid loop 60.

[0126] In some examples, controlling comprises a first stage of controlling delivery of an electrolyte concentrate EC in the fluid loop, and a second stage of controlling delivery of an osmotic agent (OA) concentrate and the electrolyte (E) concentrate in the fluid loop. This will be discussed further below with reference to some examples.

[0127] While the controlling 730 serves to obtain a target composition including a target E concentration and a target OA concentration in the base fluid, the first stage may in some examples involve controlling the apparatus to obtain a desired E concentration in the fluid loop 60, which may be higher than the target E concentration. In this context, the desired E concentration may be determined by considering a target volume VOAC OAC to later be added in the second stage, which will dilute the fluid and thus lower the E concentration to obtain the target E concentration. As will be described further below, the first stage may be iterative.

[0128] In the second step, the OA concentration of the OAC source may be known from a manufacturer specification or from a device concentration test with sufficient accuracy. After the step 730 has resulted in the temporary target composition of EC being obtained, OAC may be dosed volumetrically by the specific pump 221 with the target OAC volume VOAC based on i) the target OA concentration in the final medical fluid, ii) the volume of water + EC in the fluid loop, and the volume (corresponding to the added volume of OAC) to be expelled from the fluid loop 60. In one example, no further water or EC is thus added in this step. In an alternative example, the main pump 14 and the pump 211 of the EC subunit 210 are volumetrically controlled to maintain a steady concentration of EC in the fluid loop 60 in this step. The mixture is then recirculated and, as the conductivity is deemed stable (homogenous solution), the resulting conductivity is measured and checked against an expected conductivity associated with the target composition.

[0129] Step 734 indicates that, after the step of adding 733 (optionally including recirculating to obtain a homogenous composition in the fluid loop), the resulting fluid composition may be determined. This may be achieved using a sensor in the fluid loop, configured to measure a physical property indicative of the composition, as described with reference to the apparatus above.

[0130] Step 735 indicates that a check may be carried out to determine whether or not a further iteration is required to obtain the target composition. This specifically relates to the obtaining the desired concentration of EC. This step may include comparing the determined, present, fluid composition in the fluid loop with a threshold level. The threshold level may correspond to the target threshold, optionally with an acceptable tolerance for deviation. Where the determined composition does not meet the requirements of the fluid in the fluid loop based on the check, e.g., that the present composition does not qualify as the target composition, the method may return to step 732, as indicated.

[0131] The combined steps 732-735 may in some examples be carried out in one sequence to determine what total volume of concentrate, e.g., EC, that needs to be added to the enclosed water volume of the fluid loop to cause a certain conductivity response. In simpler terms, by adding a first amount of EC and detecting the resulting concentration, a repeated calculation in step 732, second iteration, may provide an indication of how much additional concentrate that is required to be added to obtain, or come closer to, the target composition.

[0132] When the determined composition is determined to meet the requirements of the fluid in the fluid loop serving as the medical fluid of the target composition, the method may proceed, wherein the generated medical fluid may be delivered to an intended recipient, such as e.g., a cycler, a patient, or a storage container.

[0133] Step 740, specifically, indicates that the method may proceed with an online generation phase, in which the medical fluid of the obtained target composition is produced and delivered to the fluid outlet for direct delivery to the recipient. This may involve, upon obtaining the target composition of the medical fluid in the fluid loop, fluidly disconnecting the recirculation line from the main line, and fluidly connecting said portion to the medical fluid outlet. Thus, the batch generation phase may precede an online generation phase, wherein the batch generation phase serves the purpose of taking care of hold-up volumes and thereby reducing fluid waste. The online generation phase is typically the primary fluid generation mode of the apparatus.

[0134] With reference to the foregoing, the proposed solution fulfils the objective of decreasing waste of medical fluid, such as PD fluid (and hence waste of PD concentrates). Various additional aspects and details related to the application of the proposed solution for generation of PD fluid will be described below with reference to examples. Where useful, reference will be made to features or aspects indicated in the drawings and described in the foregoing.

