Medical fluid generation apparatus

Abstract

A medical tubing set (63) for peritoneal dialysis treatment comprising a supply line (64) having one end (64a) for connection to a medical fluid generation apparatus (1); a container (65) with a port (65a); a container line (66) having one end (66a) connected or configured to be connected to the port (65a) of the container (65); a cassette (68) comprising a first inlet port (HB), a patient line port (PL) and a drain line port (DL), a cassette line (67) having one end (67a) connected or configured to be connected to the first inlet port (HB) of the cassette (68), a patient line (73) connected to the patient line port (PL); a drain line (74) connected to the drain line port (DL); a second end (64b) of the supply line (64), a second end (66b) of the container line (66) and a second end (67b) of the cassette line (67) are in fluid communication with each other, in particular at a tube fitting (69).

Description

TITLEMEDICAL FLUID GENERATION APPARATUSBACKGROUND

[0001] The present disclosure relates generally to a medical fluid generating apparatus for pressure controlled replenishment of medical fluid of an external device. In particular, the medical fluid generated is dialysis fluid to be used for dialysis treatments. More particularly, embodiments of the present disclosure relate to on-line generation of medical fluid, which is supplied to an external container or bag which is a reservoir of medical fluid for use by a treatment apparatus (e.g. a peritoneal dialysis apparatus or a haemodialysis apparatus). In a specific aspect, the present disclosure relates to the on-line preparation of PD (peritoneal dialysis) fluid for delivery to, for example, 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. 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, and restore essential substances in, a patient's blood. In HD dialysis fluid is flowing on one side of a semi-permeable membrane. On the other side the patient's blood is flowing. By this setup a diffusive gradient occurs along the semi-permeable between the two fluids. HD fluids are typically created by the dialysis machines by mixing concentrates and clean water.

[0005] Hemofiltration ("HF”) is an alternative renal replacement therapy HF is accomplished by pulling more plasma water from the patient than what is needed to restore the fluid balance. By that the principle of convection is used to remove toxins. Restore the fluid balance in the patient by adding what's called substitution or replacement fluid to the extracorporeal circuit during treatment. HF treatment is particularly beneficial in removing middle and large molecules..

[0006] Hemodiafiltration (“HDF”) is a treatment modality that combines convective and diffusive transport mechanism principles.

[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 water pass from the patient's bloodstream, through the capillaries in the peritoneal membrane, and into the dialysis fluid due to diffusion and osmosis, i.e., an osmotic gradient occurs across the membrane. An osmotic agentin 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 empty fresh dialysis fluid bag from the catheter and allows the dialysis fluid to dwell within the peritoneal cavity, wherein the transfer of waste, toxins, and excess water takes place. After a dwell period, the patient repeats the manual dialysis procedure, for example, four times per day. If the peritoneal cavity is not initially full of used dialysis fluid, the sequence is instead fill, dwell, and drain. Manual peritoneal dialysis requires a significant amount of time and effort from the patient, leaving ample room for improvement.

[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 peritoneal cavity 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 be of different type such that the fluid can dwell longer in the peritoneal cavity. The last fill is drained / replaced during the day using the CAPD technique.

[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 / 6 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.

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

[0012] 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.

[0013] During use, the dialysis fluid generation device is connected by tubing to a PD cycler. This cycler is responsible for managing the infusion and drainage of dialysis fluid into and out of the patient's peritoneum. The dialysis fluid generation device continuously prepares the dialysis fluid and pumps it to the cycler as required during the treatment session. This process can be driven by a pump in the dialysis fluid generation device, which ensures a steady and controlled flow of dialysis fluid into the cycler. Electronic communication between the two devices allows correct and synchronized operation of both the dialysis fluid generation device, which prepares the correct amount of fluid at the correct time, and the PD cycler, which receives the dialysis fluid at the correct time.

