Dialysis fluid generation apparatus

Abstract

A dialysis fluid generation apparatus is provided with a fluid circuit including a main fluid line having an inlet for receiving water, a pump to pump fluid in the main fluid line, a plurality of valves configurable to define different fluid paths for the fluid inside the fluid circuit. A control unit is configured to execute a dialysis fluid preparation procedure comprising a first a second concentrate mixing sequence, wherein, during execution of the first concentrate mixing sequence, the control unit is configured to control a first dosing pump flow rate based on the received signals relating to the property of the mixture of water and first concentrate in the main fluid line and, during execution of the second concentrate mixing sequence, to control a second dosing pump flow rate based on the received signals relating to the property of the mixture of water, first concentrate and second concentrate in the main fluid line.

Description

TITLEMEDICAL FLUID GENERATION APPARATUSBACKGROUND

[0001] The present disclosure relates generally to a medical fluid generation apparatus, in particular for dialysis fluid treatments. In more detail, embodiments of the present disclosure relate to online preparation of medical fluid such as dialysis fluid for peritoneal dialysis or haemodialysis. 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.

[0002] Due to various causes, a person’s renal system may fail. Renal failure produces several physiological derangements. 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.

[0003] Reduced kidney function and, above all, kidney failure is treated with dialysis. Dialysis removes waste, toxins, and excess water from the body that normal functioning kidneys would otherwise remove. Dialysis treatment for replacement of kidney functions is critical to many people because the treatment is lifesaving.

[0004] 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 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.

[0005] 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 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.

[0006] Hemodiafiltration (“HD F”) is a treatment modality that combines convective and diffusive clearances. HDF uses dialysis 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.

[0007] Another type of kidney failure therapy is peritoneal dialysis (“PD”), which infuses 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 waterpass 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. PD fluids are typically prepared in a factory and shipped to the patient’s home in ready-to-use bags.

[0008] 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.

[0009] 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 may be manually emptied at some point during the day.

[0010] As indicated, the dialysis machines, either for haemodialysis or for peritoneal dialysis, usually requires an important amount of fresh dialysis liquid to be used during the respective therapies. Handling a huge number of relatively heavy bags (e.g., 5 / 8 liter bags) storing ready to use dialysis fluid is sometimes problematic and requires efforts and storing location. This is particularly, but not exclusively, relevant in case of home dialysis, wherein it is the patient or his / her family members who has to handle the fluid reservoirs. A need exists accordingly to provide an improved apparatus capable of producing andpossibly temporary storing a certain amount of medical fluid starting from fresh (pre-treated) water and proper concentrates.

[0011] Some prior documents disclose preparation of dialysis fluid from dry concentrates, mainly for HD. Also, the general concept of mixing PD-fluid from concentrates is known.

[0012] EP2767296 discloses a dialysis fluid preparation apparatus with a water feed passage, a first fluid passage to feed a first concentrate fluid, a second fluid passage to feed a second concentrate fluid, and concentration measurement sensors. The apparatus mixes the purified water, the first fluid, and the second fluid in predetermined proportions respectively to prepare a dialysis fluid, and measures the concentration of the prepared dialysis fluid by the concentration measurement sensors. Before preparation of the dialysis fluid, in a state in which the dialysis fluid and the first fluid are not flowed to the water feed passage, the second fluid is fed from the second fluid passage to the water feed passage so that only the second fluid is flowed to the water feed passage, the electric conductivity of the second fluid is measured by the detection units of the concentration measurement sensors, and the measured electric conductivity of the second fluid is compared with a previously set value. The accuracy of the three concentration measurement sensors is consequently diagnosed.

[0013] WO2017 / 176701 is directed to a system for generating peritoneal dialysate and using the peritoneal dialysate with an integrated cycler. The system uses a water purification unit, a sterilization module, and concentrates to prepare peritoneal dialysate from source water and infuse the prepared peritoneal dialysate into a patient with the integrated cycler. Dialysate storage containers are provided for storage of the peritoneal dialysate prior to use.

[0014] EP1312386A2 discloses a bag with dry concentrate, for example an acid concentrate; the system is intended for preparation of dialysis fluid for blood dialysis. The bag holds a diluted concentrate solution and has two separate ports. Water is pumped into the bag via one port, whereby the dry concentrate is dissolved. After the bag is filled with a certain amount of water, the diluted solution is circulated to ensure it is dissolved. Thereafter the fluid may be pumped to a dialysis apparatus for use.

[0015] From EP2305331A1 it is known to dissolve powder in two different containers and circulate it in a circulation line. When the powder is dissolved, it is dosed with flow chambers and the conductivity is checked.

[0016] US2020 / 0390956A1 describes a PD machine for preparing PD-solution from RO water.

[0017] EP3222303B1 illustrates mixing of powder with water and mixing a dialysis solution from drug A and drug B into a first container, recirculating, and delivering it to a second container from where it is sent to a dialysis device for use.

[0018] US2019262522A1 disclose to mix osmotic agent, electrolyte, and water in a mixing container for mixing liquid concentrates into PD fluid.SUMMARY

[0019] The present disclosure sets forth apparatus and methods for producing a medical fluid, particularly a dialysis fluid, such as peritoneal dialysis (“PD”) fluid and hemodialysis (“HD”) fluids. 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 hemofiltration (“HF”) and hemodiafiltration (“HDF”), lactated ringers and the like. The medical fluid generation apparatus receives water purified by a water purification apparatus (e.g., a reverse osmosis device) or, alternatively, receives tap water that is firstly purified inside the apparatus and then used to prepare a suitable dialysis fluid. In a PD fluid example, the pure water receives PD concentrates when making PD fluid and the fluid is then mixed in a mixing chamber before delivery to a PD cycler; usually two PD concentrates are used including electrolytes and an osmotic agent (such as glucose). In a HD fluid example, pure water is mixed with one or two concentrates, such as an A concentrate and a B concentrate, including a buffer concentrate (e.g., bicarbonate, acetate or lactate) and including an electrolyte concentrate with sodium, calcium, magnesium and potassium ions, and is delivered to a haemodialysis apparatus or stored in a mixing container or bag.

[0020] In light of the disclosure set forth herein, and without limiting the disclosure in any way, in a 1stindependent aspect, which may be combined with any other aspect or portion thereof described herein, a medical fluid generation apparatus (1) comprises: a fluid circuit (2) including a main fluid line (3) developing between an inlet point (4) for receiving water and an outlet point (5) connectable to a treatment medical device, a main pump (6) located on the main fluid line (3) to pump fluid at least in the main fluid line (3), wherein the fluid circuit (2) further includes: o a first concentrate access (7) fluidly connectable to a port (8) of a first concentrate container (9) containing a first concentrate (F), o a first dosing line (10) putting in fluid communication the first concentrate access (7) and the main fluid line (3) at a first injection point (j 1) located between the inlet point (4) and the outlet point (5), o a second concentrate access (12) fluidly connectable to a port (13) of a second concentrate container (14) containing a second concentrate (S), o a second dosing line (15) putting in fluid communication the second concentrate access (12) and the main fluid line (3) at a second injection point (]2) located between the inlet point (4) and the outlet point (5); o a mixing chamber (17) placed on the main fluid line (3) and located downstream the first injection point (j1) and the second injection point (]2) and upstream the outlet point (5), the mixing chamber (17) comprising a mixing chamber inlet (17a) configured to receive fluid fromthe main fluid line (3) and a mixing chamber outlet (17b) configured to release fluid to the main fluid line (3), a first dosing pump (11) configured to pump fluid in the first dosing line (10), a second dosing pump (16) configured to pump fluid in the second dosing line (15), a plurality of valves (V1 , .... Vn) located on the fluid circuit (2) and configurable to define different fluid paths for the fluid inside the fluid circuit (2), at least one sensor (18; 31; 54) configured to measure a property of the fluid flowing in the main fluid line (3), wherein the at least one sensor (18; 31; 54) is located downstream the first injection point (j1), the second injection point (j2) and the mixing chamber (17), a control unit (19) configured to operate the plurality of valves to define the different fluid paths inside the fluid circuit (2), wherein the control unit (19) is configured to execute a medical fluid preparation procedure comprising a first concentrate mixing sequence and a second concentrate mixing sequence, wherein, during execution of the first concentrate mixing sequence, the control unit (19) is configured to:• operate the main pump (6) to pump fluid in the main fluid line (3);• operate the first dosing pump (11) to inject first concentrate from the first concentrate container (9) into the main fluid line (3) at the first injection point (j 1 );• receive signals from the at least one sensor (18; 31; 54) relating to the property of the mixture of water and first concentrate in the main fluid line (3);• control a first dosing pump flow rate and / or a main pump flow rate or a ratio thereof based on the received signals relating to the property of the mixture of water and first concentrate in the main fluid line (3); wherein, during execution of the second concentrate mixing sequence, the control unit (19) is further configured to:• operate the second dosing pump (16) to inject second concentrate from the second concentrate container (14) into the main fluid line (3) at the second injection point (j2);• receive signals from the at least one sensor (18; 31 ; 54) relating to the property of the mixture of water, first concentrate, and second concentrate in the main fluid line (3);• control a second dosing pump flow rate and / or a ratio between the second dosing pump flow rate and the main pump flow rate and / or a ratio between the second dosing pump flow rate and the first dosing pump flow rate based on the received signals relating to the property of the mixture of water, first concentrate, and second concentrate in the main fluid line (3).

[0021] In a further independent aspect a method of generating a medical fluid is provided comprising: providing a medical fluid generation apparatus (1) comprising:o a fluid circuit (2) including a main fluid line (3) developing between an inlet point (4) for receiving water and an outlet point (5) connectable to a treatment medical device, o a main pump (6) located on the main fluid line (3) to pump fluid at least in the main fluid line (3), wherein the fluid circuit (2) further includes:■ a first concentrate access (7) fluidly connectable to a port (8) of a first concentrate container (9) containing a first concentrate (F),■ a first dosing line (10) putting in fluid communication the first concentrate access (7) and the main fluid line (3) at a first injection point (j1) located between the inlet point (4) and the outlet point (5),■ a second concentrate access (12) fluidly connectable to a port (13) of a second concentrate container (14) containing a second concentrate (S),■ a second dosing line (15) putting in fluid communication the second concentrate access (12) and the main fluid line (3) at a second injection point (j2) located between the inlet point (4) and the outlet point (5);■ a mixing chamber (17) placed on the main fluid line (3) and located downstream the first injection point (j1) and the second injection point (j2) and upstream the outlet point (5), the mixing chamber (17) comprising a mixing chamber inlet (17a) configured to receive fluid from the main fluid line (3) and a mixing chamber outlet (17b) configured to release fluid to the main fluid line (3), o a first dosing pump (11) configured to pump fluid in the first dosing line (10), o a second dosing pump (16) configured to pump fluid in the second dosing line (15), o a plurality of valves (V1, .... Vn) located on the fluid circuit (2) and configurable to define different fluid paths for the fluid inside the fluid circuit (2), o at least one sensor (18; 31 ; 54) configured to measure a property of the fluid flowing in the main fluid line (3), wherein the at least one sensor (18; 31 ; 54) is located downstream the first injection point (j1), the second injection point (j2) and the mixing chamber (17), o a control unit (19) configured to operate the plurality of valves to define the different fluid paths inside the fluid circuit (2), executing a medical fluid preparation procedure comprising a first concentrate mixing sequence and a second concentrate mixing sequence, wherein, during execution of the first concentrate mixing sequence, the method further comprises:• operating the main pump (6) to pump fluid in the main fluid line (3);• operating the first dosing pump (11) to inject first concentrate from the first concentrate container (9) into the main fluid line (3) at the first injection point (j1);• obtaining signals from the at least one sensor (18; 31; 54) relating to the property of the mixture of water and first concentrate in the main fluid line (3);• controlling a first dosing pump flow rate and / or a main pump flow rate or a ratio thereof based on the received signals relating to the property of the mixture of water and first concentrate in the main fluid line (3); wherein, during execution of the second concentrate mixing sequence, the method further comprises:• operating the second dosing pump (16) to inject second concentrate from the second concentrate container (14) into the main fluid line (3) at the second injection point (j2);• obtaining signals from the at least one sensor (18; 31; 54) relating to the property of the mixture of water, first concentrate, and second concentrate in the main fluid line (3);• controlling a second dosing pump flow rate and / or a ratio between the second dosing pump flow rate and the main pump flow rate and / or a ratio between the second dosing pump flow rate and the first dosing pump flow rate based on the received signals relating to the property of the mixture of water, first concentrate, and second concentrate in the main fluid line (3).

[0022] In a further independent aspect a method (1000) of generating a medical fluid is provided comprising: providing (1001) a medical fluid generation apparatus (1) comprising: o a fluid circuit (2) for receiving water; o a main pump (6) located on the fluid circuit (2), o a plurality of valves (V1, .... Vn) located on the fluid circuit (2) and configurable to define different fluid paths for the fluid inside the fluid circuit (2), o at least one sensor (18; 31 ; 54) configured to measure a property of the fluid flowing in the fluid circuit (2), o a control unit (19) configured to control the apparatus (1) including to operate the plurality of valves to define the different fluid paths inside the fluid circuit (2), executing (1002) a medical fluid preparation procedure comprising a first concentrate mixing sequence (1003) and a second concentrate mixing sequence (1004), wherein, during execution of the first concentrate mixing sequence (1003), the method comprises:• operating (1005) a main pump (6) to pump fluid in a main fluid line (3) of the fluid circuit (2);• operating (1006) a first dosing pump (11) to inject a first concentrate from a first concentrate container (9) into the main fluid line (3) at a first injection point (j1) where the first concentrate mixes with water;• obtaining (1007) signals from the at least one sensor (18; 31 ; 54) relating to the property of the mixture of water and first concentrate in the main fluid line (3);• controlling (1008) a first dosing pump flow rate and / or a main pump flow rate or a ratio thereof based on the received signals relating to the property of the mixture of water and first concentrate in the main fluid line (3); wherein, during execution of the second concentrate mixing sequence (1004), the method further comprises:• operating (1011) a second dosing pump (16) to inject a second concentrate from a second concentrate container (14) into the main fluid line (3) at a second injection point (]2) where the second concentrate mixes with the first concentrate and water;• obtaining (1012) signals from the at least one sensor (18; 31 ; 54) relating to the property of the mixture of water, first concentrate, and second concentrate in the main fluid line (3);• controlling (1013) a second dosing pump flow rate and / or a ratio between the second dosing pump flow rate and the main pump flow rate and / or a ratio between the second dosing pump flow rate and the first dosing pump flow rate based on the received signals relating to the property of the mixture of water, first concentrate, and second concentrate in the main fluid line (3).

[0023] In the above methods the various method steps are executed by the control unit (19) of the apparatus. In the following aspects the steps executed by the control unit (19) are also intended as method steps of the independent method aspect.

[0024] The plurality of valves are identified in the drawings by letters V or V...’ and a corresponding number, e.g., V6, V6’, V23, etc. For convenience, when referring generally to the plurality of valves, the designation ‘V,...,Vri is used.

[0025] In a 2ndaspect according to the previous aspect, the control unit (19) is configured to operate the second dosing pump (16) subsequent to execution of the first concentrate mixing sequence. In otherwords, the first concentrate mixing sequence is run before the second concentrate mixing sequence.

[0026] In a 3rdaspect according to any one of the previous aspects, said property of the fluid is chosen in the group consisting of a conductivity of the fluid, a concentration of a substance in the fluid, a concentration dependent physical property, such as sound velocity, viscosity, density, a temperature of the fluid, and an optical property of the fluid and combinations thereof.In a non-limiting approach, the fluid property to be determined is a concentration property that is determined by means a conductivity sensor.

[0027] In a 4thaspect according to any one of the previous aspects, the at least one sensor (18; 31; 54) comprises at least one of a conductivity sensor, a concentration sensor, a temperature sensor, an optical sensor, a viscosity sensor, a density sensor, and a sound sensor.

[0028] In an embodiment, the at least one sensor is a conductivity sensor; in another embodiment, it may be a concentration sensor tied to a substance in the concentrate to be controlled, for example a glucose sensor if the concentrate would contain glucose.

[0029] In a 5th aspect according to any one of the previous aspects, during execution of the first concentrate mixing sequence, the control unit (19) is configured to:• obtain a first property-of-the-flu id target for a mixture of water and first concentrate; wherein controlling the first dosing pump flow rate and / or the main pump flow rate or the ratio thereof comprises:• control a first dosing pump flow rate and / or a main pump flow rate to bring the property of the mixture of water and first concentrate in the main fluid line (3) towards the first property-of-the- fluid target;• measure the property of the mixture of water and first concentrate in the main fluid line (3);• determine (1009) the first dosing pump flow rate and the main pump flow rate or a ratio thereof when the measured property fulfills a first criteria of having reached the first property-of-the-fl uid target.

[0030] In a 6thaspect according to the previous aspect, after determining the first dosing pump flow rate and the main pump flow rate or the ratio thereof, the control unit (19) is further configured to:• operate (1010) the first dosing pump flow rate and the main pump flow rate at the determined first dosing pump flow rate and main pump flow rate or at the determined ratio to allow the property of the mixture of water and first concentrate to stabilize;• calculate a statistical property, e.g., a filtered mean, of said property of the mixture of water and first concentrate;• store the statistical property as a reached first property for the mixture of water and first concentrate.

[0031] In a 7thaspect according to the previous two aspects, said first criteria comprises verifying that the mixture of water and first concentrate is within a predefined range of the first property-of- the-fluid target, such as within 2%, in particular within 0.5% and for example within 0.2%.

[0032] In an 8thaspect, according to any one of aspects 5 to 7, the control unit (19) is configured to:• calculate the first property-of-the-fluid target for a mixture of water and first concentrate based on nominal concentrations of one or more solutes in the first concentrate (F) and optionally on conductivity equations for each of said one or more solutes in the first concentrate (F); or• receive the first property-of-the-fluid target as external input or as stored data, optionally after experimentally determining it.

[0033] In a 9thaspect according to any one of the previous aspects, during execution of the first concentrate mixing sequence, the control unit (19) is configured to:• keep the second dosing pump (16) inactive with no flow in the second dosing line (15).

[0034] In a 10thaspect according to any one of the previous aspects, during execution of the first concentrate mixing sequence, the control unit (19) is configured to:• control the first dosing pump flow rate, particularly based on a property feedback controller, and• keep the main pump flow rate substantially constant.As this aspect indicates, the main pump flow rate does not change, it is set to a predetermined (fixed) flow rate at the start of the first concentrate mixing sequence. Only the flow rate of the primary dosing pump is controlled (flow rate is adjusted) to achieve the target concentration of the water and first concentrate mixture. The two pumps are then “locked” together and a ratio is established. The main flow pump can now vary while the ratio is still held at the same determined value, i.e., the concentrate pump varies together with the main flow pump.The used wording main pump flow rate 'substantially constant’ means that the main pump flow rate is constant within a predetermined margin that is at the minimum linked to the accuracy of the pump (inherent in the way the main fluid pump works). The predetermined margin may be greater than the pump accuracy to take into account minor changes of the main pump flow rate during dosing that still allows the measured property of the medical fluid to meet the property-of-the-fluid target.

[0035] In an 11 aspect according to any one of the previous aspects, the at least one sensor (18; 31; 54) comprises a first sensor (18) placed on the main fluid line (3).