[0135] After a heat disinfection performed between APD treatments, the ultrafilter(s) 181, 183 (hereinafter also referred to as UF) and the entire fluid path of the main line 11 are filled with priming fluid, such as water. To avoid the need for flushing and rinsing the water out of primarily the ultrafilters 181, 183 with online produced PD fluid and thereby waste considerable volumes of concentrates, the proposed solution will in some examples involve using the priming fluid present in the main line 11 for mixing with further addition of EC and OAC for obtaining medical fluid. In this context, the priming fluid present in the main line 11 includes the hold-up volume, typically defined by the filter(s) 181, 182. The method can also be used to avoid UF flushing when the PD fluid target composition is changed between dwells (glucose profiling).

[0136] Based on the proposed solution, generation of the PD fluid can be divided into two main phases;

[0137] 1. Batch generation (also referred to as batch mixing) with priming fluid, or PD fluid from previous mixing process, present in the main line 11, such as in the UF(s) 181, 183, followed by;

[0138] 2. Online generation (or mixing) until a target volume has been delivered to a dialysis fluid administration device, a container, or patient.

[0139] The proposed solution is specifically related to the Batch mixing phase.

[0140] With reference to the foregoing and Figs 5 and 6, a recirculation path constituting a fluid loop 60 is formed, comprising a portion 53 of the main line 11 and the recirculation line 50. The portion 53 comprises the main pump 14, a main mixing line through the mixing chamber 16 and the ultrafilters 18. The recirculation line 50 connects to the portion 53 and provides fluid connectivity back to the connection point 52 in the main line, and subsequently to an inlet port of the main pump 14. The fluid loop 60 thus holds the fluid present in the lines 50, 53, mixing chamber 16, and the ultrafilter compartments (lumen and shell side) of the filter(s) 18. The concentrate supply arrangement 20 is further configured to deliver concentrates, specifically EC and OAC, with separately controllable pumps 211, 221. All pumps 14, 211, 221 are preferably volumetric pumps with a volumetric precision assessed to be sufficient to enable volumetric dosing with small enough dosing error.

[0141] The number of ultrafilters 18 (181, 183) may be one or more. The priming volume of each ultrafilter depends on the type and size of the ultrafilter. For example, the Baxter U9000 has a total priming volume of 435ml. The priming volume of the lines and mixing chamber is typically much lower than that of the ultrafilters.

[0142] The purpose of the batch mixing phase is to fill the total fluid loop 60 (recirculation path) volume with PD fluid of correct composition for delivery to the receiving device 3 and thereby establish a situation equal to if the ultrafilters had been flushed with PD fluid. The total fluid loop 60 volume may be said to define the volume of one batch, generated in the batch mixing phase.

[0143] It should be noted that the composition accuracy requirement of the batch mixing sequence may not be as high as the composition accuracy requirement for an entire fill batch since the produced batch volume will typically be significantly lesser than the subsequent online mixed fluid obtained during the online generation phase, which probably can be made with higher composition accuracy. In some examples, the composition obtained in the batch mixing phase thus corresponds to the target composition of the PD fluid to be obtained in a subsequent online generation phase. In this context, the batch mixing phase may be operated to obtain a composition which corresponds to the target composition to be obtained during subsequent online generation with a certain level of accuracy, such as within a predetermined composition error margin.

[0144] The proposed solution for generating a medical fluid may be a method set out in the apparatus 10 as described herein. In some examples, the method comprises various steps, of which different examples and various details are outlined in this disclosure. On a general level, the method may in some examples be defined by the steps of:

[0145] Generating, in a fluid loop comprising a portion of the main line and a recirculation line connected to the main line, a batch volume of the medical fluid of a first composition based on residual fluid held in at least said portion of the main line. Disconnecting the recirculation line.

[0146] Initiating online generation of the medical fluid in the fluid main line.