[0014] In order to work as described above, both the dialysis fluid preparation device and the PD cycler must be configured to work together. In this respect, it is not possible to connect a generic dialysis fluid generation device to a generic PD cycler due to the lack of communication and coherent protocols. The lack of electronic communication between the dialysis fluid generator and the PD cycler can lead to several operational problems. Without electronic communication, it can be difficult to coordinate the flow rate of dialysis fluid between the machine and the cycler. If the dialysis fluid generator produces fluid either too quickly or too slowly compared to the cycler's needs, this can result in inefficient treatment or increased risk of infection due to fluid stagnation or overflow. The timing of fluid delivery may not be synchronized with the patient's treatment schedule, potentially leading to interruptions or excessive fluid build-up.

[0015] Operators may need to manually monitor and adjust the machine and cycler, increasing workload and the potential for human error.

[0016] In summary, electronic communication between a dialysis fluid generation device and a PD cycler is usually relevant for efficient, safe and synchronized operation. It ensures that treatment is delivered effectively, taking into account the specific medical needs and safety of the patient, while reducing the burden on healthcare providers and nurses.

[0017] There may be therefore a need to enable a dialysis fluid generation device to be fluidly connected to a PD cycler or other external medical device that requires medical fluid, in the event that the external medical device does not communicate electronically with the dialysis fluid generation device.

[0018] US2022 / 0409792 outlines a comprehensive dialysis system equipped with a flow regulation device, specifically designed to address the fluid delivery challenges associated with both home and institutional dialysis treatments. The primary focus of this system is to regulate the fluid flow to the dialysis device, accommodating the variable fluid demands typical in dialysis procedures. The system's cornerstone is the flow regulation device, which dynamically adjusts its internal volume to match the fluiddemand cycles of the dialysis machine. When the machine's fluid demand decreases, the device expands to store excess fluid, and it contracts to release fluid when the demand increases. This operation manages the pressures within the system and ensures a steady, regulated flow to the dialysis device. By modulating the fluid supply in this way, the system avoids the inefficiencies and potential complications of supplying fluid at a constant, high rate, which could lead to significant waste and operational challenges.

[0019] In an alternative solution, a pressure control for fluid delivery is designed to manage the variable demands of the dialysis machine through a dynamic flow regulation device. Pressure sensors integrated into the system monitor these changes to provide real-time feedback to a controller, which adjusts the flow rates accordingly. This pressure-based feedback mechanism ensures the dialysis machine receives a steady supply of dialysate or purified water, matching its moment-to-moment needs. The system uses a fluid connection to communicate information from the dialysis machine to the fluid source. When the dialysis machine draws fluid at a high rate, the fluid source experiences a pressure drop on an outlet line and more fluid is pumped. When the dialysis machine reduces the extraction rate, the pressure on the outlet line of the fluid source increases, which can be detected by the pressure transducer, resulting in a reduced flow rate to the dialysis machine.

[0020] Document US11207454 discloses systems for preparing peritoneal dialysis fluid and administering a peritoneal dialysis treatment. Peritoneal dialysis fluid is prepared at a point of use automatically using a daily sterile disposable fluid circuit and one or more long-term concentrate containers that are changed only after multiple days (e.g. weekly). The daily disposable may have concentrate containers that are initially empty and are filled from the long-term concentrate containers once per day at the beginning of a treatment. In one specific embodiment, once the device is connected to a cycler an active pressure communication protocol is used. The active pressure communication system allows the dialysis device and the water source controller to coordinate without direct electronic connections. This method utilizes pressure pulse signals generated by modulating the operation of a pump within the dialysis device. These signals, which might involve changes in pump speed, direction, or intermittent operation, are transmitted through the water line to the water source. A pressure sensor at the water source detects these pulses. A decoder then interprets the variations in pressure as specific operational commands, such as starting or stopping the pump, or adjusting flow rates. This setup allows the two units to synchronize their operations dynamically, ensuring the dialysis fluid is prepared with the correct water flow and volume as required by the treatment protocol. This pressure-based communication system does require precise calibration and maintenance to ensure reliable signal detection and interpretation, and its mechanical complexity might impact long-term reliability.SUMMARY

[0021] The present disclosure sets forth apparatus and methods for supplying a medical fluid, particularly a dialysis fluid, such as peritoneal dialysis (“PD”) fluid and hemodialysis ("HD”) fluids to anexternal medical device. While the present disclosure focuses more on PD fluid, the teachings discussed herein may also be 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.