[0036] In a 12thaspect according to any one of the previous aspects, the control unit (19) is configured to control the plurality of valves to define a first mixing flow path comprising:• an initial portion (48) of the main fluid line (3) including the first injection point (j1), the second injection point (]2) and the mixing chamber (17) and a diverting point (47); and• an evacuation line (40) fluidly connected to the diverting point (47) and routing the fluid towards a drain (27), wherein the first mixing flow path is defined at least during execution of the first concentrate mixing sequence and / or the second concentrate mixing sequence.

[0037] In a 13thaspect according to the previous aspect, the at least one sensor (18; 31 ; 54) comprises a second sensor (31) located on the evacuation line (40) to measure the property of the fluid flowing in the initial portion of the main fluid line (3).

[0038] In a 14thaspect according to any one of the previous two aspects, when the first mixing flow path is defined, a diverting valve (V13) of the plurality of valves is configured to allow the fluid to flow from the initial portion (48) of the main fluid line (3) to the evacuation line (40).

[0039] In a 15thaspect according to any one the previous three aspects and aspect 11 , the first sensor (18) is located in the initial portion (48) of the main fluid line (3) upstream of the diverting point (47).

[0040] In a 16thaspect according to any one of the previous four aspects, the main fluid line (3) further comprises a terminal portion (49) extending from the diverting point (47) to the outlet point (5), during execution of the first concentrate mixing sequence no fluid is flowing in the terminal portion (49).The terminal portion 49 of the main fluid line 3 comprises one or more of an air intake point where an air intake line 45 is connected to the main fluid line 3, a filter 24, and a second filter 26.

[0041] In a 17thaspect according to any one of the previous five aspects, the plurality of valves controlled by the control unit (19) to define the first mixing flow path comprises one or more of:• a water inlet valve (V3) located on the initial portion (48) of the main fluid line (3), set in a configuration that allows water to flow along the initial portion (48);• a recirculation valve (V15) located on the initial portion (48) of the main fluid line (3), set in a configuration that allows water to flow along the initial portion (48);• a discharge valve (V6) downstream the mixing chamber (17) located on the initial portion (48) of the main fluid line (3), set in a configuration that allows water to flow along the initial portion (48);• a diverting valve (V13) located on the initial portion (48) of the main fluid line (3), set in a configuration that allows the fluid to flow from the initial portion (48) of the main fluid line (3) to the evacuation line (40), the diverting valve (V13) being set in a configuration that prevents the fluid to flow from the initial portion (48) to a terminal portion (49) of the main fluid line (3); and• a closure valve (V12) located on the evacuation line (40), set in a configuration that allows the fluid to flow through the evacuation line (40) towards a drain (27).In accordance with this aspect, the first mixing flow path will be a first divert-to-drain flow path, where the fluid is directed to the drain (27).

[0042] In an 18thaspect according to any one of the previous aspects, the control unit (19) is configured to control the plurality of valves to define a medical fluid delivery flow path comprising the main fluid path (3) from the inlet point (4) to the outlet point (5), during a medical fluid delivery phase, pure water flowing through the inlet point and towards the first injection point (j1 ), and a medical fluid, for example a dialysis treatment fluid, flowing out of the outlet point (5).

[0043] In a 19thaspect according to the previous aspect, the plurality of valves controlled by the control unit (19) to define the medical fluid delivery flow path comprises one or more of: a water inlet valve (V3) located on an initial portion (48) of the main fluid line (3), set in a configuration that allows water to flow along the initial portion (48); a recirculation valve (V15) located on the initial portion (48) of the main fluid line (3), set in a configuration that allows water to flow along the initial portion (48); a discharge valve (V6) downstream the mixing chamber (17) located on the initial portion (48) of the main fluid line (3), set in a configuration that allows water to flow along the initial portion (48); a diverting valve (V13) located on the initial portion (48) of the main fluid line (3), set in a configuration that allows water to flow from the initial portion (48) towards a terminal portion (49) of the main fluid line (3), in particular the diverting valve (V13) being set in a configuration that prevents the fluid to flow from the initial portion (48) of the main fluid line (3) to an evacuation line (40);an air intake valve (V4) located on the terminal portion (49) of the main fluid line (3), set in a configuration that allows water to flow along the terminal portion (49); a closure valve (V9) located on the terminal portion (49) of the main fluid line (3), set in a configuration that allows water to flow along the terminal portion (49); and a delivery valve (V8) located on the terminal portion (49) of the main fluid line (3), set in a configuration that allows water to flow along the terminal portion (49) to the outlet point (5).

[0044] In a 20thaspect according to any one of the previous aspects, during execution of the second concentrate mixing sequence, the control unit (19) is configured to:• obtain a second property-of-the-fluid target for a mixture of water, first concentrate, and second concentrate; wherein controlling second dosing pump flow rate and / or a ratio between the second dosing pump flow rate and the main pump flow rate and / or a ratio between the second dosing pump flow rate and the first dosing pump flow rate comprises:• change the second dosing pump flow rate and / or the main pump flow rate, keeping the ratio of the first dosing pump flow rate and the main pump flow rate constant, to bring the property of the mixture of water, first concentrate, and second concentrate in the main fluid line (3) towards the second property-of-the-fluid target;• measure the property of the mixture of water, first concentrate, and second concentrate in the main fluid line (3);• determine (1014) the second dosing pump flow rate or a ratio between the second dosing pump flow rate and the main pump flow rate or a ratio between the second dosing pump flow rate and first dosing pump flow rate when the measured property fulfills a second criteria of having reached the second conductivity target.

[0045] In a 21staspect according to the previous aspect, the second property-of-the-fluid target for a mixture of water, first concentrate, and second concentrate is lower than the first property-of-the-fluid target for a mixture of water and first concentrate.

[0046] In a 22ndaspect according to any one of the previous two aspects, the control unit (19) is configured to: calculate the second property-of-the-fluid target for the mixture of water, first concentrate, and second concentrate based on a target concentration for the mixture of water, first concentrate, and second concentrate of at least one substance in the second concentrate (S), in particular said substance being glucose; or receive the second property-of-the-fluid target as external input or as stored data, optionally after experimentally determining it.

[0047] In a 23rdaspect according to the previous aspect, the control unit (19) is configured to:calculate the second property-of-the-fluid target further based on a reached first property, being the first property-of-the-fluid target plus a control error.

[0048] In a 23rdbis aspect according to the previous aspect and aspect 6, the control error is a difference between the first property-of-the-fluid target and the reached first property achieved when controlling the first dosing pump (11) and the main pump (6) at the determined first dosing pump flow rate and main pump flow rate or the ratio thereof.

[0049] In a 24thaspect according to any one of the previous aspects, during execution of the second concentrate mixing sequence, the control unit (19) is configured to: control the second dosing pump (16) at an overdose flow rate to inject an overdose of the second concentrate (S) into the main fluid line (3); and subsequently measure the property of the mixture of water, first concentrate, and second concentrate in the main fluid line (3); reduce the overdose flow rate of the second dosing pump (16) based on the subsequently measured property of the mixture of water, first concentrate, and second concentrate.

[0050] In a 25thaspect according to the previous aspect, the control unit (19) is configured to: reduce the overdose flow rate of the second dosing pump (16) further based on a delta between the first property-of-the-fluid target and the second property-of-the-fluid target.

[0051] In a 26thaspect according to the previous aspect, the control unit (19) is configured to calculate a speed of the second dosing pump (16) based on the following formula:Target S responseLocked S pump speed = Overdose S pump speed ■ -Overdose S response wherein:• 'Locked S pump speed’ is the calculated speed of the second dosing pump (16);• 'Overdose S pump speed’ is a set speed of the second dosing pump (16) to generate the overdose flow rate;• 'Target S response’ is the delta between the reached first property-of-the-fluid and the second property- of-the-fluid target;• 'Overdose response’ is an actual delta between the reached first property-of-the-fluid and a measured property of the mixture of water, first concentrate, and second concentrate after the generation of the overdose flow rate.

[0052] In a 27thaspect according to any one of the previous aspects 1 to 23, during execution of the second concentrate mixing sequence, the control unit (19) is configured to:• control the second dosing pump flow rate particularly based on a property feedback controller, and• keep the main pump flow rate and the first dosing pump flow rate, or a ratio thereof, substantially constant.The main pump flow rate is kept constant within a predetermined margin.

[0053] In a 28thindependent aspect, which may be combined with any other of the previous and following aspects or portion thereof described herein, a medical fluid generation apparatus (1) comprises: a fluid circuit (2) including a main fluid line (3) developing between an inlet point (4) for receiving water and an outlet point (5) fluidly connectable to a medical device for treatment, a main pump (6) active on the main fluid line (3) to pump fluid at least in the main fluid line (3), wherein the fluid circuit (2) further includes: o a first concentrate access (7) fluidly connectable to a port (8) of a first concentrate container (9) containing a first concentrate (F), o a first dosing line (10) putting in fluid communication the first concentrate access (7) and the main fluid line (3) at a first injection point (j1) located between the inlet point (4) and the outlet point (5), o a second concentrate access (12) fluidly connectable to a port (13) of a second concentrate container (14) containing a second concentrate (S), o a second dosing line (15) putting in fluid communication the second concentrate access (12) and the main fluid line (3) at a second injection point (j2) located between the inlet point (4) and the outlet point (5); o a mixing chamber (17) placed on the main fluid line (3) and located downstream the first injection point (j1) and the second injection point (]2) and upstream the outlet point (5), the mixing chamber (17) comprising a mixing chamber inlet (17a) configured to receive fluid from the main fluid line (3) and a mixing chamber outlet (17b) configured to release fluid to the main fluid line (3), a first dosing pump (11) configured to circulate fluid in the first dosing line (10), a second dosing pump (16) active to circulate fluid in the second dosing line (15), a plurality of valves (V1 to Vn) active on the fluid circuit (2) and configurable to define different fluid paths for the fluid inside the fluid circuit (2), a control unit (19) configured to operate the plurality of valves to define the different fluid paths inside the fluid circuit (2) and to operate the main pump (6), the first dosing pump (11) and the second dosing pump (16) to move fluid in the different fluid paths.

[0054] In a 29thaspect according to the previous aspect, the apparatus further comprises at least one sensor (18; 31 ; 54) configured to measure a property of the fluid flowing in the main fluid line (3), the control unit (19) being configured to receive a signal from the at least one sensor (18; 31 ; 54), whereinthe at least one sensor (18; 31; 54) is located downstream the first injection point (j 1 ), the second injection point (j2) and the mixing chamber (17).

[0055] In a 30thaspect according to the previous aspect, the main pump (6) is located upstream of the at least one sensor (18; 31; 54) along a fluid flow direction.

[0056] In a 31staspect according to any one of the previous aspects, the main pump (6) is located downstream the first injection point (j1), the second injection point (]2) and the mixing chamber (17).

[0057] In a 32ndaspect according to any one of the previous aspects 1 to 30, the main pump (6) is located downstream the first injection point (j1) and the second injection point (]2) and upstream the mixing chamber (17).

[0058] In a 33rdaspect according to any one of the previous aspects, the main pump (6) is located upstream the first injection point (j1), the second injection point (]2) and the mixing chamber (17).

[0059] In a 34thaspect according to any one of the previous aspects 1 to 32, the main pump (6) is located downstream the first injection point (j1) and upstream the second injection point (j2) and the mixing chamber (17).

[0060] In a 35thaspect according to any one of the previous aspects, the fluid circuit (2) comprises an evacuation line (40) fluidly connecting the main fluid line (3) to a drain (27), wherein the plurality of valves comprises a diverting valve (V13) to selectively prevent or allow fluid flow in the evacuation line (40).

[0061] The evacuation line (40) and diverting valve (V13) are used to direct the mixed solution to drain (27) during composition / temperature stabilization and in any fault condition of the apparatus.

[0062] In a 36thaspect according to the previous aspect, the diverting valve (V13) is located on the main fluid line (3), the control unit (19) being configured to switch the diverting valve (V13) from a first operating condition permitting a fluid flow along the main fluid line (3) and preventing a fluid flow along the evacuation line (40), to a second operating condition permitting a fluid flow from the main fluid line (3) upstream of the diverting valve to and along the evacuation line (40) and preventing a fluid flow from upstream of the diverting valve to a terminal portion (49) of the main fluid line (3).

[0063] In a 37thaspect according to any one of the previous two aspects, the plurality of valves further comprises a closure valve (V12) located on the evacuation line (40) to selectively close a fluid communication to the drain (27).

[0064] In a 38thaspect according to any one of the previous aspects, said at least one sensor (18; 31 ; 54) comprises a first sensor (18) located on the main fluid line (3), optionally the first sensor (18) being a conductivity sensor.

[0065] In a 39thaspect according to the previous aspect, the apparatus further comprises a temperature sensor (T3) associated to the first sensor (18) to measure a temperature of a fluid sensed by the first sensor (18) and allow for temperature compensation of the property of the fluid flowing in the main fluid line (3).

[0066] In a 40thaspect according to any one of the previous aspects, said at least one sensor (18; 31; 54) comprises a second sensor (31), optionally the second sensor (31) being a conductivity sensor.

[0067] In a 41staspect according to the previous aspect, the apparatus further comprises a temperature sensor (T4) associated to the second sensor (31) to measure a temperature of a fluid sensed by the second sensor (31) and allow for temperature compensation of the property of the fluid flowing through the second sensor (31).

[0068] In a 42ndaspect according to any one of the previous two aspects, when depending on aspect 35, wherein the second sensor (31) is located on the evacuation line (40), optionally a closure valve (V12) of the plurality of valves being located on the evacuation line (40) downstream of the second sensor (31) to selectively close a fluid communication to the drain (27).

[0069] In a 43rdaspect according to any one of the previous aspects, the plurality of valves comprises a water inlet valve (V3) placed on the main fluid line (3) upstream the first junction point (]1) and the second junction point (]2).

[0070] In a 44thaspect according to any one of the previous aspects, the apparatus further comprises a pressure regulator (41) placed on the main fluid line (3) upstream the first junction point (j1) and the second junction point (]2), optionally downstream a water inlet valve (V3) .

[0071] In a 45thaspect according to any one of the previous aspects, the fluid circuit (2) comprises a first service line (43) fluidly connecting the main fluid line (3) to the first dosing line (10), particularly at the first concentrate access (7).

[0072] The first service line (43) may be used for heat disinfection of the first dosing line (10) and the first concentrate access (7), when the concentrate is not connected typically at concentrate replacement.

[0073] In a 46thaspect according to the previous aspect, the plurality of valves comprises a first service valve (V1 ) to selectively prevent or allow fluid flow in the first service line (43), optionally the first service valve (V1) being located on the main fluid line (3) and configured to always allow a fluid flow along the main fluid line (3) and to selectively allow a simultaneous fluid flow through the first service line (43).

[0074] Notably the first service valve (V1 ) is located upstream of the water inlet valve (V3) .

[0075] In a 47thaspect according to any one of the previous aspects, the fluid circuit (2) comprises a second service line (44) fluidly connecting the main fluid line (3) to the second dosing line (15), particularly at the second concentrate access (12).

[0076] The second service line (44) may be used for heat disinfection of the second dosing line (15) and second concentrate access (12), when the concentrate is not connected typically at concentrate replacement.

[0077] In a 48thaspect according to the previous aspect, the plurality of valves comprises a second service valve (V2) to selectively prevent or allow fluid flow in the second service line (44), optionally the second service valve (V2) being located on the main fluid line (3) and configured to always allow a fluidflow along the main fluid line (3) and to selectively allow a simultaneous fluid flow through the second service line (43).

[0078] Notably the second service valve (V2) is located upstream of the water inlet valve (V3).

[0079] In a 49thaspect according to any one of the previous aspects, the apparatus further comprises a first pressure sensor (P1) located on the main fluid line (3) between the first injection point (j1) and the second injection point (j2).

[0080] In a 50thaspect according to any one of the previous aspects, the apparatus further comprises a secondary mixing chamber (20) placed on the main fluid line (3) and located downstream of the first injection point (j1) and the second injection point (]2) and upstream of the mixing chamber (17).

[0081] The purpose of the secondary mixing chamber (20) is to equalize the (large) concentration differences downstream of the first and second injection points (j1 , j2). It allows an improved mixing and a stable (e.g., conductivity) measurement.

[0082] In a 51staspect according to any one of the previous aspects, the apparatus further comprises a heater (21) configured to heat the fluid flowing in the main fluid line (3), the heater being placed downstream at least one of the first injection point (j1) and the second injection point (j2), in particular the heater (21 ) being placed upstream of the mixing chamber (17) and optionally upstream of the main pump (6).

[0083] In a 53rdaspect according to the previous aspect, the apparatus further comprises an outlet temperature sensor (T2) configured to sense a temperature of the fluid flowing in the main fluid line (3) downstream the heater (21), in particular the control unit (19) configured to control the heater (21) based on a temperature measured by said outlet temperature sensor (T2).

[0084] In a 54thaspect according to any one of the previous two aspects, the apparatus further comprises an inlet temperature sensor (T1) configured to sense a temperature of the fluid flowing in the main fluid line (3) upstream the heater (21).

[0085] The inlet temperature sensor (T1) may sense the temperature in the coldest point in the fluid circuit (2) during heat disinfection and optionally provide a feedback to the control unit (19) to control the heater (21).

[0086] In a 55thaspect according to any one of the previous three aspects, the heater (21) is configured to control a temperature of the fluid flowing in the main fluid line (3) to a temperature of at least 30°C and more specifically at least 37°C.

[0087] Notably, the temperature control to a set temperature (e.g., 37° - usually higher than the ambient temperature) may improve the conductivity measurements if the conductivity cell is calibrated to give the correct conductivity at approximately this temperature; of course, the conductivity cell may be equipped with temperature compensation making it possible to allow the conductivity cell to operate at other temperatures.

[0088] In a 56thaspect according to any one of the previous aspects, the apparatus further comprises a presence-of-flow sensor (42) for detecting presence of a fluid flow in the main line.

[0089] In a 57thaspect according to the previous aspect, the presence-of-flow sensor (42) is a pressure sensor (P3) configured to detect a pulsation flow in the main fluid line (3), in particular the pressure sensor (P3) being located on the main fluid line (3) immediately upstream or downstream of the main pump (6) (i.e., in close proximity).

[0090] In a 58thaspect according to any one of the previous two aspects, when depending from any one of aspects 51 to 55, wherein the control unit (19) is configured to activate the heater (21 ) upon the presence-of-flow sensor (42) detects the presence of a fluid flow in the main line (3).

[0091] In a 59thaspect according to any one of the previous aspects, the apparatus further comprises a filter (24) placed downstream the mixing chamber (17) and downstream the at least one sensor (18), in particular said filter (24) being an ultrafilter.

[0092] The filter (24) aims at reducing any microbial contamination before fluid delivery to a receiving device or means (23), such as e.g., an external dialysis unit or a set of bags.

[0093] In a 60thaspect according to the previous aspect, the filter (24) comprises: a semipermeable membrane separating a filter volume into an inlet chamber and an outlet chamber; an inlet (24a) connected to the main fluid line (3) for receiving fluid from the main fluid line (3); an outlet (24b) connected to the main fluid line (3) for feeding filtered fluid to the main fluid line (3), the outlet (24b) being part of the outlet chamber; and an auxiliary outlet (24c), the inlet (24a) and the auxiliary outlet (24c) being part of the inlet chamber.