[0147] Delivering the medical fluid at an outlet point of the main line, including delivering of at least part of the batch volume followed by delivering the medical fluid generated online.

[0148] As indicated earlier, there are (at least) two starting point scenarios for the batch mixing phase:

[0149] A. System (i.e. the fluid-containing parts of at least the main line 11, and optionally also the recirculation line 50, of the apparatus 10) is primed with disinfection water from a previous heat disinfection. The water can be considered to be pure from a chemical perspective but can have a concentration of endotoxins resulting from inactivated bacteria that is unacceptable for PD fluid mixing.

[0150] B. System is primed with PD fluid from previous fill and the composition (2ndtarget composition) of the PD fluid intended for the next fill differs from that of the previous fill (1sttarget composition). This is typically a result of a change in the target osmotic agent (OA), such as glucose, concentration. There are two inter dwell composition change scenarios:

[0151] B.l. Contained fluid has higher OA concentration than requested for next delivery of medical fluid.

[0152] B.2. Contained fluid has lower OA concentration than requested for next delivery of medical fluid

[0153] The following provides various examples of a method starting from starting point A, i.e., a sequence if the system is primed with disinfection water.

[0154] A.l. Water flush of all mixing system lines and dead volumes (including ultrafilters). The purpose is to replace the water used for disinfection (with potential endotoxin content) with pure water. This may correspond to step 720.

[0155] A.2. Contained fluid test. The purpose is to determine what total volume of EC that needs to be added to the enclosed water volume to cause a certain conductivity response (e.g., from sensor 17). A partial of expected EC volume needed for the batch (to obtain the target composition) is calculated (732) and volumetrically fed (733) to the fluid loop 60 at the supply point 15 using pump 211 of subunit 210. The mixture is then recirculated in the fluid loop 60 and, as the conductivity is measured and (734) deemed stable (homogenous solution), the resulting conductivity is used to calculate (732 - 2nditeration) the residual EC volume to add based on the resulting conductivity change. A water volume equivalent to the added EC volumes may be expelled to drain, as described, to maintain volume / pressure in the internal volume. The expelled water volume in this step and anticipated mixture volume in next step (resulting from residual EC volume to add) should be taken into account when calculating the residual EC volume to add in next step. The fact that the sum of EC volumes to add is input to the calculation of the EC volumes to add indicates that the calculation process needs to be iterative, as already described with reference to Fig. 7.

[0156] A.3. Residual amount of EC addition (733 - 2nditeration) to reach correct electrolyte concentration is made in the fluid loop 60 at the supply point 15. The mixture is then recirculated and, as the conductivity is deemed stable (homogenous solution), the resulting conductivity is measured (734) and checked (735) against a target conductivity. As described above, this step may be carried out to reach a certain desired electrolyte concentration, which may be higher than the target electrolyte concentration, by considering later addition of a volume of OA. In this context, the target conductivity for the EC + water mixture is a function of the target glucose concentration in the final PD fluid. A step 2 mixture volume equivalent to the added EC volume may during this process be expelled to drain, e.g., using valve 195, to maintain system volume / pressure in the internal volume.

[0157] A.4. As an alternative to steps 2-3, the water volume contained in the fluid loop

[0158] 60 and E concentration (0 if primed with water) may be known with sufficient accuracy beforehand. Steps 2-3 may then be replaced with the present step in which EC is dosed volumetrically followed by recirculation homogenization and a conductivity check.

[0159] The E concentration can be measured during an online mixing phase wherein EC and water are proportioned with relative volumetric control of pumps 14 and 211, and whereafter the E concentration is determined based on the conductivity of the mixture.

[0160] When the E concentration is known, the volume contained in the recirculation loop can be tested. At a state when the recirculation loop is filled with pure water, a known volume of the EC can be added with the volumetric EC pump and, after recirculation of the mixture and conductivity measurement as the mixture has been mixed to homogeneity as assessed by conductivity variance, the volume contained in the recirculation loop can be calculated based on the measured conductivity, the known E concentration and the added EC volume.