[0022] The medical fluid generation apparatus is fluidly connected to the external medical device and is capable of providing the right amount of medical fluid at the right time without an electric or electronic communication being in place between the apparatus and the external device. Moreover, the apparatus can be properly connected to many standard external devices, particularly PD cyclers.

[0023] 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) having an inlet point (4) for receiving water and an outlet point (5) for delivering of a medical fluid to an external medical device (101), a main pump (6) located on the fluid circuit (2) to cause a flow of the medical fluid; a pressure sensor (P2) for sensing the pressure in the fluid circuit (2); a control unit (19) configured to operate the main pump (6) and in communication with the pressure sensor (P2) to receive an outlet pressure signal from the pressure sensor (P2) indicative of a pressure of the medical fluid downstream of the pressure sensor (P2), in particular at the outlet point (5) of the fluid circuit (2) and downstream of it in a supply line connected to the outlet point (5), wherein optionally the control unit (19) is configured to: i. determine a no-flow pressure based on the outlet pressure signal in a no-flow condition in which there is no medical fluid supply from the medical fluid generating apparatus (1) to the external medical device (101); ii. detect a pressure variation from the no-flow pressure based on the outlet pressure signal in a medical fluid usage condition in which there is both no medical fluid supply from the medical fluid generating apparatus (1) to the external medical device (101) and medical fluid flow in the external medical device (101);iii. determine a state of need for the medical fluid from the external medical device (101) based on the outlet pressure signal, wherein the state of need is determined based on a switch from the medical fluid usage condition to the no-flow condition; iv. in particular either command a supply of the medical fluid to the external medical device (101) when or after the state of need is detected, or verify that a supply of the medical fluid to the external medical device (101) is occurring when or after the state of need is detected.

[0024] In the no flow condition of the apparatus, the no-flow pressure sensed is the head height between a supply line (66), e.g., at a split point, namely a tube fitting (69), and the pressure sensor (P2) in condition of no medical fluid flow from the apparatus (1). When the no-flow pressure is determined, the medical fluid generating apparatus (1) is in a fluid production pause mode (or non-production mode) and the external medical device (101) is not using the medical fluid which is contained in a container (65) of a medical tubing set (63) connected to the outlet point (5) of the apparatus (1).

[0025] In the medical fluid usage condition of the apparatus (1), the medical fluid generating apparatus (1) is still in the fluid production pause mode and the external medical device (101) is changed to a phase using the medical fluid; in particular the medical tubing set (63) remains connected to the outlet point (5) of the apparatus (1) and there is a medical fluid flowing from the container (65) to a cassette (68) of the same medical tubing set (63). See also figure 4A.

[0026] The state of need for the medical fluid is determined when the medical fluid flow from the container (65) to the cassette (68) of the medical tubing set (63) is interrupted, meaning that a certain amount of the medical fluid (for example all the medical fluid) has been removed from the container (65) and used. The apparatus is still in the fluid production pause mode.

[0027] The supply of medical fluid is only commanded either as soon as the state of need is determined or sometimes after the state of need is determined.

[0028] In a further independent aspect, a method of supplying a medical fluid from a medical fluid generating apparatus (1) to an external medical device (101), wherein the medical fluid generating apparatus (1) comprises: a fluid circuit (2) having an inlet point (4) for receiving water and an outlet point (5) for delivering of a medical fluid to an external medical device (101), a main pump (6) located on the fluid circuit (2) to cause a flow of the medical fluid; one or more pressure sensors for sensing the pressure in the fluid circuit (2); wherein the method comprises the following steps executed by a control unit (19):I. determining a no-flow pressure based on an outlet pressure of the medical fluid at the outlet point (5) of the fluid circuit (2) in a no-flow condition in which there is no medical fluid supply from the medical fluid generating apparatus (1) to the external medical device (101);II. detecting a pressure variation from the no-flow pressure based on the outlet pressure signal in a medical fluid usage condition in which there is both no medical fluid supply from the medical fluidgenerating apparatus (1) to the external medical device (101) and medical fluid flow in the external medical device (101); ill. determining a state of need for the medical fluid from the external medical device (101) based on the outlet pressure signal, wherein the state of need is determined based on a switch from the medical fluid usage condition to the no-flow condition; iv. in particular either commanding a supply of the medical fluid to the external medical device (101) when or after the state of need is detected or verify that a supply of the medical fluid to the external medical device (101) is occurring when or after the state of need is detected.