[0094] In a 61staspect according to the previous aspect, the fluid circuit (2) further comprises a filter flushing line (25) connected to the auxiliary outlet (24c) and in fluid communication with a drain (27), particularly through an evacuation line (40), the plurality of valves including a closure valve (V10) located on the filter flushing line (25) and the control unit (19) being configured to control the closure valve (V10) to selectively opening and closing the filter flushing line (25).

[0095] The filter (24) is flushed to drain (27) using the valve (V10) and the filter flushing line (25). A second conductivity sensor (31) located in evacuation line (40) downstream of the filter (24) may sense the conductivity of the fluid before it is delivered to the dialysis unit (23). In case the filter (24) is filled with fluid having a composition that differs from a target composition (e.g., water or wrong first and / or second concentrate concentration), the fluid needs to be flushed out to drain (27) until the conductivity is sufficiently close to the target and / or to the conductivity of the first conductivity sensor (18).

[0096] In a 61stbis aspect according to any one of the previous two aspects, the outlet (24b) of the filter (24) is fluidly connectable either to a drain (27) via an evacuation line (40), or to the outlet point (5), the at least one sensor (18; 31 ; 54) being located on the evacuation line (40), one or more valves (V7, V8, V9, V12, V14) of the plurality of valves being located between the outlet (24b), the drain (27) and the outlet point (5),wherein the control unit (19) is configured to control said one or more valves (V7, V8, V9, V12, V14) to selectively allow fluid flow from the outlet (24b) towards the drain or towards the outlet point, the control unit (19) being further configured to execute a control procedure to check the property of the mixture of water, first concentrate, and second concentrate exiting the filter (24), the control procedure including:• controlling said one or more valves (V7, V8, V9, V12, V14) to allow fluid flow from the outlet (24b) to the drain (27) via the evacuation line (40), in particular preventing the fluid flow towards the outlet point (5);• checking the property of the fluid by the at least one sensor;• if the property of the fluid satisfy a safety check criteria, controlling said one or more valves (V7, V8, V9, V12, V14) to allow fluid flow from the outlet (24b) to the outlet point (5), in particular preventing the fluid flow towards the drain (27).

[0097] The control unit (19) verifies that the property, e.g., conductivity, of the fluid lies within a safe range around the medical fluid property set value (safety check criteria). If this is the case, the medical fluid may be used and therefore may be directed to the external device. In case the property e.g., conductivity, lies outside safety values, the medical fluid is discarded through the drain (27).

[0098] In a 62ndaspect according to any one of the previous four aspects, the fluid circuit (2) further comprises an air intake line (45) to allow air to enter the main fluid line (3) and the plurality of valves includes an air intake valve (V4) located on the air intake line (45) and the control unit (19) being configured to control the air intake valve (V4) to selectively opening and closing the air intake line (45).

[0099] In a 63rdaspect according to the previous aspect, the apparatus further comprises an air filter (46) located on the air intake line (45) to filter air entering the main fluid line (3).

[0100] The air filter (46) is a bacteria retaining filter to keep the intake air sterile when performing e.g., an integrity test of the filter / s (24; 26).

[0101] In a 64thaspect according to any one of the previous six aspects, further comprising a second filter (26) in series with the filter (24) on the main fluid line (3), said second filter (26) being placed downstream the mixing chamber (17) and downstream the at least one sensor (18), in particular said second filter (26) being an ultrafilter.

[0102] The second filter (26) aims at further reducing any microbial contamination before fluid delivery to the external dialysis unit (23).

[0103] In a 65thaspect according to the previous aspect, the second filter (26) comprises: a semipermeable membrane separating the filter into an inlet chamber and an outlet chamber; an inlet (26a) connected to the main fluid line (3) for receiving fluid from the main fluid line (3); an outlet (26b) connected to the main fluid line (3) for feeding filtered fluid to the main fluid line (3), the outlet (26b) being part of the outlet chamber; and an auxiliary outlet (26c), the inlet (26a) and the auxiliary outlet (26c) being part of the inlet chamber.

[0104] In a 66thaspect according to the previous aspect, the fluid circuit (2) further comprises a second flushing line (28) connected to the auxiliary outlet (26c) of the second filter (26) and in fluid communication with a drain (27), particularly through an evacuation line (40), a valve (V11) being active on the second flushing line (28) and the control unit (19) being configured to control the valve (V11) to selectively opening and closing the second flushing line (28).

[0105] The second filter (26) is flushed to drain (27) using the valve (V11) and the second flushing line (28).

[0106] In a 66thbis aspect according to any one of the previous two aspects, the outlet (26b) of the second filter (26) is fluidly connectable either to a drain (27) via an evacuation line (40), or to the outlet point (5), the at least one sensor (31 ) being located on the evacuation line (40), one or more valves (V7, V8, V12, V14) of the plurality of valves being located between the outlet (26b), the drain (27) and the outlet point (5), wherein the control unit (19) is configured to control said one or more valves (V7, V8, V12, V14) to selectively allow fluid flow from the outlet (26b) towards the drain or towards the outlet point, the control unit (19) being further configured to execute a control procedure to check the property of the mixture of water, first concentrate, and second concentrate exiting the second filter (26), the control procedure including:• controlling said one or more valves (V7, V8, V12, V14) to allow fluid flow from the outlet (26b) to the drain (27) via the evacuation line (40), in particular preventing the fluid flow towards the outlet point (5);• checking the property of the fluid by the at least one sensor;• if the property of the fluid satisfy a safety check criteria, controlling said one or more valves (V7, V8, V12, V14) to allow fluid flow from the outlet (26b) to the outlet point (5), in particular preventing the fluid flow towards the drain (27).

[0107] The control unit (19) verifies that the property, e.g., conductivity, of the fluid lies within a safe range around the medical fluid property set value (safety check criteria). If this is the case, the medical fluid may be used and therefore may be directed to the external device. In case the property e.g., conductivity, lies outside safety values, the medical fluid is discarded through the drain (27).

[0108] A second conductivity sensor (31) located in evacuation line (40) downstream of the second filter (26) may sense the conductivity of the fluid before it is delivered to the dialysis unit (23). In case the second filter (26) is filled with fluid having a composition that differs from a target composition (e.g., water or wrong first and / or second concentrate concentration), the fluid needs to be flushed out to drain (27) until the conductivity is sufficiently close to the target and / or to the conductivity of the first conductivity sensor (18).

[0109] In a 67thaspect according to the previous aspect, the filter flushing line (25) and the second flushing line (28) share a common line tract (25a) in fluid communication with the drain (27), particularly through an evacuation line (40), optionally the plurality of valves includes a shut valve (V14)located on the common line tract (25a) and the control unit (19) being configured to control the shut valve (V14) to selectively opening and closing the common line tract (25a).

[0110] The common line tract (25a) is directly connected to the evacuation line (40).

[0111] In a 68thaspect according to any one of the previous four aspects, the main fluid line (3) comprises a delivery tract (30) interposed between the second filter (26) and the outlet point (5).

[0112] In a 69thaspect according to the previous aspect, the apparatus further comprises a delivery line pressure sensor (P2) located to measure a pressure in the delivery tract (30).

[0113] In a 70thaspect according to any one of the previous two aspects, the plurality of valves comprises a delivery valve (V8) located on the delivery tract (30) and interposed between the outlet (26b) of the second filter (26) and the outlet point (5) and configured to selectively prevent or allow a fluid flow.

[0114] In a 71staspect according to the previous aspect, the fluid circuit (2) comprises a bypass conduit (33) fluidly connecting the delivery tract (30) to a drain (27), particularly through an evacuation line (40), a closure valve (V7) being placed on the bypass conduit (33) to selectively prevent or allow a fluid flow therein.

[0115] The bypass conduit (33) is directly connected to common line tract (25a) in turn directly connected to the evacuation line (40).

[0116] In a 72ndaspect according to the previous aspect, the delivery valve (V8) is located on the main fluid line (3) and configured to allow a fluid flow from the main fluid line (3) to the bypass conduit (33) and to selectively allow a fluid flow from a main fluid line tract upstream of the delivery valve (V8) to a main fluid line tract downstream of the delivery valve (V8) towards the outlet point (5).

[0117] Notably the delivery valve (V8) is located upstream of the closure valve (V7).

[0118] In a 73rdaspect according to any one of the previous nine aspects, the main fluid line(3) comprises a connecting tract (29) interposed between the filter (24) and the second filter (26) and connecting the outlet (24b) of the filter (24) to the inlet (26a) of the second filter (26), in particular a valve (V9) being interposed between the outlet (24b) of the filter (24) and the inlet (26a) of the second filter (26) and configured to selectively prevent or allow a fluid flow.

[0119] In a 74thaspect according to any one of the previous aspects, the apparatus further comprises: o a first concentrate container (9) containing a first concentrate (F), with a port (8) fluidly connected to the first concentrate access (7), in particular the first concentrate (F) being in liquid form; and / or o a second concentrate container (14) containing a second concentrate (S), with a port (13) fluidly connected to the second concentrate access (12), in particular the second concentrate (S) being in liquid form.

[0120] If in liquid form, the nominal dilution factor of the first concentrate (F) may be between 15x and 30x, e.g., about 25x.

[0121] If in liquid form, the second concentrate (S) may be a liquid concentrate between 50% and 80% weight / volume, e.g., about 65% weight / volume.

[0122] In a 75thaspect according to any one of the previous aspects, the first concentrate (F) comprises electrolytes and / or a buffer, in particular said first concentrate being intended for peritoneal dialysis or to haemo-dialysis.

[0123] In a 76thaspect according to any one of the previous aspects, the first concentrate (F) comprises at least one substance in the group comprising sodium chloride (NaCI), sodium lactate (NaLa), calcium chloride (CaCfe), and magnesium chloride (MgCh).

[0124] In particular, the first concentrate (F) includes all the above substances.

[0125] In a 77thaspect according to any one of the previous aspects, the first concentrate (F) is a liquid concentrate or a dry concentrate.

[0126] In a 78thaspect according to any one of the previous aspects, the second concentrate (S) comprises an osmotic agent, such as glucose.

[0127] In a 78thbis aspect according to any one of the previous aspects 1 to 77, the second concentrate (S) comprises bicarbonate.

[0128] In a 79thaspect according to any one of the previous aspects, the second concentrate (S) is a liquid concentrate or a dry concentrate.

[0129] In an 80thaspect according to any one of the previous aspects, the control unit (19) is configured to receive an input request from a dialysis unit (23), for example a peritoneal dialysis (PD) cycler, based on the input request, the control unit (19) being configured to start a dialysis fluid generation by commanding activation of the main pump (6), the first dosing pump (11), and the second dosing pump (16), in particular the control unit (19) is configured to set a main pump flow rate based on the received input request.

[0130] In an 81staspect according to any one of the previous aspects, the mixing chamber (17) comprises an inlet (17a) fluidly connected to the main fluid line (3) upstream of the mixing chamber (17) and an outlet (17b) fluidly connected to the main fluid line (3) downstream of the mixing chamber (17), the fluid circuit (2) comprising a mixing chamber discharge conduit (32) further connecting a top of the mixing chamber (17) to the main fluid line (3) which is further connected to drain (27), or connected to drain (27) without being connected to the main fluid line (3), the plurality of valves including either a discharge valve (V6) interposed between the mixing chamber (17) and the main fluid line (3) or a discharge valve (V6’) interposed between the mixing chamber (17) and the drain (27), the discharge valve (V6; V6’) being configured to selectively prevent or allow a fluid flow in the mixing chamber discharge conduit (32).

[0131] In an 82ndaspect according to any one of the previous aspects, the mixing chamber discharge conduit (32) may allow for (intermittent) release of gas captured in the mixing chamber (17) and / or may be used as part of sequences where the mixing chamber (17) is bound to receive gas, such as e.g. during priming of the fluid circuit (2).

[0132] In an 83rdaspect according to any one of the previous aspects, the fluid circuit (2) comprises a recirculation conduit (34) fluidly connecting a point of the main fluid line (3) close to the outlet point (5) to a point of the main fluid line (3) upstream the first injection point (j1) and the second injection point (j2), the plurality of valve including a closure valve (V5) placed on the recirculation conduit (34) and configured to selectively prevent or allow a fluid flow therein, in particular, the recirculation conduit (34) being further connected to drain (27) via a common line tract (25a) and / or an evacuation line (40).

[0133] The recirculation conduit (34) and closure valve (V5) may enable a recirculation path from the auxiliary outlet / s (24c; 26c) of the filter / s (24; 26) and the main fluid line (3) downstream of the filter / s (24; 26) to upstream the main pump (6) and may be used during heat disinfection.

[0134] In an 84thaspect according to any one of the previous aspects, the fluid circuit (2) comprises a return conduit (38) connecting a secondary port (61) receiving e.g., an effluentfrom the patient, to the drain (27).

[0135] In an 85thaspect according to any one of the previous aspects, the fluid circuit (2) comprises a water recirculation conduit (36) connecting a point of the main fluid line (3) upstream of the first injection point (j1) and the second injection point (]2) with an external point, the plurality of valves comprising a recirculation valve (V15) configured to selectively prevent or allow a fluid flow in the water recirculation conduit (36).

[0136] In an 86thaspect according to any one of the previous aspects, the apparatus further includes a supporting structure (37) housing: o the fluid circuit (2), o the first dosing pump (11), o the second dosing pump (16), o the main pump (6), and the plurality of valves (V1 to Vn).

[0137] In an 87thaspect according to any one of the previous aspects, the apparatus is for the online preparation of peritoneal dialysis (PD) fluid from water and concentrates, in particular upon request from a PD cycler.

[0138] In an 87thbis aspect according to any one of the previous aspects, the apparatus is configured to prepare the medical fluid and simultaneously deliver the medical fluid to the outlet point (5), e.g., in order to be used immediately and / or in real time by the external device or to be stored in an external container.

[0139] In other words, the apparatus does not include a container for storing a batch preparation of the medical fluid for use after the preparation steps have been completed. The medical fluid is prepared on demand for an instantaneous use and is dispensed directly from the apparatus without being stored in the apparatus intermittently.

[0140] Of course, in a different design of the apparatus / fluid circuit a reservoir may be included in the fluid circuit, if this is appropriate or necessary for other purposes.

[0141] In an 88thaspect, optionally according to any one of the previous aspects, a medical fluid generation apparatus (1) is provided and comprises: a fluid circuit (2) including a main fluid line (3) developing between an inlet point (4) for receiving water and an outlet point (5) connectable to a treatment medical device, a main pump (6) located on the main fluid line (3) to pump fluid at least in the main fluid line (3), wherein the fluid circuit (2) further includes: o a first concentrate access (7) fluidly connectable to a port (8) of a first concentrate container (9) containing a first concentrate (F), o a first dosing line (10) putting in fluid communication the first concentrate access (7) and the main fluid line (3) at a first injection point (j 1) located between the inlet point (4) and the outlet point (5), o a first concentrate auxiliary access (50) fluidly connectable to an auxiliary port (51) of the first concentrate container (9), o an auxiliary line (58) for the first concentrate container (9) putting in fluid communication the first concentrate auxiliary access (50) and the main fluid line (3) at an injection point located between the inlet point (4) and the outlet point (5), for example at the first injection point (j1), o a second concentrate access (12) fluidly connectable to a port (13) of a second concentrate container (14) containing a second concentrate (S), o a second dosing line (15) putting in fluid communication the second concentrate access (12) and the main fluid line (3) at a second injection point (]2) located between the inlet point (4) and the outlet point (5); o a second concentrate auxiliary access (52) fluidly connectable to an auxiliary port (53) of the second concentrate container (14), o an auxiliary line (59) for the second concentrate container (14) putting in fluid communication the second concentrate auxiliary access (52) and the main fluid line (3) at an injection point located between the inlet point (4) and the outlet point (5), for example at the second injection point (j2), a first dosing pump (11) configured to pump fluid in the first dosing line (10), a second dosing pump (16) configured to pump fluid in the second dosing line (15), a plurality of valves (V1 , .... Vn) located on the fluid circuit (2) and configurable to define different fluid paths for the fluid inside the fluid circuit (2), a control unit (19) configured to operate the plurality of valves to define the different fluid paths inside the fluid circuit (2),wherein the control unit (19) is configured to execute a dry concentrate dissolution procedure comprising one or more of a first concentrate dissolution sequence and a second concentrate dissolution sequence, wherein, during execution of the first concentrate dissolution sequence, the control unit (19) is configured to:• operate the main pump (6) and / or the first dosing pump (11) to pump water through at least one tract of either the first dosing line (10) or the auxiliary line (58) of the first concentrate container (9) towards the first concentrate container (9); and wherein, during execution of the second concentrate dissolution sequence, the control unit (19) is configured to:• operate the main pump (6) and / or the second dosing pump (16) to pump water through at least one tract of either the second dosing line (15) or the auxiliary line (59) of the second concentrate container (14) towards the second concentrate container (14).

[0142] In an 89th aspect according to the previous aspect, wherein the fluid circuit (2) further comprises a return line (60) connected to the main fluid line (3) at a third junction point (j3), optionally positioned downstream of at least one sensor (18; 31; 54), the return line (60) being fluidly connected to either the first dosing line (10) at a dosing line intermediate point (10a) or to the auxiliary line (58) of the first concentrate container (9) at an intermediate point, wherein, during execution of the first concentrate dissolution sequence, the control unit (19) is configured to operate the main pump (6) to pump water through the return line (60).

[0143] In a 90thaspect according to any one of the previous two aspects, wherein the return line (60) includes a branch line (60a) branching off from the return line (60) at a branch point (60b), the branch line (60a) being fluidly connected either to the second dosing line (15) at a dosing line intermediate point (15a) or to the auxiliary line (59) of the second concentrate container (9) at an intermediate point, wherein, during execution of the second concentrate dissolution sequence, the control unit (19) is configured to operate the main pump (6) to pump water through the branch line (60a).

[0144] In a 91staspect according to any one of the previous three aspects, wherein, during execution of the first concentrate dissolution sequence, the control unit (19) is configured to operate the main pump (6) to pump water through the first dosing line (10).

[0145] In a 92ndaspect according to any one of the previous four aspects, wherein, during execution of the second concentrate dissolution sequence, the control unit (19) is configured to operate the main pump (6) to pump water through the second dosing line (15).

[0146] In a 93rdaspect according to any one of the previous five aspects, wherein the first dosing line (10) and the auxiliary line (58) of the first concentrate container (9) form part of a first dissolution loop, wherein, during execution of the first concentrate dissolution sequence, the control unit (19) is configured to control the first dosing pump (11 ) to recirculate the water and dissolved concentrate along the first dissolution loop.

[0147] In a 94thaspect according to the previous aspect, wherein, during execution of the first concentrate dissolution sequence, the control unit (19) is configured to control the first dosing pump (11) backwards to recirculate the water and dissolved concentrate, the water and dissolved concentrate flowing from the first dosing pump (11) towards the first concentrate access (7).In particular, the connection of the auxiliary line (58) to the first concentrate container (9) is below the liquid level in the first concentrate container (9). If not, reversing the pumping direction may cause the risk of pumping air in the fluid circuit because air is present in the powder of the dry concentrate inside the container.