[0161] A.5. Glucose dosing. It is in this step assumed that the glucose concentrate

[0162] (GC) concentration is known from a manufacturer specification or from a device concentration test with sufficient accuracy. The GC is dosed volumetrically by the pump 221 with a target GC volume based on the target glucose concentration in the final PD fluid, the volume of EC + water solution present in the recirculation loop from previous steps and the volume of EC + water solution that needs to be expelled to drain to make room for the added GC volume. The mixture is then recirculated and, as the conductivity is deemed stable (homogenous solution), the resulting conductivity is measured and checked against an expected conductivity.

[0163] The following provides various examples of a method related to sequences with inter dwell composition change. It is assumed that the composition (glucose concentration) and volume of the PD fluid contained in the recirculation loop are known with sufficient accuracy. This will typically be the case after a preceding dwell using online mixing with a controlled composition of the medical fluid, and filling the entire fluid loop 60 with that medical fluid.

[0164] Based on starting point B.l, i.e., a switch shall be made to higher glucose concentration sequence (2ndtarget composition) from previous online generation 705 (using 1sttarget composition). In other words, the system holds PD fluid of a 1stOA concentration, and the objective is to reuse it for generating / adjusting to a 2ndOA concentration.

[0165] B.1.1. Based on the composition (glucose concentration), volume of the PD fluid contained in the fluid loop 60, and the sum of concentrate volumes to add to obtain the new OA concentration (2ndOA concentration), additionally required volumes of EC and OAC to reach the new 2ndtarget composition with higher glucose concentration are calculated (732). The fact that the sum of concentrate volumes to add is input to the calculation of the concentrate volumes to add indicates that the calculation process needs to be iterative, as described with reference to Fig. 7.

[0166] B.1.2. Addition (733) of further required volumes of EC and OAC while a volume equal to the sum of those volumes (replacement volume) of initially present PD fluid is expelled to drain, e.g., using valve 195, to maintain system volume / pressure in the internal volume. B.1.3. The mixture is then recirculated and, as the conductivity is deemed stable (homogenous solution), the resulting conductivity is measured (734) and checked (735) against an expected conductivity.

[0167] Based on starting point B.2, i.e., a switch shall be made to lower glucose concentration sequence (2ndtarget composition) from previous online generation 705 (using 1sttarget composition). In other words, the system holds PD fluid of a 1stOA concentration, and the objective is to reuse it for generating / adjusting to a 2ndOA concentration.

[0168] B.2.1. Based on the composition (glucose concentration), volume of the PD fluid contained in the recirculation loop, and the sum of concentrate volumes to add to obtain the new OA concentration (2ndOA concentration), additionally required volumes of EC and water (obtained from the inlet 12 using the main pump 14 and optionally operating a valve (not shown)) to reach the new composition with lower glucose concentration are calculated (732). The fact that the sum of EC and water volumes to add is input to the calculation of the EC and water volumes to add indicates that the calculation process needs to be iterative.

[0169] B.2.2. Addition (733) of further required volumes of EC and water while a volume equal to the sum of those volumes (replacement volume) of initially present PD fluid is expelled to drain, e.g., using valve 195, to maintain system volume / pressure in the internal volume.

[0170] B.2.3. The mixture is then recirculated and, as the conductivity is deemed stable (homogenous solution), the resulting conductivity is measured (734) and checked (735) against an expected conductivity.

[0171] During the online generation phase, or online mixing phase, the main pump 14 determines the main flow as it pumps the sum of the water and the concentrates. EC and GC are dosed with respective pumps 211, 221. Pump speed ratios of pumps 211 and 221 in relation to the main pump 14 determined during an initial online mixing phase may be used while running those pumps in open loop. It is anticipated that the composition control accuracy is higher with such online mixing than for the batch mixing described in the foregoing.