[0029] In the above method 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.

[0030] In a further independent aspect, a medical fluid generating apparatus (1) is provided comprising: a fluid circuit (2) having an inlet point (4) for receiving water and an outlet point (5) for delivering of a medical fluid to an external medical device (101), a main pump (6) located on the fluid circuit (2) to cause a flow of the medical fluid; a pressure sensor (P2) for sensing a pressure in the fluid circuit (2); a communication line (94) to receive data from an external medical device (101); a control unit (19) configured to operate the main pump (6) and in communication with the communication line (94) the pressure sensor (P2) to receive an outlet pressure signal from the pressure sensor (P2) indicative of a pressure of the medical fluid downstream of the pressure sensor (P2); wherein the control unit (19) is configured to receive data from the external medical device (101) via the communication line (94), the data comprising:• need-state data indicating a requirement for the medical fluid from the external medical device (101); and• no-need-state data indicating the absence of a requirement for the medical fluid from the external medical device (101); and wherein the control unit (19) is further configured to control the supply of the medical fluid to the external medical device (101) by:• initiating or maintaining the supply of the medical fluid when or after the need-state data is received; and• preventing or interrupting the supply of the medical fluid when or after the no-need-state data is received, the control unit (19) being configured to:i. determine a no-flow pressure based on the outlet pressure signal in a no-flow condition in which there is no medical fluid supply from the medical fluid generating apparatus (1) to the external medical device (101);II. detect a pressure variation from the no-flow pressure based on the outlet pressure signal in a medical fluid usage condition in which there is both no medical fluid supply from the medical fluid generating apparatus (1) to the external medical device (101) and medical fluid flow in the external medical device (101); ill. determine a state of need for the medical fluid from the external medical device (101) based on the outlet pressure signal, wherein the state of need is determined based on a switch from the medical fluid usage condition to the no-flow condition, iv. optionally verify that a supply of the medical fluid to the external medical device (101) is occurring when or after the state of need is detected and / or command a supply of the medical fluid to the external medical device (101) when or after the state of need is detected.

[0031] With the configuration including the communication line (94), the medical fluid generating apparatus (1) is capable of direct communication with the external medical device (101) and is therefore continuously updated regarding the actual need for medical fluid, which can be produced on demand. The medical fluid generating apparatus (1) further includes an algorithm configured to monitor and verify the correctness of the data exchange with the external medical device (101). This algorithm determines the status of the fluid need based on the measured pressure and can be used to confirm the reliability of the received data from the external medical device (101).

[0032] In a depending aspect according to the previous independent aspect, the communication line (94) is a wired communication line (e.g., an ethernet USB, or serial connection) or a wireless connection line (e.g., Wi-Fi, Bluetooth, Zigbee, or proprietary radio-frequency (RF) connection).

[0033] In a further depending aspect according to the previous any one of the previous two aspects, in case the no-need-state data is received by the control unit (19) and the state of need for the medical fluid is determined based on the outlet pressure signal, an alert is provided to the user.

[0034] In a 2ndaspect according to any one of the previous aspects, the control unit (19) is configured to interrupt the supply of the medical fluid after a predetermined amount of medical fluid has been supplied to the external medical device (101).

[0035] In a 2ndbis aspect according to any one of the previous aspects, the control unit (19) is configured to interrupt the supply of the medical fluid based on a condition on the outlet pressure signal.

[0036] In a 3rdaspect according to aspect 2 bis, the control unit (19) is configured interrupt the supply of the medical fluid when the outlet pressure signal is above an upper threshold. In other terms a condition of non-need for the medical fluid is determined based on the outlet pressure signal, namely when the pressure signal is above the threshold.