[0148] In a 95thaspect according to any one of the previous seven aspects, wherein the second dosing line (15) and the auxiliary line (59) of the second concentrate container (14) form part of a second dissolution loop, wherein, during execution of the second concentrate dissolution sequence, the control unit (19) is configured to control the second dosing pump (16) to recirculate the water and dissolved concentrate along the second dissolution loop, optionally the recirculation in the second dissolution loop being executed simultaneously with the recirculation in the first dissolution loop.

[0149] In a 96thaspect according to the previous aspect, wherein, during execution of the second concentrate dissolution sequence, the control unit (19) is configured to control the second dosing pump (16) backwards to recirculate the water and dissolved concentrate, the water and dissolved concentrate flowing from the second dosing pump (16) towards the second concentrate access (12).As previously noted, the connection of the auxiliary line (59) to the second concentrate container (14) is below the liquid level in the second concentrate container (14). If not, reversing the pumping direction may cause the risk of pumping air in the fluid circuit because air is present in the powder of the dry concentrate inside the container.

[0150] In a 97thaspect according to the previous aspect 89, wherein the return line (60), a portion of the first dosing line (10) interposed between the intermediate point (10a) and the first concentrate access (7), the auxiliary line (58) of the first concentrate container (9) and a portion of the main fluid line (3) between the first injection point (]1) and the third injection point (]3) form part of a third dissolution loop, wherein, during execution of the first concentrate dissolution sequence, the control unit (19) is configured to control the main pump (6) to recirculate the water and dissolved concentrate along the third dissolution loop.

[0151] In a 98thaspect according to the previous aspect 90, wherein a portion of the return line (60) interposed between the third injection point (]3) and the branch point (60b), the branch line (60a), a portion of the second dosing line (15) interposed between the intermediate point (15a) and the second concentrate access (12), the auxiliary line (59) of the second concentrate container (14) and a portion of the main fluid line (3) between the second injection point (]2) and the third injection point (]3) form part of a fourth dissolution loop,wherein, during execution of the second concentrate dissolution sequence, the control unit (19) is configured to control the main pump (6) to recirculate the water and dissolved concentrate along the fourth dissolution loop.

[0152] Additionally, any of the above aspects, or portions thereof, and / or any of the features, functionality, and alternatives described in connection with any one or more of Figs. 1 to 6 may be combined with any of the features, functionality and alternatives described in connection with any other of Figs. 1 to 6.

[0153] It is accordingly an advantage of the present disclosure to provide an apparatus that, upon request, makes online fresh dialysis fluid that may be directly delivered to an e.g., PD cycler.

[0154] It is another advantage of the present disclosure to provide an apparatus that makes fresh dialysis fluid for a patient, for example for home dialysis, only requiring the use of liquid concentrates and / or dry concentrates thereby reducing the medical fluid bag handling.

[0155] It is a further advantage of the present disclosure to provide an apparatus that makes fresh dialysis fluid with a simple hydraulic circuit requiring only a single pump working on a main fluid line and capable of managing the various medical fluid production steps.

[0156] It is yet a further advantage of the present disclosure to provide an apparatus that makes fresh dialysis fluid which may be eventually placed in bags or containers for later use.

[0157] Moreover, it is an advantage to make fluids, such as PD fluids, CRRT fluids, lactated ringers and the like closer in time and distance to a point of use for the patient, which lessens the amount of supplies that have to be stored, e.g., at a patient’s home.

[0158] It is still a further advantage to prepare PD fluid using one or more concentrates.

[0159] Another advantage of the present disclosure is to provide a durable fluid circuit that is therefore reusable and reduces the efforts on the patient when preparing the medical fluid as e.g., there is no need to set up disposable lines and / or dress the medical apparatus with fluid flow paths. Further, less material waste is generated.

[0160] Additional features and advantages are described in, and will be apparent from, the following Detailed Description and the Figures. The features and advantages described herein are not all- inclusive and, in particular, many additional features and advantages will be apparent to one of ordinary skill in the art in view of the figures and description. Also, any particular embodiment does not have to have all of the advantages listed herein and it is expressly contemplated to claim individual advantageous embodiments separately. Moreover, it should be noted that the language used in the specification has been selected principally for readability and instructional purposes, and not to limit the scope of the inventive subject matter.BRIEF DESCRIPTION OF THE FIGURES

[0161] Figure 1 is a schematic view of a fluid circuit of a medical fluid generation apparatus according to a first embodiment of the present invention;

[0162] Figure 2 is a schematic view of a fluid circuit of a medical fluid generation apparatus according to a second embodiment of the present invention;

[0163] Figure 3 is a schematic view of a fluid circuit of a medical fluid generation apparatus according to a third embodiment of the present invention;

[0164] Figure 4 is a flow chart showing a schematic timeline of mixing operations during a concentrate in-use period;

[0165] Figure 5 is a schematic view of the actual first concentrate mixing sequence to determine the electrolyte pump speed based on conductivity readings;

[0166] Figure 6 is a schematic view of the second concentrate mixing sequence, wherein electrolyte and glucose control steps are performed to find the pump speed ratios that yields the correct fluid composition;

[0167] Figure 7 is a flow chart representing steps performed by the medical fluid generation apparatus to execute the medical fluid preparation procedure.DETAILED DESCRIPTIONMEDICAL FLUID GENERATION APPARATUS

[0168] Considering the embodiment shown in figure 1, a medical fluid generation apparatus 1 for preparing a medical fluid such as dialysis fluid, and in particular PD fluid or HD fluid, including fluid for CCRT, is schematically outlined.

[0169] Various embodiments of the fluid circuit are described with particular reference to figures 1 to 3, all of which fall within the scope of the present invention. Where the same reference number is used, the same component is referred to in the different embodiments and the description of such a component given with respect to one embodiment applies equally to the others.

[0170] The medical fluid apparatus 1 comprises a supporting structure 37 (only schematically represented) defining a housing for containing different inner parts and / or inner elements and / or inner components of the medical fluid apparatus 1. Moreover, the supporting structure 37 provides various external connection areas which allow one or more external elements and / or external components of the medical fluid apparatus 1 to be operatively connected to the aforementioned internal parts and / or internal elements and / or internal components of the medical fluid apparatus 1 and to interact with them in order to perform various processes and functions which will be described throughout of the description.

[0171] The supporting structure 37 houses a fluid circuit 2 which includes a main fluid line 3 provided with an inlet point 4 for receiving water. The supporting structure 37 encloses the fluid circuit 2, the valves connected to the fluid circuit, pumps and other internal components (as further described below) thereby protecting them from direct access by the user. In addition, the fluid circuit 2 is durable (i.e., non-disposable) and is used each time it is necessary to produce medical fluid, in the case after proper disinfection. Of course, in a different and alternative embodiment, the fluid circuit may be a disposable circuit.

[0172] The supporting structure 37 has an entrance 39 for connection to a water source. Depending on the specific embodiment of the medical fluid generation apparatus 1 , either already pure water is supplied to the apparatus through the entrance 39 or water that needs to be purified is provided. Indeed, the medical fluid generation apparatus 1 may or may not be provided with a water purification device 22.

[0173] Regardless the configuration, the inlet point 4 of the main fluid line 3 receives pure water, e.g., water that has been treated to remove impurities, contaminants, chemicals, and dangerous microorganisms, as well as solutes. Pure water may be obtained by distillation, deionization, reverse osmosis, or other suitable process and that meets the definition of pure water in the relevant Pharmacopeia. For example, pure water may be produced with a known reverse osmosis device. In one example (see Figure 1), a purification device 22 (e.g., the aforementioned reverse osmosis device) may be included within the supporting structure 37, upstream of the inlet point 4. Water, such as tap water, enters the supporting structure through the entrance 39 for water and reaches the purification device 22. Water is purified and sent to the inlet point 4.

[0174] In an alternative embodiment (see for example figure 2), the pure water arrives directly at entrance 39, in particular from an external supply source that may be chosen among different known supply sources. Preferably, the external supply source may comprise a water purification device 22 configured to provide pure water to the entrance 39 and consequently to the inlet point 4 for receiving pure water. The water purification equipment includes a central water purification station configured to feed the entrance 39 and the inlet point 4 or a standalone water purifier configured to feed the entrance 39 and the inlet point 4. In order to allow the external supply source to feed the inlet point 4 with the pure water, the supporting structure 37 is externally provided with the proper entrance connection. In an embodiment, entrance 39 and inlet point 4 may be coincident. Notably, also embodiments of figures 2 and 3 may include a purification device 22 downstream the entrance 39 as an alternative design. The purification device 22 upstream the entrance 39 in figure 2 may then not be needed.

[0175] In all the embodiments, the supporting structure 37 also houses a main pump 6, preferably a volumetric pump 6, configured to operate on the main fluid line 3 to circulate at least one fluid / solution, at least in the main fluid line 3 of the fluid circuit 2. If the main pump is not a volumetric pump other sensors, such as a flow meter, may be added to ensure the desired flow rate. As apparent in the following description, one single pump 6 operating in the main fluid line 3 may be sufficient for the working of the apparatus. More in detail, such pump 6 may always move the fluid in the same direction (i.e., is never operated in reverse or backwards, hence, it is unidirectional). In an alternative embodiment, the pump may be bi-directional (i.e., the flow may be reversed).

[0176] The supporting structure 37 of the various embodiments houses a respective plurality of valves V1 to Vn configured to operate on the fluid circuit 2 to set different fluid paths for the fluid withinthe fluid circuit 2, in particular according to different processes and operations to be executed by the medical fluid generation apparatus 1. In general a valve has an open condition 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.

[0177] The medical fluid generation apparatus 1 also comprises a control unit 19 configured to control the apparatus itself including to operate at least the pump 6 and the plurality of valves in order to control and manage the configuration of the plurality of valves and establish the fluid paths to be followed by the fluid or the fluids within the fluid circuit 2. Advantageously, the control unit 19 is electrically and / or electronically connected to the plurality of valves and the other parts and / or elements and / or components of the medical fluid generation apparatus 1 , by a plurality of known electrical and / or electronic connections not shown in the accompanying figures. Alternatively, the control unit 19 may be connected to the plurality of valves and the other parts and / or elements and / or components of the medical fluid generation apparatus 1, through a wireless connection system requiring at least one operatively interposed unit capable of transmitting and receiving one or more signals by using various communication protocols known in the art. The control unit 19 comprises all necessary components, hardware, and software, to interact with, monitor and control all necessary aspects of the apparatus 1 and its use. The control unit 19 comprises at least a processor and memory. The processor may comprise digital and analog circuity structured as a processor, application specific integrated circuit (“ASIC”), controller, etc. and may include one or more processing units. The memory may include one or more memory units.

[0178] As shown in Figure 1 , the supporting structure 37 is provided with two connectors / accesses suitable for connection to a respective container, namely a first concentrate access 7 and a second concentrate access 12, in fluid communication with the fluid circuit 2 inside the supporting structure 37 to allow deliver of concentrates from a connected component to the internal fluid circuit.

[0179] In particular, the first primary concentrate access 7 is designed for fluid connection to a first concentrate container 9 and is in fluid communication with the main fluid line 3 of the fluid circuit 2. The first concentrate container 9 may have only one outlet, for example because it contains a liquid concentrate.

[0180] The second concentrate access 12 is designed for fluid connection to a second concentrate container 14 and is in fluid communication with the main fluid line 3 of the fluid circuit 2. The second concentrate container 14 may have only one outlet, for example because it contains a liquid concentrate.

[0181] As mentioned, the medical fluid generation apparatus 1 is provided with at least one concentrate container and preferably two concentrate containers 9, 14 having each at least one port 8, 13 that may be or is put in fluid communication with the main fluid line 3 of the fluid circuit 2 via the corresponding container access 7, 12.

[0182] The medical fluid generation apparatus 1 of the embodiment of figure 1 comprises a first concentrate container 9 having at least one port 8 that may be or is put in fluid communication with the mainfluid line 3 of the fluid circuit 2 and a second concentrate container 14 having at least one port 13 that may be or is put in fluid communication with the main fluid line 3 of the fluid circuit 2. Each of the first concentrate container 9 and the second concentrate container 14 defines, at least partially, a corresponding external additional part or extension of the fluid circuit 2 which may be connected to the corresponding first concentrate access 7 and the corresponding second concentrate access 12.

[0183] Considering the embodiments shown in figures 1 and 2 the first concentrate container 9 has only one port 8 in fluid communication with the main fluid line 3 of the fluid circuit 2 through the corresponding first concentrate access 7. Generally, when the first concentrate container 9 has only the first port 8 for connection to the first concentrate access 7, it contains a first liquid concentrate ready to be mixed with at least one other liquid (such as water) or another liquid concentrate still ready to be mixed or obtained by a corresponding dissolution procedure.

[0184] Differently, looking at the embodiment shown in figure 3, the first concentrate container 9 instead has two ports 8, 51 in fluid communication with the main fluid line 3 of the fluid circuit 2 at two different locations, as will be explained later in the description. Of course also the first concentrate container of the first and second embodiments of figures 1 and 2 may also alternatively have two respective ports, particularly when the first concentrate container 9 contains a dry concentrate to be dissolved prior to use.

[0185] Considering the embodiments shown in figures 1 and 2, the second concentrate container 14 has only one port 13 in fluid communication with the main fluid line 3 through the second concentrate access 12 of the fluid circuit 2. Generally, when the second concentrate container 14 has only the first port 13 for connection to the first concentrate access 12, it contains a second liquid concentrate ready to be mixed with at least one other liquid (such as water) or another liquid concentrate still ready to be mixed or obtained by a corresponding dissolution procedure. With reference to the simplified embodiment shown in figure 3, the second concentrate container 14 instead has two ports 13, 53 in fluid communication with the main fluid line 3 of the fluid circuit 2 at two different locations, as will be explained later in the description. Of course also the second concentrate container 14 of the first and second embodiments of figures 1 and 2 may also alternatively have two respective ports, particularly when the second concentrate container 14 contains a dry concentrate to be dissolved prior to use.

[0186] Correspondingly, the supporting structure 37 may present two, three or four accesses 7, 12, 50, 52 or a different number in case only one, two, three or four accesses are required (or more in case more accesses are needed); for example one first concentrate 9 may include two ports 8, 51 that have to be connected to the supporting structure 37, thereby requiring two respective accesses e.g., 7, 50, and one second container 14 may include just one port 13 to be connected to e.g., access 12. In this case, access 52 of figure 3 may be absent.

[0187] Regardless the specific embodiment to which it refers, the ports 8, 13, 51, 53 of the respective concentrate containers 9, 14 may be or are put in fluid communication with the main fluid line 3 of the fluid circuit 2 via the corresponding container accesses 7, 12, 50, 52 provided on the supportingstructure 37. Therefore, the container accesses 7, 12, 50, 52 of the supporting structure 37 allow the medical generation apparatus 1 to provide different configurations of the concentrate containers 9, 14 to be used, which may house dry concentrates to be dissolved and / or diluted and / or liquid concentrates to be diluted. In particular, the embodiment shown in figure 3, both the first and the second concentrate containers 9, 14 house a dry concentrate to be dissolved and / or diluted, whereas in the embodiments shown in figures 1 and 2, both the first and the second concentrate containers 9, 14 house a liquid concentrate to be diluted and mixed with another liquid concentrate. Any configuration with both dry and liquid concentrates in the required number is encompassed by all the embodiments of the present description.

[0188] The fluid circuit of the first embodiment - Figure 1

[0189] Referring now to the embodiment of figure 1, water is fed to the apparatus 1 through entrance 39. In the specific embodiment, water is treated by the water purification equipment 22 to provide purified water along main fluid line 3 downstream the inlet point 4. Water passes through first and second service valves V1 and V2 and through water inlet valve V3. Water inlet valve V3 selectively blocks or allows water flow along the main fluid line 3. Valve V1 selectively permits fluid flow along a first service line 43 fluidly connecting the main fluid line 3 to a first dosing line 10, particularly at the first concentrate access 7. This first service line 43 may be used to flush the first concentrate access 7 and / or during disinfection of the fluid circuit 2, including disinfection of the access 7.

[0190] Correspondingly, valve V2 selectively permits fluid flow along a second service line 44 fluidly connecting the main fluid line 3 to a second dosing line 15, particularly at the second concentrate access 12. This second service line 44 may be used to flush the first concentrate access 12 and / or during disinfection of the fluid circuit 2, including disinfection of the access 12.

[0191] A pressure regulator 41 is located on the main fluid line 3 downstream of the water inlet valve V3 and upstream of injection points j1 and j2 where the concentrates are injected into the main fluid line 3. The pressure regulator 41 creates a preferred pressure level on the suction side of the main pump 6 and may prevent undesired pressure fluctuations during operation of the apparatus.

[0192] Looking at the fluid circuit of figure 1 , it can be seen that the main fluid line 3 downstream of the pressure regulator 41 is directed to flush one or more of (and in particular all) the main pump 6, a first dosing pump 11 and a second dosing pump 16. Indeed, one or more of, and possibly all, these pumps are volumetric pumps. Dependent on design, a volumetric liquid pump may require periodic flushing with water for several reasons. For example water can be used to remove any residue or solid particles that accumulate in the pumping system over time and which could compromise the pump's efficiency or cause blockages. If different types of liquids are being used with the same pump, flushing with water may be used to clear out residues of one liquid before switching to another. This can prevent cross-contamination between fluids and preserve the purity of the transferred liquids. Finally, regular flushing with water can help maintain the pump optimal performance by cooling the pump during operation and ensuring that internal mechanisms are free from obstructions or deposits that could affect flow and pressure.

[0193] More specifically, the first dosing line 10 puts the first concentrate access 7 into fluid communication with the main fluid line 3 at a first injection point j1 located between the inlet point 4 and an outlet point 5, where the medical fluid leaves the apparatus for use by, e.g., an external device, such as a dialysis unit 23. More specifically, the first injection point j1 is located downstream of the water inlet valve V3 and the pressure regulator 41. Furthermore, in the embodiment of Figure 1, the first injection point j1 is also located downstream of the flushing channels described above through which the pumps are flushed. This is to avoid the addition of concentrate(s) to the fluid stream until after the water has passed the pump(s) flushing channels. The first injection point j1 is also downstream of a recirculation valve V15, which is described below. When it comes to the downstream point, the concentrate fluid must be added at the first injection point j1 before it is measured by the sensor (e.g. conductivity cell), as the signal from the sensor is used to control the mixing. As there is a mixing chamber 17 to facilitate good mixing, the first injection point j1 may even be upstream of this component. The first dosing pump 11 is located on the first dosing line 10 and the control unit 19 controls it to circulate fluid in the first dosing line 10.

[0194] The second dosing line 15 puts the second concentrate access 12 into fluid communication with the main fluid line 3 at a second injection point j2 located between the inlet point 4 and the outlet point 5. More specifically, the second injection point j2 is located downstream of the water inlet valve V3 and the pressure regulator 41. Furthermore, in the embodiment of Figure 1 , the second injection point j2 is also located downstream of the flushing channels described above through which the pumps are flushed. This is to avoid the addition of concentrate(s) to the fluid stream until after the water has passed the pump(s) flushing channels. The second injection point j2 is also downstream of a recirculation valve V15, which is described below. When it comes to the downstream point, the concentrate fluid must be added at the second injection point j2 before it is measured by the sensor (e.g. conductivity cell), as the signal from the sensor is used to control the mixing. As there is a mixing chamber 17 to facilitate good mixing, the second injection point j2 may even be upstream of this component. The second dosing pump 16 is located on the second dosing line 15 and the control unit 19 controls it to circulate fluid in the second dosing line 15.