[0172] In a sequence of switching to and operating online generation of the medical fluid, the composition of the PD fluid generated in the batch mixing process described above, now contained in the fluid loop 60 including the ultrafilters, is assumed to be in accordance with the target PD fluid composition for the next dwell up to a certain accuracy requirement. This sequence may comprise the following steps:

[0173] 1. Fluidly disconnecting the recirculation line 50 from the main line 11, e.g., by operating valve 191, and fluidly connecting said portion 53 to the medical fluid outlet 13, e.g., by operating valve 192.

[0174] 2. Start of online mixing with pump speed settings based on previously established knowledge of concentration of E in EC, concentration of OA in OAC, and stroke volume ratios of main pump 14, EC pump 211 and OAC pump 221.

[0175] 3. Online mixing delivery to a dialysis fluid administration device or patient until target (fill) volume has been reached.

[0176] Various aspects of the proposed solution have been outlined in the foregoing, both related to the apparatus 10 and the method. In this context, it may be noted that the proposed solution is not limited to hold-up volumes caused by ultrafilter priming volumes but could be used to mitigate the negative effects of hold-up volumes caused by any component used for whatever reason. It may further be mentioned that EC and water proportioning with relative volumetric control can be achieved if the stroke volume ratio between the EC pump 211 and the main pump 14 can be determined. A way to determine this is to calibrate the pumps against each other. If both pumps are run with a closed volume in between (e.g. tubing and possibly a compliance increasing component such as a chamber containing air), the speed ratio between the pumps as they are controlled to maintain a pressure measured between the pumps to be constant (meaning that they are pumping at the same flow rate) is the inverse of their stroke volume ratio, and their stroke volume ratio can hence be determined. It shall also be noted that the recirculation line 50 may be accomplished in several ways, for example by using an existing heat disinfection path (possibly comprising parts of a dialysis fluid administration device fluidly connected to the mixing device) or by adding a dedicated mixing recirculation path.

Claims

35CLAIMS1. An apparatus (10) configured to generate a medical fluid, said apparatus comprising: a fluid main line (11) extending from a base fluid inlet point (12) to a medical fluid outlet point (13); a fluid pump (14) configured to pump fluid in the main line; a concentrate supply arrangement (20) fluidly connected at a supply point (15) on the main line; and a control system (20) configured to operate the apparatus in an online generation phase comprising to control the concentrate supply arrangement to continuously or continually deliver at least one concentrate at the supply point for mixing with the base fluid in the main line to form the medical fluid with a target composition to be delivered at the medical fluid outlet point; the apparatus further comprising a fluidly connectable recirculation line (50) configured to form a fluid loop together with a portion of the main line, which portion comprises the fluid pump, the supply point, and a hold-up volume in the main line downstream of the supply point; wherein the control system is configured to operate the apparatus in a batch generation phase comprising to control the concentrate supply arrangement to deliver the concentrate at the supply point based on a determined fluid composition of the fluid in the fluid loop, to form a medical fluid with a target composition in the fluid loop.

2. The apparatus of claim 1, wherein the control system is configured to control the concentrate supply arrangement based on a sensed property indicative of the fluid composition in the fluid loop.

3. The apparatus of claim 2, wherein the control system comprises a sensor (17) arranged in the fluid loop, configured to sense said property.

4. The apparatus of claim 3, wherein said sensor is arranged in said portion.

365. The apparatus of any preceding claim, further comprising a mixing chamber (16) arranged in said portion.

6. The apparatus of any preceding claim, wherein the hold-up volume is at least partially defined by one or more filter chambers (182, 184) in said portion of the main line.

7. The apparatus of any preceding claim, further comprising a valve arrangement (19), wherein the control system is configured to control the valve system in the batch generation phase to obtain: fluid connection of the recirculation line to the main line, and fluid disconnection of said portion from the medical fluid outlet.

8. The apparatus of claim 7, wherein, upon obtaining the target composition of the medical fluid, the control system is configured to control the valve system to obtain: fluid disconnection of the recirculation line from to the main line, and fluid connection of said portion to the medical fluid outlet.