[0037] In a 4thaspect according to any one of the previous aspects, the control unit (19) is configured to:• receive an activation signal commanding a first medical fluid supply to the external medical device (101), in particular the first medical fluid supply being a supply of a predetermined medical fluid volume,• determine a no-flow pressure based on the outlet pressure signal after the first medical fluid supply is completed.

[0038] In a 5thaspect according to any one of the previous aspects, the fluid circuit (2) comprises a main fluid line (3) with delivery tract (30) leading the medical fluid to the outlet point (5), a delivery valve (V8) and the pressure sensor (P2) being located on the delivery tract (30), in particular the delivery valve (V8) being located between the pressure sensor (P2) and the outlet point (5).

[0039] In a 6thaspect according to the previous aspects 4 and 5, when the first medical fluid supply is completed, the control unit (19) is configured to: first place the apparatus in a fluid production pause mode which stops a delivery of medical fluid to the external medical device (101), the delivery valve (V8) remaining open in the fluid production pause mode, allowing a pressure downstream of the pressure sensor (P2), in particular downstream of the outlet point (5) in a supply line connected to the outlet point (5), to be sensed by the pressure sensor (P2); and then determine the no-flow pressure.

[0040] In a 7thaspect according to any one of the previous aspects, the control unit (19) is configured to monitor the pressure variation from the no-flow pressure over time and to determine based on the monitored pressure variation over time an amount of medical fluid required when the state of need is determined.

[0041] In an 8thaspect, according to the previous aspect, the pressure variation from the noflow pressure is a pressure drop lowering the pressure signal to values below the no-flow pressure.

[0042] In a 9thaspect according to any one of the previous two aspects, the control unit (19) is configured to retrieve or determine a stroke volume and / or a fluid flow rate of a pumping action exerted by one or more pump chambers (72, 73) of the cassette (68) by a pumping mechanism (90) of the external medical device (101) and, based on the monitored pressure variation over time, calculate the amount of medical fluid required when the state of need is determined.

[0043] In an 10thaspect according to any one of the previous three aspects, the monitored pressure variation over time defines a plurality of pressure oscillations, each corresponding to a pump stroke, the control unit (19) knowing the stroke volume of a pumping action exerted by the one or more pump chambers (72, 73) of the cassette (68) by the pumping mechanism (90) of the external medical device (101) being configured to calculate a total delivered medical fluid volume and consequently the amount of medicalfluid required when the state of need is determined, in particular the total delivered medical fluid volume is obtained by multiplying the number of the plurality of pressure oscillations by the stroke volume.

[0044] In an 11thaspect according to any one of the previous aspects, the control unit (19) is configured to execute the steps (II), (ill) and (iv) in temporal sequence.

[0045] In a 12thaspect according to any one of the previous aspects, the control unit (19) is configured to repeat cyclically and in sequence the steps of (I) detecting a pressure variation from the noflow pressure, (II) determining a state of need for the medical fluid from the external medical device (101 ) and (ill) command a supply of the medical fluid.

[0046] In a 13thaspect according to any one of the previous aspects, the control unit (19) is configured to monitor the pressure of the medical fluid at the outlet point (5) through the pressure sensor (P2) during step (iv) when the supply of the medical fluid occurs, more in detail the control unit (19) verifying that an absolute value of the pressure signal in the medical fluid is higher than the no-flow pressure.

[0047] In a 14thaccording to any one of the previous aspects, the medical fluid generation apparatus (1) comprises: the fluid circuit (2) including a main fluid line (3) developing between the inlet point (4) for receiving water and the outlet point (5), the 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 (]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 (]1) 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 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), the control unit (19) configured to operate the plurality of valves to define the different fluid paths inside the fluid circuit (2).

[0048] 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, ..., Vr’ is used.

[0049] In a 15thaspect according to the previous aspect, 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.

[0050] 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.

[0051] In a 16thaspect according to any one of the previous two aspects, the at least one sensor (18; 31 ; 54) comprises a first sensor (18) placed on the main fluid line (3), in particular 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).

[0052] In a 17thaspect according to any one of the previous three aspects, 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).