[0195] A first pressure sensor P1 operates between the pressure regulator 41 and the main fluid pump 6; in the disclosed embodiment, the first pressure sensor P1 is located between the first injection point j1 and the second injection point j2 to sense the pressure regimen in the main fluid line 3.

[0196] A pre-mixing mixing chamber 20 (also called secondary mixing chamber) is placed on the main fluid line 3 and located downstream of the first injection point j1 and the second injection point j2 and upstream of a main mixing chamber 17. The purpose of the pre-mixing mixing chamber 20 is to compensate for the large concentration differences downstream of the first and second injection points j1 , j2. It allows an improved mixing and a stable measurement of a property, e.g., conductivity of the fluid flowing in the main fluid line 3. The pre-mixing mixing chamber 20 may or may not be required.

[0197] A heater 21 for heating the fluid flowing in the main fluid line 3 is placed just upstream of or downstream of the pre-mixing chamber 20 (and consequently downstream of the first injection point j1and the second injection point j2). In the disclosed embodiment the heater 21 is placed downstream of the pre-mixing chamber 20 to avoid heating an unmixed solution, where e.g., a local high concentration of glucose may occur.

[0198] The heater 21 is also placed upstream of the mixing chamber 17 and upstream of the main pump 6 acting on the main fluid line 3. An inlet temperature sensor T 1 senses a temperature of the fluid flowing in the main fluid line 3 immediately upstream of the heater 21, while an outlet temperature sensor T2 senses a temperature of the fluid flowing in the main fluid line 3 immediately downstream of the heater 21. In an embodiment, the control unit 19 controls the heater 21 based on the temperature measured by the outlet temperature sensor T2, and possibly also based on the inlet temperature sensor T 1 (feedforward). The feed-forward control mechanism anticipates changes in the heating requirement based on the temperature value measured by sensor T 1 , rather than just reacting to the current outlet temperature. Feedforward control is a proactive approach that may improve the apparatus responsiveness. At the same time, the inlet temperature sensor T1 may sense the temperature in the coldest point in the fluid circuit 2 during heat disinfection and optionally provide a feed-forward response to the control unit 19, to control the operation of the heater 21. Sensing the temperature at the assumed coldest point allows the heater to be controlled to heat the disinfectant fluid to the correct temperature to allow complete disinfection of the fluid circuit 2 and also to use e.g. AO or equivalent disinfection method, thereby minimizing and / or reducing the energy and time required for disinfection.

[0199] Notably, the control unit 19 is configured to control the heater 21 to raise the temperature of the fluid flowing in the main fluid line 3 to a temperature of at least 30°C and more specifically up to at least 37°C during operation of the apparatus while preparing and / or delivering the medical fluid. The temperature control to a set temperature (e.g., 37° - usually higher than the ambient temperature) may improve the conductivity measurements as the reading property of the sensor is optimized to such a temperature.

[0200] The main mixing chamber 17 is placed on the main fluid line 3 and located downstream of the first injection point j1 and the second injection point j2 and upstream of the outlet point 5. It comprises a mixing chamber inlet 17a to receive fluid from the main fluid line 3 and a mixing chamber outlet 17b to release properly mixed fluid to the main fluid line 3 downstream of the mixing chamber 17 itself. The mixing chamber 17 achieves the optimized mixing of the water and the concentrates injected at the first injection point j1 and / or at the second injection point j2. Normally, the mixing chamber 17 is located downstream of the heater 21 in order to catch any air bubbles that may be generated when heating a fluid.

[0201] A relevant component of the fluid circuit 2 is the main pump 6, which operates to pump fluid throughout the main fluid line 3. Positioned downstream of the first injection point j1, the second injection point j2, and the mixing chamber 17, the main pump 6 is controlled by the control unit 19 and ensures proper fluid movement and circulation within the fluid circuit 2. Main pump 6 is controlled to push the fluid inside the main fluid line along the same direction from the injection points j1 and j2 towards the outlet point 5. Pump6 does not need to be driven in the reverse direction (i.e., fluid flow directed from the pump 6 towards the injection points j1, j2), nor does it allow such a fluid flow. In other embodiments, the main pump 6 may run in both directions.

[0202] A presence-of-flow sensor 42 for detecting presence of a fluid flow in the main fluid line 3 is also present on the main fluid line 3. For example, the presence-of-flow sensor 42 may be a pressure sensor P3 configured to detect a pulsation flow in the main fluid line 3. The pressure sensor P3 is located on the main fluid line 3 in close proximity, namely immediately upstream or downstream, of the main pump 6. The control unit 19 is configured to activate the heater 21 exclusively if the presence-of-flow sensor 42 detects the presence of a fluid flow in the main line 3.

[0203] At least one sensor, and particularly two sensors 18, 31, are configured to measure a property of the fluid flowing in the main fluid line 3. In general, the sensor / s 18, 31 may measure any one of a conductivity of the fluid, a concentration of a substance in the fluid, a concentration dependent physical properties, such as sound velocity, viscosity, density, a temperature of the fluid, and an optical property of the fluid flowing in the main fluid line 3 (and combinations thereof). For example, sensor 18 and / or sensor 31 may be a conductivity sensor, a concentration sensor, a temperature sensor, an optical sensor, a viscosity sensor, a density sensor, or a sound sensor.

[0204] In a specific embodiment, the sensor comprises a first conductivity meter 18, and a second conductivity meter 31 , too; preferably the two conductivity meters are positioned in series with each other during some operations of the apparatus as will be clarified in the following.

[0205] The first conductivity meter 18 is configured to determine a conductivity of the fluid or the fluids circulating in the medical fluid generation apparatus 1. The second conductivity meter 31 is configured to independently determine the conductivity of the fluid or the fluids circulating in the medical fluid generation apparatus 1 . Both the first conductivity meter 18 and the second conductivity meter 31 determine and detect the conductivity of the same fluid flowing along the main fluid line 3 (or flowed along the main line 3) to provide a back-up measure. Usually, one of the two sensors 18, 31 is controlled by a controller of the control unit 19 and the other one of the two sensors 18, 31 is controlled by a supervisor of the control unit 19 as known in the art. For example, in the embodiment according to figure 1 sensor 18 belongs to the protective / supervisory system while sensor 31 belongs to the control system. In figure 2 each of the sensors 18, 31 may belong to either of the protective system or the control system.

[0206] A temperature sensor T3 is also present in the main fluid line 3; usually, but not necessarily, the temperature sensor T3 is incorporated in the conductivity meter 18 and provides a temperature signal to the control unit 19. The temperature signal is used to compensate the raw conductivity value. This allows the fluid temperature to vary (within established / allowed limits) while the compensated conductivity reading is still comparable to references. Since two conductivity meters are provided, two temperature sensors T3 and T4 are also provided. Of course, the temperature sensor(s) T3 and / or T4 may be sensor(s) separated from other components (i.e., independent components measuring the temperatureof the fluid flowing in the main fluid line 3 at different locations, usually in respective close proximity to the respective sensor 18, 31).

[0207] The heater 21 is managed by the control unit 19, which is appropriately configured to handle the signals and data sent to and received from the heater 21 and the conductivity meters. The temperature sensors T3 and / or T4 provide their readings directly to the control unit 19. Downstream of the first sensor 18, a diverting valve V13 is interposed between the main fluid line 3 and an evacuation line 40 fluidly connecting the main fluid line 3 to a drain 27; the diverting valve V13 is part of the plurality of valves and is controlled to selectively prevent or allow fluid to flow from the main fluid line 3 into the evacuation line 40. The evacuation line 40 and the diverting valve V13 are used to direct the mixed solution to drain 27 during composition / temperature stabilization as apparent from the description of the operation of the apparatus 1 . As represented in figure 1 , the diverting valve V13 is located on the main fluid line 3; the control unit 19 switches the diverting valve V13 from a first operating condition permitting a fluid flow along the main fluid line 3 (i.e., the fluid flow crosses valve V13 and moves along the main fluid line 3) and preventing a fluid flow along the evacuation line 40, and a second operating condition permitting a fluid flow from the main fluid line 3 upstream of the diverting valve V13 to and along the evacuation line 40 and preventing a fluid flow from the main fluid line portion upstream of the diverting valve to a main fluid line portion downstream of the diverting valve.

[0208] Moving along the main fluid line 3, the fluid circuit 2 further comprises an air intake line 45 for allowing air to enter the main fluid line 3. The plurality of valves includes an air intake valve V4 located at the junction between the air intake line 45 and the main fluid line 3 to define the fluid flow. The control unit 19 controls the air intake valve V4 to selectively open and close the air intake line 45. An air filter 46 is provided on the air intake line 45 to filter the air entering the main fluid line 3. The air filter 46 is a bacteria retaining filter to keep the intake air sterile when performing an integrity test of the filter(s) 24, 26.

[0209] A first filter 24 is provided downstream of the sensor 18 and downstream of the air intake line 45. In particular the first filter 24 is an ultrafilter, which is intended to reduce any microbial contamination prior to fluid delivery to the external dialysis unit 23. As indicated, the filter 24 has a semipermeable membrane separating a filter volume into an inlet chamber and an outlet chamber, an inlet 24a connected to the main fluid line 3 for receiving fluid from the main fluid line 3, an outlet 24b connected to the main fluid line 3 for delivering filtered fluid to the main fluid line 3, and an auxiliary outlet 24c. The outlet 24b is part of the outlet chamber, while the inlet 24a and the auxiliary outlet 24c are part of the inlet chamber. The medical fluid from the main fluid line 3 entering the filter through the inlet 24a leaves the filter through the outlet 24b after passing through the semipermeable membrane.

[0210] A filter flushing line 25 is provided which is connected to the auxiliary outlet 24c and is in fluid communication with a drain 27. The connection to the drain 27 is provided by the aforementioned evacuation line 40 to which the auxiliary outlet and the filter flushing line 25 are connected by a common line tract 25a. The plurality of valves includes a closure valve V10 on the filter flushing line 25 theopening / closing of which is controlled by the control unit 19 to selectively open and close the filter flushing line 25. The filter 24 is flushed to the drain 27 using the valve V10 and the filter flushing line 25 (of course also valves V11 , V12 and V14 are controlled in the open condition).

[0211] A second filter 26 in series with the first filter 24 on the main fluid line 3 is provided. Said second filter 26 is downstream of the sensor 18 and downstream of the main pump 6. The second filter 26 may be an ultrafilter, too and aims at further reducing any microbial contamination before fluid delivery to the external dialysis unit 23. It provides a second safety barrier against microbial contamination.

[0212] A connecting tract 29 of the main fluid line 3 is interposed between the first filter 24 and the second filter 26 and connects the outlet 24b of the filter 24 to an inlet 26a of the second filter 26; a valve V9 is interposed between the outlet 24b of the filter 24 and the inlet 26a of the second filter 26 to selectively prevent or allow a fluid flow.

[0213] Correspondingly to the first filter, also the second filter 26 has a semipermeable membrane separating the filter into an inlet chamber and an outlet chamber, the inlet 26a connected to the connecting tract 29 for receiving fluid from the main fluid line 3, an outlet 26b connected to the main fluid line 3 for feeding filtered fluid to the main fluid line 3, and an auxiliary outlet 26c. The outlet 26b is part of the outlet chamber, while the inlet 26a and the auxiliary outlet 26c are part of the inlet chamber. The medical fluid from the main fluid line 3 entering the filter through the inlet 26a leaves the filter through the outlet 26b after passing through the semipermeable membrane.

[0214] A second flushing line 28 is connected to the auxiliary outlet 26c of the second filter 26 and is in fluid communication with the drain 27, particularly through the evacuation line 40. Valve V11 is active on the second flushing line 28 and the control unit 19 controls the valve V1 1 to selectively open and close the second flushing line 28. Notably, the second filter 26 is flushed to drain 27 using the valve V11 and the second flushing line 28.

[0215] Although Figure 1 shows two filters, in an alternative embodiment only one filter (or more than two filters) may be implemented. In case one filter is adopted, a sterile filter on the external line to the receiving part may or may not be added.

[0216] As apparent from figure 1 , the second conductivity sensor 31 is provided at the evacuation line 40 downstream of the first and the second filter 24, 26 via a bypass line 33 (and closure valve V7) to sense the conductivity of the fluid prior to delivery to the dialysis unit 23. In case the first and / or second filter 24, 26 is filled with fluid having a composition that differs from a target composition (e.g., water or wrong first and / or second concentrate concentration), the fluid needs to be flushed out to the drain 27 until the conductivity is sufficiently close to the target and / or to the conductivity measured by the first conductivity sensor 18.

[0217] As represented, though not limiting the present embodiment, the filter flushing line 25 and the second flushing line 28 share the common line tract 25a that in turn is in direct fluid communication with the evacuation line 40 and the drain 27. In this regard, the plurality of valves includes a shut valve V14located on the common line tract 25a and the control unit 19 controls the shut valve V14 to selectively open and close the common line tract 25a.

[0218] Furthermore, the main fluid line 3 comprises a delivery tract 30 interposed between the second filter 26 and the outlet point 5. A delivery line pressure sensor P2 is provided in the delivery tract 30 to measure a pressure of the fluid flowing therein before or during delivery of the medical fluid to the external device.

[0219] In addition, the plurality of valves comprises a delivery valve V8 on the delivery tract 30 interposed between the outlet 26b of the second filter 26 and the outlet point 5 to selectively prevent or allow the fluid flow.

[0220] The bypass conduit 33 fluidly connects the delivery tract 30 to the drain 27, again through the evacuation line 40 and the closure valve V7 is placed on the bypass conduit 33 to selectively prevent or allow a fluid flow therein. The bypass conduit 33 is directly connected to common line tract 25a in turn directly connected to the evacuation line 40. The delivery valve V8 located on the main fluid line 3 allows a fluid flow from the main fluid line 3 to the bypass conduit 33 and to selectively allow a fluid flow from the main fluid line tract upstream of the delivery valve V8 to a main fluid line tract downstream of the delivery valve V8 towards the outlet point 5. Notably the delivery valve V8 is located upstream of the closure valve V7 along a fluid flow direction during apparatus operation.

[0221] As visible in figure 1 showing the most effective embodiment, the fluid circuit 2 further includes a return conduit 38 connecting a return port 39, connectable to an external device, e.g., a dialysis unit 23, to the drain 27. The external device may be connected to the return port 39 and use it and the return conduit to discharge (spent) fluid to the drain.

[0222] The fluid circuit 2 also shows a water recirculation conduit 36 connecting a point of the main fluid line 3 upstream of the first injection point j1 and the second injection point j2 with an external point should it be necessary to send out water from the fluid circuit and the apparatus; in this regard, the plurality of valves comprises the recirculation valve V15 configured to selectively prevent or allow a fluid flow in the water recirculation conduit 36.

[0223] The fluid circuit of the second embodiment - Figure 2

[0224] Figure 2 shows a schematic view of a second embodiment of a fluid circuit of the present description. The same reference numbers have been used to identify the same components. In the following paragraphs, this second embodiment is described, specifically with regard to the differences or alternative arrangements compared to the embodiment of figure 1. Where appropriate, the same description and technical details of the embodiment of figure 1 apply to the apparatus 1 of figure 2.

[0225] Pure water is supplied to the fluid circuit 2 via entrance 39. For example, an independent water purification equipment 22 is used to purify the water prior to delivery to the apparatus.

[0226] The main fluid line 3 is highlighted with a double line in figure 2 for ease of understanding the water and solution liquid path.

[0227] Water from the inlet point 4 passes through the water inlet valve V3 and arrives at the first and second injection point j1, j2 before reaching the pre-mixing chamber 20. For the same reasons previously explained, the water is directed to flush the main pump 6 and the first and second dosing pumps 11 and 16, prior to receiving the liquid concentrates from the two dosing lines 10 and 15.

[0228] The main pump 6 of figure 2 embodiment is placed immediately downstream the premixing chamber 20. The position of the main pump 6 relative to the other described components on the main fluid line 3 may be different, and for example may correspond to the position in the embodiment of figure 1 . It is also possible to place the main pump 6 upstream the first injection points j1 and / or the second injection point j2, or even downstream the first sensor 18. Similar considerations are also valid in respect to the embodiment of figure 1 , where the main pump location may be changed without departing from the invention.

[0229] The heater 21 together with respective inlet and outlet temperature sensors T 1 and T2 follows the main pump 6 along the main line 3 and is upstream of the mixing chamber 17. The mixing chamber 17 has the service line 35; 32 connected to its top portion and directs fluid, gas or a combination of fluid and gas to the evacuation line 40 and to the drain 27. Valve V6’ is used to selectively open the service line 35.

[0230] The first and second sensors 18, 31 and their respective temperature sensors T3, T4 are placed in series along the main fluid line 3 to read the property of the mixed solution (e.g., concentration or conductivity) in sequence while flowing along the main fluid line 3. This is a different arrangement of the sensors with respect to the embodiment of figure 1 , still within the scope of the invention.

[0231] Two filters 24, 26, one or both being ultrafilters, are arranged in series downstream of the first and second sensors 18, 31 similar to the embodiment of figure 1 . Differently, two pressure sensors PUI1 and PUI2 are placed at the inlet of each respective filter 24, 26. Further, closure valve V11 is placed directly on the second flushing line 28 upstream the common tract shared by the flushing lines of the two filters.

[0232] A third sensor 54 may be present downstream of the filter(s) 24, 26. The third sensor 54 may be a conductivity sensor or a concentration sensor (e.g., sodium ion sensor) or a sensor of a different kind. During medical fluid preparation, the mixed solution passes the (ultra)filter(s) located downstream first and second sensors 18, 31 to ensure that the medical fluid to be delivered to the external device meets the microbial control requirements. If the third sensor 54 is a conductivity sensor, it is located downstream of the filter 26 to sense the conductivity of the fluid that is going to be delivered to the external device, e.g., the dialysis unit. Alternatively, a sensor to keep track of the composition of the fluid may be used. The third sensor 54 may be used to ensure that the fluid composition downstream of the filter(s) is substantially the same as that upstream of the filter(s) before it is sent to the outlet port 5. Flushing to drain 27 is achieved by controlling the delivery valve V8 to the closed condition, the closure valve V7 on the bypass conduit 33 to the open condition, valve V12 on the evacuation line 40 to the open condition and maintaining in theclosed position the other relevant valves on the fluid path to drain, such as closure valve V5 on the recirculation conduit 34 and discharge valve V6’ on the service line 35 from the mixing chamber 17.

[0233] The main fluid line 3 includes the delivery tract 30 flowing the medical fluid to the outlet port 5 and delivery valve V8 allows or prevent medical fluid to pass on command by the control unit 19.

[0234] Return conduit 38 with its entrance 39 is also present and is fluidly connected to the evacuation line 40 via common tract 25a of the flushing lines 25, 28. A closure valve V16 is located on the return conduit 38 for selective fluid passage.

[0235] An auxiliary recirculation conduit 36’ is included in the fluid circuit 2 of the embodiment represented in figure 2. The auxiliary recirculation conduit 36’ connects a portion of the main fluid line 3 upstream of the first and second injection points j1 , j2 and particularly also upstream the water inlet valve V3, to a portion of the main fluid line 3 downstream of the at least one sensor 18, 31; the auxiliary recirculation conduit 36’ second end is in particular fluidly connected to the main fluid line between the sensor 18; 31 and the filter 24; 26. Additionally, the auxiliary recirculation conduit 36’ is also fluidly connected to the second dosing line 15 as illustrated in figure 2. One or more closure valves V17, V18 may be located on the auxiliary recirculation conduit 36’ to allow or prevent water flow. More in detail, one closure valve V17 is located upstream of the connection point to the second dosing line 15, while the other closure valve V18 is located downstream of the connection point to the second dosing line 15.