9. The apparatus of any preceding of claim, wherein, in the batch generation phase, the control system is configured to: calculate an amount of concentrate to deliver based on the determined fluid composition; add, using at least the concentrate supply arrangement, a volume of fluid comprising the calculated amount of concentrate, to the fluid loop.

10. The apparatus of any of claims 1-8, wherein, in the batch generation phase, the control system is configured to iteratively: calculate an amount of concentrate to deliver based on the determined fluid composition; add, using at least the concentrate supply arrangement, a volume of fluid, comprising the calculated amount of concentrate, to the fluid loop; to achieve said target composition.

11. The apparatus of claim 9 or 10, wherein the added volume of fluid further comprises said base fluid.

12. The apparatus of any of claims 9-11, wherein the control system is configured to: purge a corresponding volume of fluid from the fluid loop at a connection downstream of the hold-up volume.

13. The apparatus of any of claims 9-12, wherein the control system is configured to calculate the amount based on a determined fluid volume present in the fluid loop.

14. The apparatus of any preceding claim, wherein the concentrate supply arrangement comprises: a first subunit (210) configured to supply a first concentrate including an electrolyte, and a second subunit (220) configured to supply a second concentrate including an osmotic agent, wherein the fluid composition is determined based on sensed electrical conductivity of the fluid in the fluid loop.

15. The apparatus of claim 14, wherein each subunit comprises a volumetric pump (211, 221), configured to deliver the respective concentrate.

16. A method for generating a medical fluid comprising a mixture of a base fluid and at least one concentrate in an apparatus usable for online generation of medical fluid in a fluid main line extending from a base fluid inlet point to a medical fluid outlet point, said method includes operating a batch generation phase comprising: connecting (710) a recirculation line to a portion of the main line, said portion comprising a fluid pump, a supply point of concentrate delivery to the main line, and a hold-up volume downstream the supply point, wherein a fluid loop comprising said portion and the recirculation line is obtained;controlling (730), based on a determined fluid composition in the fluid loop, delivery of the concentrate at the supply point to form the medical fluid with a target composition in the fluid loop.

17. The method of claim 16, further comprising an initial step of: priming (720) at least the main line with the base fluid.

18. The method of claim 16 or 17, wherein concentrate delivery is controlled based on a sensed property indicative of the fluid composition in the fluid loop.

19. The method of any of claims 16-18, wherein the hold-up volume is at least partially defined by a filter chamber in the main line.

20. The method of any of claims 16-19, wherein connecting comprises: fluidly connecting the recirculation line to the main line, and fluidly disconnecting said portion from the medical fluid outlet.

21. The method of claim 20, further comprising, upon obtaining the target composition of the medical fluid in the fluid loop: fluidly disconnecting the recirculation line from the main line, and fluidly connecting said portion to the medical fluid outlet.

22. The method of any of claims 16-21, wherein controlling comprises: calculating (732) an amount of concentrate to deliver based on the determined fluid composition; adding (733) a volume of fluid, comprising the calculated amount of concentrate, to the fluid loop.

23. The method of any of claims 16-21, wherein controlling comprises iteratively: calculating (732) the amount of concentrate to deliver based on the determined fluid composition; adding (733) a volume of fluid, comprising the calculated amount of concentrate, to the fluid loop;to achieve said target composition.

24. The method of claim 22 or 23, wherein the added volume of fluid further comprises said base fluid.

25. The method of any of claims 22-24, further comprising: purging a corresponding volume of fluid from the fluid loop at a connection downstream of the hold-up volume.

26. The method of any of claims 22-25, wherein the calculating is based on a determined fluid volume present in the fluid loop27. The method of any of claims 16-26, wherein controlling comprises: a first stage of controlling delivery of an electrolyte concentrate in the fluid loop, and a second stage of controlling delivery of an osmotic agent concentrate and the electrolyte concentrate in the fluid loop.

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