[0236] An accessory 55 for connecting the concentrate accesses 7, 12 may be used in order to create a fluid connection between these ports to be used during e.g., circuit disinfection. The accessory allows fluid flow between the first and second concentrate accesses 1 , 12.

[0237] A comparison between figure 1 and 2 shows that placing one sensor in a line different from the main fluid line 3 (for example in the evacuation line 40) may allow to reduce the number of sensors to check correctness of the medical fluid flowing in the fluid circuit. Indeed, both during concentrate mixing and during flushing of filter(s) the medical fluid composition may be properly monitored. In the embodiment of figure 2, an additional sensor 54 is used to check when the fluid out of the filter(s) 24, 26 has proper conductivity / composition.

[0238] Further, the specific position of the main pump 6 on the main fluid line 3 may be changed. Indeed, in any of the two embodiments, the main pump 6 could be placed upstream of the injection points j1, j2. This specific positioning would require a change in the control of the main pump flow rate as the dosing pumps 11 , 16 will then inject liquid concentrate downstream the main pump, thereby changing (increasing) the flow rate along the main fluid line 3. The main pump 6 may also be placed downstream of the injection points j1 , j2 and upstream the pre-mixing chamber 20 or immediately downstream of this component. The main pump 6 may also be located downstream of the mixing chamber 17 (as illustrated in figure 1). Any of these positioning is feasible for both described embodiments. Though not strictly necessary, the main pump 6 would normally be placed upstream of the sensor 18, 31 .

[0239] The fluid circuit of the third embodiment - Figure 3

[0240] Figure 3 shows a further embodiment of fluid circuit according to the present description.The representation of figure 3 is schematic; same reference numbers have been maintained to identify components or lines / conduit that are also present in figure 1 or 2. Where not differently indicated, the same technical features and considerations applicable to the other two embodiments, also apply to the embodiment of figure 3.

[0241] The main difference between the embodiment of figure 3 and the embodiments of figures 1 and 2 is the presence of two ports for each concentrate container. Indeed, the first concentrate container 9 is connected to the supporting structure at first concentrate access 7 and at first concentrate auxiliary access 50. Correspondingly, the first concentrate container 9 has respective port 8 and auxiliary port 51 . Two concentrate accesses 7, 50 may be necessary if the first concentrate F is a dry concentrate that requires to be dissolved prior to dilution to form the medical solution. Therefore, a recirculation circuit may be provided to allow proper dissolution and homogenization of the concentrate. In other terms, one access is used as inlet for water to the first container and the other access is used as outlet from the container to allow for fluid re-circulation through the first container 9. Further, a filter 56 is present in the line connecting the second port 51 to the first concentrate auxiliary access 50 to prevent foreign elements (e.g., granulate) from reaching internal components of the apparatus.

[0242] The second concentrate container 14 is connected to the supporting structure 37 at second concentrate access 12 and at second concentrate auxiliary access 52. Correspondingly, the second concentrate container 14 has respective port 13 and auxiliary port 53. Two concentrate accesses 12, 52 may be necessary if the second concentrate S is a dry concentrate that requires to be dissolved prior to dilution to form the medical solution. Therefore, a recirculation circuit may be provided to allow proper dissolution and homogenization of the concentrate. In other terms, one access is used as inlet for water to the second container and the other access is used as outlet from the container to allow for fluid re-circulation through the second container 14. Further, a filter 57 is present in the line connecting the second port 53 to the second concentrate auxiliary access 52 to prevent foreign elements (e.g., granulate) from reaching internal components of the apparatus.

[0243] Of course, the apparatus of figure 3 may receive also liquid concentrates with only one port. In this case only one respective concentrate access is used to receive the liquid concentrate from the container. A combination of a dry concentrate (requiring two concentrate accesses) and a liquid concentrate (requiring one concentrate access) is possible, too. Notably, the embodiments of figures 1 and 2 may be configured to have additional accesses for the concentrates and recirculation lines to manage also one or more dry concentrates.

[0244] Back to figure 3, pure water enters the supporting structure 37 at entrance 39 and pass through the water inlet valve V3. A closure valve V19 is located between the first injection point j1 and the second injection point j2 to close the main fluid line 3 during recirculation to dissolve a dry concentrate. The main pump 6 is located downstream of the second injection point j2 and immediately upstream the mixingchamber 17. Note that no pre-mixing mixing chamber is present in this embodiment. The same can be for the embodiments of figures 1 and 2. At the outlet 17b of the mixing chamber 17, the heater 21 is provided.

[0245] One or more sensors 18, 31 of the same nature of the sensors of figures 1 and 2 are provided. The two sensors with their corresponding temperature sensors T3 and T4 are placed in series to one another.

[0246] The medical fluid reaches the delivery tract 30 after passing the sensor(s) to reach the outlet port 5 after passing delivery valve V8. An evacuation line 40 is connected to the main fluid line 3 just upstream the delivery tract 30 and its closure valve V12 allows selective passage to drain 27. No filters are present in the embodiment of figure 3; of course one or two filters may be added upstream of the outlet port similar to the previous embodiments. Alternatively, a filtration may be provided downstream of the outlet port 5 in the line connecting to the external device.

[0247] From the top of the mixing chamber 17 a mixing chamber discharge conduit 32 brings eventual air to the evacuation conduit 40. Discharge valve V6’ allows selective discharge via discharge conduit 32.

[0248] As shown in figure 3, the first dosing line 10 connects the first concentrate access 7 with the main fluid line 3 at junction point j1. The first dosing pump 11 being located on the first dosing line 10 downstream of a dosing line intermediate point 10a. An auxiliary line 58 fluidly connects the first concentrate auxiliary access 50 to the first injection point j1 . A closure valve V20 is located on the auxiliary line 58.

[0249] Correspondingly, the second dosing line 15 connects the second concentrate access 12 with the main fluid line 3 at junction point j2. The second dosing pump 16 being located on the second dosing line 15 downstream of a dosing line intermediate point 15a. An auxiliary line 59 fluidly connects the second concentrate auxiliary access 52 to the second injection point j2. A closure valve V21 is located on the auxiliary line 59.

[0250] The fluid circuit 2 further comprises a return line 60 connected to the main fluid line at a third junction point j3 which is positioned downstream of the sensor(s) 18, 31. The return line 60 is fluidly connected to the first dosing line 10 at the dosing line intermediate point 10a. A branch line 60a branches off from the return line 60 at a branch point 60b and is fluidly connected to the second dosing line 15 at the dosing line intermediate point 15a.

[0251] A valve V22 is located on the return line 60, specifically between the branch point 60b and the dosing line intermediate point 10a to selectively block the fluid flow towards the first dosing line 10. Another valve V23 is located on the branch line 60a to selectively block the fluid flow towards the second dosing line 15.

[0252] Dissolution Sequence

[0253] As previously discussed, the apparatus of the described embodiments may use liquid concentrates and / or dry concentrates.

[0254] In case only liquid concentrates are used, there is no need to perform a dissolution procedure and the mixing sequence as described in the following sections may be immediately started.

[0255] Vice versa, in case one or more dry concentrates are used, before starting the mixing sequence, the dry composition inside the concentrate container(s) may need to be dissolved in water prior to mixing to form a liquid concentrate that is homogeneous in composition.

[0256] Reference is now made to the embodiment of figure 3 showing the use of two dry concentrates. The first step is to dissolve the powder concentrates into liquid concentrates that have a concentration allowing final mixing to a composition within the requirements for the medical fluid, for example dialysis liquid.

[0257] The dissolution procedure comprises filling each concentrate container 9, 14 containing the powder vol u metrical ly with a nominal amount of water using the main pump 6. The term "nominal" here indicates that it is a set value used as a reference; the nominal value may be based on the specific container used and / or on its dry concentrate content. The filling may be performed in sequence or simultaneously. In case the concentrate containers 9, 14 are filled simultaneously to speed up the filling process, the first and second concentrate pumps 11, 16 could be switched on during the filling process. In this process, for example, the first concentrate container 9 is filled by both main pump 6 and first dosing pump 11, while the first phase of filling the second concentrate container 14 is done by second dosing pump 16. As soon as the first concentrate container 9 has reached its volume, the main pump 6 continues to operate helping the second dosing pump 16 to complete the filling of the second concentrate container 14. Typically, either or both the containers are filled by feeding water to a respective lower connection (e.g., ports 8 and 13) so that each container is filled from below.

[0258] During the filling phase, the control unit 19 heats the water to a specified initial temperature using the heater 21 . An initial dissolution of the dry concentrate takes place.

[0259] Thereafter, the control unit 19 runs a subsequent dissolution step to complete dissolution of the first and the second concentrates F, S more preferably, but not necessarily, in parallel.

[0260] The control unit 19 recirculates in a closed loop the first concentrate F by opening valve V20 and operating the first dosing pump 11, for example backwards. Closure valve V22, water inlet valve V3 and closure valve V19 are closed to allow the recirculation of the fluid only in the loop including the first dosing line 10, the first concentrate container 9 and the auxiliary line 58.

[0261] At the same time (or if desired before or after the recirculation of the first concentrate F) the control unit 19 is also configured to recirculate in a closed loop the second concentrate S by opening valve V21 and valve V23 and operating the main pump 6. In this case the recirculation loop includes a portion of the main fluid line 3, where the main pump is located, up to the third junction point j3, the return line 60 up to the branch point 60b, the branch line 60a, the portion of the second dosing line 15 from the intermediate point 15a up to the second concentrate access 12, the second concentrate container 14 andthe auxiliary line 59 up to the second injection point j2. The apparatus controls the fluid temperature during dissolution of the second concentrate S with the heater 21 and one of the temperature sensors T3, T4.

[0262] Alternatively, the recirculation loop for the dissolution of the second concentrate S may be defined by the second dosing line 15, the auxiliary line 59, and the second concentrate container 14. In this case, valve V21 is in the open configuration, while closure valve V23 is in the close configuration and the fluid is recirculated by the second dosing pump 16.

[0263] As a further alternative, dissolution of the first concentrate F may be achieved by recirculating the first concentrate F via the main pump 6. In this case, valve V20, V22 and V19 are in the open configuration. The recirculation loop includes a portion of the main fluid line 3 from the first injection point j1 to the third junction point j3, the return line 60 up to the intermediate point 10a of the first dosing line 10, the portion of the first dosing line 10 up to the first concentrate access 7, the first concentrate container 9 and the auxiliary line 58. During dissolution of the first concentrate F, valves V3 and V23 are closed. The apparatus controls the fluid temperature during dissolution of the first concentrate F with the heater 21 and one of the temperature sensors T3, T4.

[0264] A concentration (e.g., glucose) sensor 62 may be used to monitor the second concentrate (e.g., glucose) dissolution process by measuring the substance concentration over time. A stable concentration indicates complete dissolution and uniform concentration. Correspondingly, a range extended conductivity cell may provide dissolution feedback for the first concentrate F. In alternative or in combination, the heat power profile of the solution during the respective dissolution process may provide dissolution feedback.

[0265] A further alternative variant is that, assuming that the first concentrate 9 contains electrolytes, once this dissolution is complete and homogeneous, the process may comprise having the apparatus add a quantity of the first concentrate to the loop of the second concentrate, which can contain glucose. Then, the second concentrate will also be conductive and the conductivity sensor may be used to determine when the second concentrate is dissolved and homogeneous. As the proportions of the added ingredients of the first concentrate are exactly the same in the second concentrate (although diluted), the apparatus can compensate for the added proportion in the production of the final medical fluid.

[0266] Moreover, during recirculation using the main pump 6, the corresponding dosing pump 11 ; 16 may be run in parallel to increase the recirculation flow.

[0267] During filling using the main pump 6, the corresponding dosing pump 11; 16 may further recirculate air. This may help avoid channeling.

[0268] Additional filter(s) may be provided also at the ports 8, 13 of the concentrate containers 9, 14 since these ports are the outlet during dosing to mixing.

[0269] Mixing Sequence Schedule Overview

[0270] After providing a detailed description of the fluid circuits according to the embodiments of figures 1 to 3 and of the dissolution procedure (if required), a description of the sequence to obtain the medical fluid will be discussed hereinafter.

[0271] The medical fluid generation apparatus aims to prepare a medical fluid from tap or purified water and concentrates, particularly, but not necessarily, liquid concentrates. The apparatus is configured to prepare the medical fluid “online”, namely the medical fluid is produced and delivered for upon the external device (e.g., dialysis unit) request. In other terms, the mixing of water and concentrates is performed on demand each time some medical fluid is required.

[0272] The medical fluid is thus "mixed inline" during its preparation and delivery to the outlet port 5, i.e. water and liquid concentrates mix along the main fluid line 3 as it flows, and is immediately delivered to the external device. During medical fluid preparation, there is a continuous flow of fluid along the main fluid line 3.

[0273] In general terms, water is drawn from the water purification unit. The main pump 6 controls the main flow rate, while the dosing pumps 11 , 16 control the concentrate dosing, such as the electrolyte / buffer and glucose dosing. Looking at figure 1, the water and the concentrates are pre-mixed in the secondary chamber 20 to even out the large concentration differences present after the first and second injection points j1 , j2. The secondary chamber has a small size, e.g. a few ml such as 5-20ml (depending on the size of the apparatus and its performances). As a result, the medical fluid continuously entering the secondary chamber from the inlet and leaving the secondary chamber from the outlet can remain in the secondary chamber for a limited period of time.

[0274] The medical fluid is heated by heater 21 and homogeneously mixed in mixing chamber 17. Sensor 18 monitors the conductivity of the medical fluid, which flows through the filter 24 and the second filter 26 before reaching the outlet port 5 for delivery to the external device requesting the medical fluid.

[0275] The specific steps to achieve the desired medical fluid generation will be explained in detail in the following section of the description. Here-below, an example of a sequence schedule overview for a specific application in the peritoneal dialysis field is provided. Of course, the overview refers to the specifically identified application in which the external device is a PD cycler. In case the external device is a hemodialysis machine or a different device requiring the medical fluid, the sequences will be different and dedicated to the specific medical device / application.

[0276] Figure 4 shows the schematic timeline of a concentrate in-use period for PD applications. With in-use period is meant the complete time, from new to used up, under which an opened and attached concentrate is used, i.e. its complete life while attached to the machine. A new set of first and second concentrate containers F, S (e.g., the concentrate bags) are attached to the first and second concentrate accesses 7 and 12, respectively, prior to the first treatment (TMT 1) and are then used throughout the in-use period, namely until they are used up and replaced with new concentrates. In the figure, the subsequent treatments are indicated as TMT 2 to TMT 5; of course, the number of treatmentsequences may vary depending on the specific apparatus set-up and on the patient prescription. With the first and second concentrate containers attached, the medical fluid generation apparatus 1 (with the exception of the concentrate accesses 7, 12, the service lines 43 and 44, and first and second dosing lines 10, 15) is heat disinfected (HD) between each treatment. An extended heat disinfection (EHD) is performed after the concentrate containers 9, 14 have been detached after the last treatment. The EHD also includes the disinfection of the concentrate accesses 7, 12, the service lines 43 and 44, and of the first and second dosing lines 10, 15. HD and EHD may also include ultrafilter rinse and / or integrity test sequences for the filter 24 and / or the second filter 26.

[0277] Figure 4 also shows the schematic timeline of mixing related sequences occurring during treatments.

[0278] As it will be explained in the following section, the correct solution composition of the medical fluid is checked before the medical fluid is sent to the external device, e.g., the dialysis unit 23. Composition is checked by measuring a property of the medical fluid with one or more sensors. For example, the concentration of certain solutes may be measured using e.g., concentration and / or conductivity sensor(s). Controlling the composition with conductivity means that any deviation from the nominal water concentration of the concentrates is automatically compensated for by the mixing mechanism. A full conductivity-based pump speed ratio determination is likely to be required whenever the concentrates are changed (e.g., at the start of TMT 1) as the water concentration of the new concentrates is usually unknown. Manufacturing variability and water evaporation during storage are reasons of water concentration deviation from nominal. Due to the daily loss of water by evaporation during the in-use period when the over pouch barrier is not present, the same procedure (full conductivity-based pump speed ratio determination) may optionally be required prior to some or all first fill preparations of a treatment.

[0279] For mix / fill events other than those mentioned above, a kick start (using the stored pump speed settings) may be sufficient to reach the desired composition. However, the kick start may be followed by a conductivity check during which the medical fluid is sent to drain before delivery to the dialysis unit (e.g., the PD cycler) begins. The conductivity check may be carried out every new day and / or may be part of the function check of the apparatus where the conductivity cells are compared to determine that they are working properly and giving the same reading when the same fluid is passing through.

[0280] A full conductivity-based pump speed ratio determination sequence will consume more time and concentrate fluid while the kick start will consume little or no time and concentrate fluid. The frequency requirement for full conductivity-based pump speed ratio determination sequences and the overall strategy in general will therefore affect the overall average time and concentrate consumption per treatment.

[0281] In general terms, and as illustrated in Figure 4, the first treatment (TMT 1) requires a pump speed ratio determination sequence that is typically run only once per concentrate in-use period. Then, if the dialysis unit is a PD cycler, a medical fluid mixing and the patient filling occur, followed by dwell in the patient’s peritoneum. Somewhere between the time when the first fill has been delivered and when ithas dwelled and drained from the patient, a mix kick start phase is required followed by mixing, filling, and dwell steps i.e., the apparatus is not waiting until the patient is drained before preparing the new fluid. In a different embodiment, the mix kick start may occur after the spent fluid has been drained from the patient. The determined pump speed ratios are then used during the mix kick start phase and during main flow changes in the apparatus due to the fluid requests from the dialysis unit.

[0282] The mix kick start phase followed by the mix, fill, and dwell steps is normally used during any one of the following treatments (TMT 2 to TMT 5) until the concentrate containers 9, 14 are changed. Real time conductivity monitoring and drift compensation for water loss is also performed during the next treatments TMT 2 to TMT 5.

[0283] Mixing Sequence

[0284] As previously indicated, the medical fluid generation apparatus is configured for on-line preparation of medical fluid by executing a medical fluid preparation procedure 1002 (see the flow chart of figure 7 reporting the various steps of the procedure). A non-limiting use of the described apparatus 1 is for the preparation of peritoneal dialysis fluid (PD fluid). The medical fluid will be prepared by mixing concentrates with pure water upon request from the external device, such as the dialysis unit 23.

[0285] The medical fluid delivery depends on the circumstances. If a set of bags has to be filled with the medical fluid, the online mixing is started upon request. Alternatively, during an Automated Peritoneal Dialysis (APD) treatment with a connected cycler, the operation of the apparatus depends on the cycler requirements. As above discussed, in one case, the medical fluid may be prepared at any time during the dwell phase (between the filling and the draining phases). In another situation, i.e., with a different cycler, the online mixing apparatus operates intermittently to supply PD fluid to the cycler during the filling phases. This means that the mixing apparatus is mostly on standby during the treatment and only produces PD fluid any time during filling and dwelling phases or during the fill phases (typically 10-15 minutes). Any mixing sequences performed prior to the first fill may add to the total time to / of treatment, depending on the duration of any sequences that need to be performed by the other subsystems (such as water purification unit and dialysis unit) prior to the first fill. On the other hand, any mixing sequences performed prior to subsequent fills within a treatment will not add to the total time to / of treatment, as there is sufficient time available during the dwell to perform these tasks.

[0286] With reference to Figure 1 , the mixing sequence that is the medical fluid preparation procedure, is summarized as follows. At the start of the apparatus, particularly in case new first and second concentrate F, S are connected to the fluid circuit 2, water, such as tap water, is purified and the main fluid path 3 receives pure water at the inlet point 4. Water purification may occur either inside (e.g., Figure 1) or outside (e.g., Figure 2) of the medical fluid generation apparatus 1.

[0287] A first concentrate mixing sequence 1003 for properly metering the first concentrate F is performed. The control unit 19 operates (step 1005 - fig. 7) the main pump 6 and operates (step 1006 - fig. 7) the first dosing pump 11. During this first concentrate mixing sequence, the main pump 6 and the firstdosing pump 11 are regulated in order to achieve the proper mixing of water and first concentrate F, while the second dosing pump 16 is kept inactive (i.e., no flow occurs in the second dosing line 15). Pure water flows up the first injection point j1 , whereas a mixture of water and first concentrate F flows during fluid preparation downstream of injection point j1.

[0288] The main pump 6 controls the main flow rate while the first dosing pump 11 (concentrate pump) controls the first concentrate F (e.g., electrolyte / buffer) dosing. The control unit 19 receives (step 1007 - fig. 7) the signal from the sensor 18, 31. The first dosing pump 11 is in a first phase controlled (step 1008 —fig. 7) with a measure of a property of the fluid (e.g., conductivity) feedback from a (e.g., conductivity) sensor 18, 31 located downstream of the main pump 6 and the mixing chamber(s), namely secondary mixing chamber 20 and mixing chamber 17, to achieve a target composition of the mixed medical fluid. Specifically the control unit 19 controls the diverting valve V13 on the main fluid line 3 to send the mixed medical fluid to the evacuation line 40 where the conductivity sensor 31 operates. In other words, the control unit 19 sets a first mixing flow path for the fluid starting from the inlet point 4 and along the fluid main line 3 passing through the first injection point j1, the second injection point j2, the secondary mixing chamber 20, the heater 21 , the mixing chamber 17, the main pump 6, and the conductivity sensor 18, then at diverting valve V13 moving to the evacuation line 40 passing through the conductivity sensor 31 and past the (open) valve V13 to drain 27.

[0289] Once the correct dosing of the first concentrate F has been achieved, the speed ratio between the first dosing pump 11 and the main pump 6 is determined (step 1009 - fig. 7) and set and the second dosing pump 16 is started (step 1011 - fig. 7) to begin injecting the second concentrate S at the second injection point j2 into the mixture of water and first concentrate F. Again, the fluid circuit 2 is configured to direct the fluid mixture of water, first concentrate, and second concentrate towards the sensor 31 located in the evacuation line 40 which directs the mixed fluid to drain, until the property of the mixed fluid reaches a predefined target indicating that the medical fluid has been produced. In other words, the control unit 19 receives (step 1012 - fig. 7) the signals from the sensor 31 and control (step 1013 - fig. 7) the second dosing pump flow rate to achieve the desired medical fluid composition. Once the desired composition of the medical fluid is obtained, the control unit 19 determines (step 1014 - fig. 7) and stores the ratio between the flow rate of the second dosing pump 16 and the main pump 6.

[0290] During the mixing sequence, no mixed fluid flows through the filter 24 and the second filter 26 towards the outlet point 5.

[0291] In the first concentrate mixing sequence, the first concentrate F and water composition is first determined; in a second concentrate mixing sequence, the second concentrate S, first concentrate F and water composition is determined. In the context of the preparation of PD fluid (thus not limiting), the reason for this sequence is that an initial conductivity given by the electrolyte dosing is required to measure the (negative) conductivity response of glucose. The fluid mixed in the first concentrate mixing sequence is directed to drain and discharged.

[0292] After speed ratios of the main pump 6, the first dosing pump 11 , and the second dosing pump 16 have been determined to reach the target composition in the concentrate mixing sequences, these pumps 6, 11, 16 are in the delivery sequence controlled by keeping their speed ratio constant. The fluid production rate may thus be varied by controlling the speed of the main pump 6 while keeping the pump speed ratios constant (first and second dosing pump speeds varied by the same factor as the main pump). The medical fluid mixed during the delivery sequence may be delivered to the external device, e.g., dialysis unit 23, only when certain conductivity criteria are met before and / or after the filter(s) 24, 26.

[0293] As already explained, it might not be necessary to execute the first concentrate mixing sequence every time the mixing starts; if the pump speed ratios have been established with a given set of concentrates, mixing may be “kick started” using these pump speed ratios and only a conductivity check.

[0294] First Concentrate Mixing Sequence (1003)

[0295] During the first concentrate mixing sequence the control unit 19 is configured to control the plurality of valves to define a first mixing flow path comprising an initial portion 48 of the main fluid line 3 including (at least) the first injection point j1, the second injection point j2, the mixing chamber 17, the diverting point 47, and the evacuation line 40 fluidly routing the fluid towards the drain 27. The first mixing flow path is defined during execution of both the first concentrate mixing sequence and the second concentrate mixing sequence.

[0296] After defining the first mixing flow path, the control unit 19 is then configured to start operation of the main pump 6 to pump fluid in the main fluid line 3. Water flows to the first injection point j1. The control unit 19 is also configured to start operation of the first dosing pump 11 to inject first concentrate F from the first concentrate container 9 into the main fluid line 3 at the first injection point j1. The mixture of water and first concentrate F is pre-mixed in the secondary mixing chamber 20, heated by the heater 21, homogeneously mixed in the mixing chamber 17 and flowed through the first conductivity sensor 18; at diverting point 47, the mixture is directed to the evacuation line 40, where its property, such as conductivity, is measured by sensor 31 before delivery to drain 27.

[0297] Based on the signal from either first sensor 18 or second sensor 31, the control unit 19 regulates the speed of the first dosing pump 11 to bring the property of the mixture of water and first concentrate in the main fluid line 3 towards a first property-of-the-fluid target for a mixture of water and first concentrate (namely a first conductivity target which is in turn a target of desired concentration). The first property-of-the-fluid target is either an external input or a stored data for example received / stored after experimentally determining it. Alternatively, the first property-of-the-fluid target may be calculated based on nominal concentrations of the solutes in the first concentrate F and on conductivity equations for each of said solutes in the first concentrate F.

[0298] The first property-of-the-fluid target is considered achieved when the measured property fulfills a first criteria of having reached the first property-of-the-fluid target. For example, first criteria compriseverifying that the mixture of water and first concentrate is within a predefined range of the first property-of- the-fluid target, such as within 2%, in particular within 0.5% and for example within 0.2%.

[0299] The first property of the fluid may be conductivity of the fluid, a concentration of a substance in the fluid, a concentration dependent physical property, such as sound velocity, viscosity, density, a temperature of the fluid, and an optical property of the fluid and combinations thereof. Usually, conductivity sensor(s) is / are used and the relevant property to achieve is a specific concentration of a solute e.g., sodium in the mixture.

[0300] Regulation of the speed of the first dosing pump 11 to bring the property of the mixture of water and first concentrate in the main fluid line 3 towards a first property-of-the-fluid target is achieved by the control unit 19 controlling the first dosing pump flow rate based on a property feedback controller (e.g., a PID controller), and keeping the main pump flow rate substantially constant.

[0301] Once the first criteria is met, the control unit 19 operates the first dosing pump 11 and the main pump 6 at the determined ratio to allow the property of the mixture of water and first concentrate F to stabilize. Once the value is stabilized (for example after a pre-set time period), the control unit 19 calculates a statistical property, e.g., a filtered mean, of said property of the mixture of water and first concentrate and stores the statistical property as a reached first property for the mixture of water and first concentrate for later use.

[0302] In an example, the first concentrate F may contain electrolytes and may be used for producing dialysis fluid. In this case, as above explained, and with reference to Figure 5, the electrolyte composition control includes a first phase during which the electrolyte dosing rate is adjusted with conductivity feedback from sensor 31 , in the example a conductivity sensor, until the conductivity is sufficiently close to the first property-of-the-fluid target, namely the predetermined target conductivity for the electrolyte + water mixture. As explained, the target conductivity for the electrolyte + water mixture is calculated based on the nominal concentrations of the electrolyte concentrate components in the mixture and conductivity equations for each solute.

[0303] A PID controller is used to control the first dosing pump 11 with conductivity feedback until certain conductivity magnitude and stability criteria are met. The first dosing pump 11 to main pump 6 speed ratio is then locked and stored in memory, e.g., in the memory of the control unit 19. A stabilization phase follows with locked pump speed ratio in which the conductivity is allowed to stabilize without the first dosing pump controller being active. A filtered mean of the resulting conductivity is thereafter saved for later use as an electrolyte + water baseline for the buffer / glucose composition control step.

[0304] Figure 5 shows an example of the first dosing pump speed and actual electrolyte + water conductivity determination sequence. The pump speed is controlled with conductivity feedback until the dashed line to cause the conductivity to be close to the target conductivity. The feedback control stops at the dashed line and the speed ratio of first dosing pump 11 and main pump 6 is locked. The conductivity is thereafter allowed to stabilize, and a filtered mean of the conductivity is continuously calculated. After apredetermined stabilization time, the actual electrolyte + water (EW) conductivity is taken as the current filtered mean (t = 660s). The difference between the target and actual electrolyte + water (EW) conductivity was in this case about 0.01 mS / cm or 0.1 %.

[0305] Second Concentrate Mixing Sequence (1004)

[0306] The second concentrate mixing sequence is carried out after the first concentrate mixing sequence is run. During execution of the second concentrate mixing sequence, the control unit 19 operates the second dosing pump 16 to inject the second concentrate S from the second concentrate container 14 into the main fluid line 3 at the second injection point j2. The second concentrate S starts mixing with the mixture of water and first concentrate F.

[0307] When the second dosing pump 16 is started at the beginning of the second concentrate mixing sequence, the speed ratio between the first dosing pump 11 and the main pump 6 has already been determined and the two pumps are controlled at the determined ratio so that the mixture of water and first concentrate F (within which the second concentrate will start to mix) is close to or equal to the set target for the mixture property (e.g., set target of conductivity).

[0308] During execution of the second concentrate mixing sequence, the control unit 19 receives signals from the sensor 18; 31 relating to the property of the mixture of water, first concentrate F, and second concentrate S in the main fluid line 3 and controls by regulating the second dosing pump flow rate based on the received signals relating to the property of the mixture of water, first concentrate, and second concentrate in the main fluid line 3.

[0309] The fluid circuit 2 is maintained in the mixing flow path configuration, where, according to the configuration of figure 1, both the water inlet valve V3 and the recirculation valve V15 on the initial portion 48 of the main fluid line 3 are set in a configuration that allows water to flow along the initial portion 48; the discharge valve V6 downstream the mixing chamber 17 is set in a configuration that allows water to flow along the initial portion 48, too. The diverting valve V13 is set in a configuration that allows the fluid to flow from the initial portion 48 of the main fluid line 3 to the evacuation line 40 also preventing the fluid to flow from the initial portion 48 to a terminal portion 49 of the main fluid line 3 and the closure valve V12 on the evacuation line 40 allows the fluid to flow through the evacuation line 40 towards the drain 27.

[0310] The control unit 19 is configured to obtain a second property-of-the-fluid target for the mixture of water, first concentrate F, and second concentrate s. The control (regulation) of the second dosing pump flow rate comprises changing the second dosing pump flow rate while keeping constant the ratio of the first dosing pump flow rate and the main pump flow rate, to bring the property of the mixture of water, first concentrate, and second concentrate in the main fluid line 3 towards the second property-of-the-fluid target.

[0311] The control unit 19 continuously measures the property of the mixture of water, first concentrate F, and second concentrate S in the main fluid line 3 through the sensor 18, 31 and determines the second dosing pump flow rate when the measured property fulfills a second criteria of having reachedthe second conductivity target. Note that the second criteria may be coincident with the first criteria, namely the second criteria may comprise verifying that the mixture of water, first concentrate and second concentrate is within a predefined range of the second property-of-the-fluid target, such as within 2%, in particular within 0.5% and for example within 0.2%.

[0312] The control unit may receive the second property-of-the-fluid target as external input or as stored data (e.g., after experimentally determining it); alternatively, the control unit 19 may calculate the second property-of-the-fluid target for the mixture of water, first concentrate, and second concentrate based on a target concentration for the mixture of water, first concentrate, and second concentrate of at least one substance in the second concentrate (S). In particular based on the concentration of said substance in the finally mixed medical solution. In case of production of PD fluid, the substance is glucose and the second target conductivity for the water + electrolytes + glucose solution is calculated based on the target glucose concentration in the finally mixed PD fluid. In case the second concentrate includes only (or almost only) glucose, the second property-of-the-fluid target for the mixture of water, first concentrate, and second concentrate is lower than the first property-of-the-fluid target for the mixture of water and first concentrate. The water + electrolytes + glucose target conductivity is typically 0.35 - 1 .05mS / cm lower than the water + electrolytes target conductivity, depending on the target glucose concentration.

[0313] In a specific embodiment of the present disclosure, during execution of the second concentrate mixing sequence, the control unit controls the second dosing pump 16 at an overdose flow rate to inject an overdose of the second concentrate S into the main fluid line 3 and subsequently measures the property of the mixture of water, first concentrate, and second concentrate in the main fluid line 3. Then the control unit 19 reduces the overdose flow rate of the second dosing pump 16 based on the subsequently measured property of the mixture of water, first concentrate, and second concentrate and further based on a delta between the first property-of-the-fluid target and the second property-of-the-fluid target.

[0314] More specifically, the control unit (19) is configured to calculate a speed of the second dosing pump (16) based on the following formula:Target S response Locked S pump speed = Overdose S pump speed ■ - - -Overdose S response wherein:‘Locked S pump speed is the calculated speed of the second dosing pump (16);‘Overdose S pump speed is a set speed of the second dosing pump (16) to generate the overdose flow rate;‘Target S response' is the delta between the reached first property-of-the-fluid and the second property- of-the-fluid target;‘Overdose response' is an actual delta between the reached first property-of-the-fluid and a measured property of the mixture of water, first concentrate, and second concentrate after the generation of the overdose flow rate.

[0315] As in the case of the regulation of the first dosing pump 11 during execution of the first concentrate mixing sequence, when the second dosing pump 16 is regulated to achieve the second property of the fluid target, the control unit 19 is configured to control the second dosing pump flow rate based on a property feedback controller (e.g., PID controller), and to keep the main pump flow rate and the first dosing pump flow rate, or better the ratio thereof, substantially constant.

[0316] As previously suggested, the above second concentrate mixing sequence may be used to regulate the mixing of glucose in the water + electrolyte solution for the preparation of PD medical fluid. The glucose composition control is more challenging than the electrolyte composition control due to the weak conductivity response of glucose. Glucose is dosed with conductivity feedback, and it is then the conductivity-decreasing effect that is used for composition control.

[0317] With reference to figure 6, as in the case with the electrolyte dosing, where a target conductivity of the water + electrolyte (EW) solution is calculated, the second target conductivity for the water + electrolyte + glucose (EWG) solution is calculated based on the target glucose concentration in the finally mixed PD fluid. The EWG target conductivity is typically lower than the EW target conductivity. This difference is denoted ACondG.

[0318] Since the EW target conductivity is normally not reached exactly during the first mixing sequence, the EWG target conductivity is adjusted with the difference between the EW target conductivity and the reached EW conductivity. The adjusted EWG target conductivity is hereafter denoted EWGCA.

[0319] There are two main options for reaching the correct glucose concentration using conductivity feedback. One is conductivity feedback control of the second dosing pump 16 using a PID controller. The glucose dosing is thereby controlled to reach EWGCA target conductivity. Ideally, this also means that the glucose conductivity response is equal to ACondG.

[0320] The second option is glucose overdosing followed by speed downscaling of the second dosing pump 16 based on the ratio between ACondG and measured conductivity response resulting from glucose overdosing. The second option appears to have an improved conductivity signal-to-noise ratio compared to the direct control method of the first option.

[0321] Regardless of feedback mechanism, the sequence will include conductivity stabilization phases with criteria principally similar to those for the EW step that must be met before the speed ratio of the second dosing pump 16 and the main pump 6 can be locked and saved.

[0322] The overdosing method is further explained in Figure 6 that represents an overview of the electrolyte and glucose control steps performed to find the pump speed ratios that yields the correct fluid composition. The bottom panel shows the first and second dosing pump speeds and the upper panel shows the target conductivities and the actual conductivity. First, in the E step, the first concentrate (electrolytes) is dosed with conductivity feedback to reach the target conductivity of water and first concentrate (electrolytes). The speed of the first dosing pump 11 is thereafter locked and a stabilized conductivity value (reached first property for the mixture of water and first concentrate) is saved. Second, in the G step, thesecond concentrate (glucose) is overdosed and the conductivity response is measured. The speed of the second dosing pump 16 to lock is thereafter calculated per the formula below the plots. The magnitude of the overdosing is typically chosen to cause a glucose concentration of 4-10%.

[0323] Operation for medical fluid preparation and delivery

[0324] Once the pump speed ratios have been determined and locked as previously described, the speed of the main pump 6 may be varied with maintained composition control of first and second concentrate, for example glucose and electrolytes.

[0325] The control unit 19 controls the plurality of valves to define a medical fluid delivery flow path, where the fluid may flow along the whole main fluid path 3 from the inlet point 4 to the outlet point 5. To define the medical fluid delivery flow path, the water inlet valve V3, the recirculation valve V15, and the discharge valve V6 are set in a configuration that allows water to flow along the initial portion 48. The diverting valve V13 is set in a configuration that allows the medical fluid to flow from the initial portion 48 towards a terminal portion 49 of the main fluid line 3 and prevents the fluid to flow from the initial portion 48 of the main fluid line 3 to the evacuation line 40. The air intake valve V4, the closure valve V9, and the delivery valve V8 allow the medical fluid to flow along the terminal portion 49 up to the outlet point 5.

[0326] During a medical fluid delivery phase, pure water flows through the inlet point and towards the first injection points j1 , j2 and the medical fluid, for example a dialysis treatment fluid, flows out of the outlet point 5.

[0327] The types of speed transients of the main pump 6 are mainly:• the mixing “kick start”: from standby, the apparatus may start the medical fluid production and start the delivery to the external device immediately when the medical fluid is required;• the main flow step changes; and• the gradual main flow changes resulting from pressure controlled operation of the main pump 6 as a part of the external device interface.

Claims

CLAIMS1. A medical fluid generation apparatus (1) comprising: a fluid circuit (2) including a main fluid line (3) developing between an inlet point (4) for receiving water and an outlet point (5) connectable to a treatment medical device, a main pump (6) located on the main fluid line (3) to pump fluid at least in the main fluid line (3), wherein the fluid circuit (2) further includes: o a first concentrate access (7) fluidly connectable to a port (8) of a first concentrate container (9) containing a first concentrate (F), o a first dosing line (10) putting in fluid communication the first concentrate access (7) and the main fluid line (3) at a first injection point (j1) located between the inlet point (4) and the outlet point (5), o a second concentrate access (12) fluidly connectable to a port (13) of a second concentrate container (14) containing a second concentrate (S), o a second dosing line (15) putting in fluid communication the second concentrate access (12) and the main fluid line (3) at a second injection point (j2) located between the inlet point (4) and the outlet point (5); o a mixing chamber (17) placed on the main fluid line (3) and located downstream the first injection point (j1) and the second injection point (j2) and upstream the outlet point (5), the mixing chamber (17) comprising a mixing chamber inlet (17a) configured to receive fluid from the main fluid line (3) and a mixing chamber outlet (17b) configured to release fluid to the main fluid line (3), a first dosing pump (11) configured to pump fluid in the first dosing line (10), a second dosing pump (16) configured to pump fluid in the second dosing line (15), a plurality of valves (V1 , .... Vn) located on the fluid circuit (2) and configurable to define different fluid paths for the fluid inside the fluid circuit (2), at least one sensor (18; 31; 54) configured to measure a property of the fluid flowing in the main fluid line (3), wherein the at least one sensor (18; 31; 54) is located downstream the first injection point (j1), the second injection point (j2) and the mixing chamber (17), a control unit (19) configured to operate the plurality of valves to define the different fluid paths inside the fluid circuit (2), wherein the control unit (19) is configured to execute a medical fluid preparation procedure comprising a first concentrate mixing sequence and a second concentrate mixing sequence, wherein, during execution of the first concentrate mixing sequence, the control unit (19) is configured to:• operate the main pump (6) to pump fluid in the main fluid line (3);• operate the first dosing pump (11) to inject first concentrate from the first concentrate container (9) into the main fluid line (3) at the first injection point (j 1 );• receive signals from the at least one sensor (18; 31; 54) relating to the property of the mixture of water and first concentrate in the main fluid line (3);• control a first dosing pump flow rate and / or a main pump flow rate or a ratio thereof based on the received signals relating to the property of the mixture of water and first concentrate in the main fluid line (3); wherein, during execution of the second concentrate mixing sequence, the control unit (19) is further configured to:• operate the second dosing pump (16) to inject second concentrate from the second concentrate container (14) into the main fluid line (3) at the second injection point (j2);• receive signals from the at least one sensor (18; 31 ; 54) relating to the property of the mixture of water, first concentrate, and second concentrate in the main fluid line (3);• control a second dosing pump flow rate and / or a ratio between the second dosing pump flow rate and the main pump flow rate and / or a ratio between the second dosing pump flow rate and the first dosing pump flow rate based on the received signals relating to the property of the mixture of water, first concentrate, and second concentrate in the main fluid line (3).

2. Apparatus according to claim 1, wherein the control unit (19) is configured to operate the second dosing pump (16) subsequent to execution of the first concentrate mixing sequence.

3. Apparatus according to any one of the previous claims, wherein said property of the fluid is chosen in the group consisting of a conductivity of the fluid, a concentration of a substance in the fluid, a concentration dependent physical property, such as sound velocity, viscosity, density, a temperature of the fluid, an optical property of the fluid, combinations thereof.

4. Apparatus according to any one of the previous claims, wherein the at least one sensor (18; 31 ; 54) comprises at least one of a conductivity sensor, a concentration sensor, a temperature sensor, an optical sensor, a viscosity sensor, a density sensor, and a sound sensor.

5. Apparatus according to any one of the previous claims, wherein, during execution of the first concentrate mixing sequence, the control unit (19) is configured to:• obtain a first property-of-the-fluid target for a mixture of water and first concentrate; wherein controlling the first dosing pump flow rate and / or the main pump flow rate or the ratio thereof comprises:• control a first dosing pump flow rate and / or a main pump flow rate to bring the property of the mixture of water and first concentrate in the main fluid line (3) towards the first property-of-the-fluid target;• measure the property of the mixture of water and first concentrate in the main fluid line (3);• determine the first dosing pump flow rate and the main pump flow rate or a ratio thereof when the measured property fulfills a first criteria of having reached the first property-of-the-fl uid target.

6. Apparatus according to claim 5, wherein, after determining the first dosing pump flow rate and the main pump flow rate or the ratio thereof, the control unit (19) is further configured to:• operate the first dosing pump flow rate and the main pump flow rate at the determined first dosing pump flow rate and main pump flow rate or at the determined ratio to allow the property of the mixture of water and first concentrate to stabilize;• calculate a statistical property, e.g., a filtered mean, of said property of the mixture of water and first concentrate;• store the statistical property as a reached first property for the mixture of water and first concentrate.

7. Apparatus according to anyone of claims 5 and 6, wherein said first criteria comprises verifying that the mixture of water and first concentrate is within a predefined range of the first property-of-the-fluid target, such as within 2%, in particular within 0.5% and for example within 0.2%.

8. Apparatus according to anyone of claims 5 to 7, wherein the control unit (19) is configured to: calculate the first property-of-the-fluid target for a mixture of water and first concentrate based on nominal concentrations of one or more solutes in the first concentrate (F) and on conductivity equations for each of said solutes in the first concentrate (F); or receive the first property-of-the-fluid target as external input; or receive the first property-of-the-fluid target as stored data optionally after experimentally determining it.

9. Apparatus according to any one of the previous claims, wherein, during execution of the first concentrate mixing sequence, the control unit (19) is configured to: keep inactive the second dosing pump (16) with no flow rate in the second dosing line (15).

10. Apparatus according to any one of the previous claims, wherein, during execution of the first concentrate mixing sequence, the control unit (19) is configured to: control the first dosing pump flow rate particularly based on a property feedback controller, and keep the main pump flow rate substantially constant.11 . Apparatus according to any one of the previous claims, wherein, during execution of the second concentrate mixing sequence, the control unit (19) is configured to: obtain a second property-of-the-fluid target for a mixture of water, first concentrate, and second concentrate;wherein controlling second dosing pump flow rate and / or a ratio between the second dosing pump flow rate and the main pump flow rate and / or a ratio between the second dosing pump flow rate and the first dosing pump flow rate comprises:• change the second dosing pump flow rate and / or the main pump flow rate, keeping constant the ratio of the first dosing pump flow rate and the main pump flow rate, to bring the property of the mixture of water, first concentrate, and second concentrate in the main fluid line (3) towards the second property- of-the-fluid target;• measure the property of the mixture of water, first concentrate, and second concentrate in the main fluid line (3);• determine the second dosing pump flow rate or a ratio between the second dosing pump flow rate and the main pump flow rate or a ratio between the second dosing pump flow rate and first dosing pump flow rate when the measured property fulfills a second criteria of having reached the second conductivity target.

12. Apparatus according to claim 11 , wherein the control unit (19) is configured to: calculate the second property-of-the-fluid target for the mixture of water, first concentrate, and second concentrate based on a target concentration for the mixture of water, first concentrate, and second concentrate of at least one substance in the second concentrate (S), in particular said substance being glucose; or receive the second property-of-the-fluid target as external input or as stored data optionally after experimentally determining the second property-of-the-fluid target.

13. Apparatus according to claim 12, wherein the control unit (19) is configured to: calculate the second property-of-the-fluid target further based on a reached first property, being the first property-of-the-fluid target plus a control error, in particular wherein the control error is a difference between the first property-of-the-fluid target and the reached first property achieved when controlling the first dosing pump (11) and the main pump (6) at the determined first dosing pump flow rate and main pump flow rate or the ratio thereof.

14. Apparatus according to any one of the previous claims 11 to 13, wherein the second property-of-the-fluid target for a mixture of water, first concentrate, and second concentrate is lower than the first property-of-the-fluid target for a mixture of water and first concentrate.

15. Apparatus according to any one of the previous claims, wherein, during execution of the second concentrate mixing sequence, the control unit (19) is configured to: control the second dosing pump (16) at an overdose flow rate to inject an overdose of the second concentrate (S) into the main fluid line (3); and subsequentlymeasure the property of the mixture of water, first concentrate, and second concentrate in the main fluid line (3); reduce the overdose flow rate of the second dosing pump (16) based on the subsequently measured property of the mixture of water, first concentrate, and second concentrate.

16. Apparatus according to claim 15, wherein the control unit (19) is configured to: reduce the overdose flow rate of the second dosing pump (16) further based on a delta between the first property-of-the-fluid target and the second property-of-the-fluid target.

17. Apparatus according to claim 16, wherein the control unit (19) is configured to calculate a speed of the second dosing pump (16) based on the following formula:Target S response Locked S pump speed = Overdose S pump speed ■ - - -Overdose S response wherein:• 'Locked S pump speed’ is the calculated speed of the second dosing pump (16);• 'Overdose S pump speed’ is a set speed of the second dosing pump (16) to generate the overdose flow rate;• 'Target S response’ is the delta between the reached first property-of-the-fluid and the second property- of-the-fluid target;• 'Overdose response’ is an actual delta between the reached first property-of-the-fluid and a measured property of the mixture of water, first concentrate, and second concentrate after the generation of the overdose flow rate.

18. Apparatus according to any one of the previous claims 1 to 13, wherein, during execution of the second concentrate mixing sequence, the control unit (19) is configured to: control the second dosing pump flow rate particularly based on a property feedback controller, and keep the main pump flow rate and the first dosing pump flow rate, and / or a ratio thereof, substantially constant.

19. Apparatus according to any one of the previous claims 1 to 18, wherein the control unit (19) is configured to control the plurality of valves to define a first mixing flow path comprising:• an initial portion (48) of the main fluid line (3) including the first injection point (j1), the second injection point (j2) and the mixing chamber (17) and a diverting point (47); and• an evacuation line (40) fluidly connected to the diverting point (47) and routing the fluid towards a drain (27),wherein the first mixing flow path is defined at least during execution of the first concentrate mixing sequence and / or the second concentrate mixing sequence and the at least one sensor (18; 31; 54) comprises: optionally a first sensor (18) located in the initial portion (48) of the main fluid line (3) upstream of the diverting point (47); a second sensor (31) located on the evacuation line (40) to measure the property of the fluid flowing in the initial portion of the main fluid line (3).

20. Apparatus according to claim 19, wherein, the main fluid line (3) further comprises a terminal portion (49) extending from the diverting point (47) to the outlet point (5), when the first mixing flow path is defined, a diverting valve (V13) of the plurality of valves is configured to allow the fluid to flow from the initial portion (48) of the main fluid line (3) to the evacuation line (40), during execution of the first concentrate mixing sequence no fluid is flowing in the terminal portion (49).

21. Apparatus according to any one of the previous claims 19 to 20, wherein the plurality of valves controlled by the control unit (19) to define the first mixing flow path comprises one or more of: a water inlet valve (V3) located on the initial portion (48) of the main fluid line (3), set in a configuration that allows water to flow along the initial portion (48); a recirculation valve (V15) located on the initial portion (48) of the main fluid line (3), set in a configuration that allows water to flow along the initial portion (48); a discharge valve (V6) downstream the mixing chamber (17) located on the initial portion (48) of the main fluid line (3), set in a configuration that allows water to flow along the initial portion (48); a diverting valve (V13) located on the initial portion (48) of the main fluid line (3), set in a configuration that allows the fluid to flow from the initial portion (48) of the main fluid line (3) to the evacuation line (40), the diverting valve (V13) being set in a configuration that prevents the fluid to flow from the initial portion (48) to a terminal portion (49) of the main fluid line (3); and a closure valve (V12) located on the evacuation line (40), set in a configuration that allows the fluid to flow through the evacuation line (40) towards a drain (27).

22. Apparatus according to any one of the previous claims 1 to 21 , wherein the control unit (19) is configured to control the plurality of valves to define a medical fluid delivery flow path comprising the main fluid path (3) from the inlet point (4) to the outlet point (5), during a medical fluid delivery phase, pure water flowing through the inlet point and towards the first injection point (j 1 ), and a medical fluid, for example a dialysis treatment fluid, flowing out of the outlet point (5).

23. Apparatus according to any one of the previous claims 1 to 22, wherein further comprising a secondary mixing chamber (20) placed on the main fluid line (3) and located downstream of the first injection point (j1) and the second injection point (j2) and upstream of the mixing chamber (17).

24. Apparatus according to any one of the previous claims 1 to 23, wherein the apparatus further comprises: a first concentrate container (9) containing a first concentrate (F), with a port (8) fluidly connected to the first concentrate access (7), in particular the first concentrate (F) being in liquid form; and / or a second concentrate container (14) containing a second concentrate (S), with a port (13) fluidly connected to the second concentrate access (12), in particular the second concentrate (S) being in liquid form, in particular the second concentrate (S) comprising an osmotic agent, such as glucose.

25. Apparatus according to any one of the previous claims 1 to 24, wherein the apparatus is for the online preparation of peritoneal dialysis (PD) fluid from water and concentrates, in particular upon request from a PD cycler, and is configured to prepare the medical fluid and simultaneously deliver the medical fluid to the outlet point (5), e.g., in order to be used immediately and / or in real time by the external device or to be stored in an external container.

26. Apparatus according to any one of the previous claims 1 to 25, wherein the main pump (6) is located upstream of the at least one sensor (18; 31 ; 54) along a fluid flow direction.

27. Apparatus according to any one of the previous claims 1 to 26, wherein the main pump (6) is located downstream the first injection point (j1), the second injection point (j2) and upstream or downstream of the mixing chamber (17).

28. A medical fluid generation apparatus (1) comprising: a fluid circuit (2) including a main fluid line (3) developing between an inlet point (4) for receiving water and an outlet point (5) connectable to a treatment medical device, a main pump (6) located on the main fluid line (3) to pump fluid at least in the main fluid line (3), wherein the fluid circuit (2) further includes: o a first concentrate access (7) fluidly connectable to a port (8) of a first concentrate container (9) containing a first concentrate (F), o a first dosing line (10) putting in fluid communication the first concentrate access (7) and the main fluid line (3) at a first injection point (j 1) located between the inlet point (4) and the outlet point (5), o a second concentrate access (12) fluidly connectable to a port (13) of a second concentrate container (14) containing a second concentrate (S), o a second dosing line (15) putting in fluid communication the second concentrate access (12) and the main fluid line (3) at a second injection point (j2) located between the inlet point (4) and the outlet point (5); o a mixing chamber (17) placed on the main fluid line (3) and located downstream the first injection point (j1) and the second injection point (j2) and upstream the outlet point (5), the mixing chamber (17) comprising a mixing chamber inlet (17a) configured to receive fluid fromthe main fluid line (3) and a mixing chamber outlet (17b) configured to release fluid to the main fluid line (3), a first dosing pump (11) configured to pump fluid in the first dosing line (10), a second dosing pump (16) configured to pump fluid in the second dosing line (15), a plurality of valves (V1 , .... Vn) located on the fluid circuit (2) and configurable to define different fluid paths for the fluid inside the fluid circuit (2), at least one sensor (18; 31; 54) configured to measure a property of the fluid flowing in the main fluid line (3), wherein the at least one sensor (18; 31; 54) is located downstream the first injection point (j1), the second injection point (j2) and the mixing chamber (17), a control unit (19) configured to operate the plurality of valves to define the different fluid paths inside the fluid circuit (2), wherein the control unit (19) is configured to execute a medical fluid preparation procedure comprising a first concentrate mixing sequence and a second concentrate mixing sequence, wherein, during execution of the first concentrate mixing sequence, the control unit (19) is configured to:• obtain a first property-of-the-fluid target for a mixture of water and first concentrate;• operate the main pump (6) to pump fluid in the main fluid line (3);• operate the first dosing pump (11) to inject first concentrate from the first concentrate container (9) into the main fluid line (3) at the first injection point (j 1 );• receive signals from the at least one sensor (18; 31 ; 54) relating to the property of the mixture of water and first concentrate in the main fluid line (3);• control a first dosing pump flow rate and / or a main pump flow rate or a ratio thereof based on the received signals relating to the property of the mixture of water and first concentrate in the main fluid line (3); wherein, during execution of the second concentrate mixing sequence, the control unit (19) is further configured to:• obtain a second property-of-the-fluid target for a mixture of water, first concentrate, and second concentrate by calculating the second property-of-the-fluid target based on a target concentration for the mixture of water, first concentrate, and second concentrate of at least one substance in the second concentrate (S), for example glucose, and based on a reached first property, being the first property- of-the-fluid target plus a control error, in particular wherein the control error is a difference between the first property-of-the-fluid target and the reached first property achieved when controlling the first dosing pump (11) and the main pump (6) at the determined first dosing pump flow rate and main pump flow rate or the ratio thereof;• operate the second dosing pump (16) to inject second concentrate from the second concentrate container (14) into the main fluid line (3) at the second injection point (j2);• receive signals from the at least one sensor (18; 31 ; 54) relating to the property of the mixture of water, first concentrate, and second concentrate in the main fluid line (3); control a second dosing pump flow rate and / or a ratio between the second dosing pump flow rate and the main pump flow rate and / or a ratio between the second dosing pump flow rate and the first dosing pump flow rate based on the received signals relating to the property of the mixture of water, first concentrate, and second concentrate in the main fluid line (3), wherein the control unit (19) is further configured to: o calculate the second property-of-the-fluid target for the mixture of water, first concentrate, and second concentrate based on a target concentration for the mixture of water, first concentrate, and second concentrate of at least one substance in the second concentrate (S), in particular said substance being glucose; or o receive the second property-of-the-fluid target as external input or as stored data.

29. A method (1000) of generating a medical fluid comprising: providing (1001) a medical fluid generation apparatus (1) comprising: o a fluid circuit (2) for receiving water; o a main pump (6) located on the fluid circuit (2), o a plurality of valves (V1, .... Vn) located on the fluid circuit (2) and configurable to define different fluid paths for the fluid inside the fluid circuit (2), o at least one sensor (18; 31 ; 54) configured to measure a property of the fluid flowing in the fluid circuit (2), o a control unit (19) configured to operate the plurality of valves to define the different fluid paths inside the fluid circuit (2), executing (1002) a medical fluid preparation procedure comprising a first concentrate mixing sequence (1003) and a second concentrate mixing sequence (1004), wherein, during execution of the first concentrate mixing sequence (1003), the method comprises:• operating (1005) a main pump (6) to pump fluid in a main fluid line (3) of the fluid circuit (2);• operating (1006) a first dosing pump (11) to inject a first concentrate from a first concentrate container (9) into the main fluid line (3) at a first injection point (j1) where the first concentrate mixes with water;• obtaining (1007) signals from the at least one sensor (18; 31; 54) relating to the property of the mixture of water and first concentrate in the main fluid line (3);• controlling (1008) a first dosing pump flow rate and / or a main pump flow rate or a ratio thereof based on the received signals relating to the property of the mixture of water and first concentrate in the main fluid line (3); wherein, during execution of the second concentrate mixing sequence (1004), the method further comprises:• operating (1011) a second dosing pump (16) to inject a second concentrate from a second concentrate container (14) into the main fluid line (3) at a second injection point (j2) where the second concentrate mixes with the first concentrate and water;• obtaining (1012) signals from the at least one sensor (18; 31; 54) relating to the property of the mixture of water, first concentrate, and second concentrate in the main fluid line (3);• controlling (1013) a second dosing pump flow rate based on the received signals relating to the property of the mixture of water, first concentrate, and second concentrate in the main fluid line (3).

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