[0053] In an 18thaspect according to any one of the previous four aspects, the main pump (6) is located upstream of the at least one sensor (18; 31 ; 54) along a fluid flow direction and more specifically downstream of the first injection point (j 1 ), the second injection point (j2) and the mixing chamber (17).

[0054] In a 19thaspect according to any one of the previous five 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), optionally 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).

[0055] In a 20thaspect according to any one of the previous six aspects, the plurality of valves comprises a water inlet valve (V3) placed on the main fluid line (3) upstream the first junction point (j1) and the second junction point (j2), and optionally a pressure regulator (41) placed on the main fluid line (3) upstream the first junction point (j1) and the second junction point (j2), optionally downstream a water inlet valve (V3).

[0056] In a 21staspect according to any one of the previous seven aspects, the apparatus further comprises a first pressure sensor (P1) located on the main fluid line (3) between the first injection point (]1) and the second injection point (j2).

[0057] In a 22ndaspect according to any one of the previous eight 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).

[0058] In a 23rdaspect according to any one of the previous nine 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.

[0059] The filter (24) aims at reducing any microbial contamination before fluid delivery to a receiving device or means, such as e.g., an external dialysis unit or a set of bags.

[0060] In a 24thaspect 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.

[0061] In a 25thaspect 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).

[0062] 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).

[0063] In a 26thaspect 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.

[0064] In a 27thaspect according to any one of the previous four 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.

[0065] The second filter (26) aims at further reducing any microbial contamination before fluid delivery to the external dialysis unit (23).

[0066] In a 28thaspect 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.

[0067] In a 29thaspect 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).

[0068] The second filter (26) is flushed to drain (27) using the valve (V11) and the second flushing line (28).

[0069] In a 30thaspect 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.

[0070] In a 31staspect 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).

[0071] The common line tract (25a) is directly connected to the evacuation line (40).

[0072] In a 32ndaspect according to any one of the previous aspects, the main fluid line (3) comprises a delivery tract (30) located downstream of the main pump (6) and up to the outlet point (5), particularly interposed between the second filter (26) and the outlet point (5).

[0073] In a 33rdaspect 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).

[0074] In a 34thaspect 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 main pump (6) - specifically the outlet (26b) of the second filter (26) - and the outlet point (5) and configured to selectively prevent or allow a fluid flow.

[0075] In a 35thaspect 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.

[0076] The bypass conduit (33) is directly connected to common line tract (25a) in turn directly connected to the evacuation line (40).

[0077] In a 36thaspect 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).

[0078] Notably the delivery valve (V8) is located upstream of the closure valve (V7).

[0079] In a 37thaspect 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.

[0080] In a 38thaspect 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 effluent from the patient, to the drain (27).

[0081] In a 39thaspect according to any one of the previous aspects, the apparatus further includes a supporting structure (37) housing: o the fluid circuit (2), o a first dosing pump (11), o a second dosing pump (16), o the main pump (6), and o a plurality of valves (V1 to Vn).

[0082] In a 40thaspect 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 for delivery to a PD cycler.

[0083] In 41staspect 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 stored in an external container for use.

[0084] 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. 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.

[0085] In a 42ndindependent aspect which may be combined with any of the previous aspects, a medical tubing set (63) is provided comprising: a supply line (64) having one end (64a) for a connection to a medical fluid generation apparatus (1); a container (65) with a port (65a); a container line (66) having one end (66a) connected or configured to be connected to the port (65a) of the container (65); a cassette (68) comprising a first inlet port (HB), a patient line port (PL) and a drain line port (DL), a cassette line (67) having one end (67a) connected or configured to be connected to the first inlet port (HB) of the cassette (68), a patient line (73) connected to the patient line port (PL); a drain line (74) connected to the drain line port (DL); wherein a second end (64b) of the supply line (64), a second end (66b) of the container line (66) and a second end (67b) of the cassette line (67) are in fluid communication with each other, in particular at a tube fitting (69). For example, the tube fitting (69) may be a “Y” junction, e.g., where the leg of the Y is connected to the supply line (64) and the two inclined arms are respectively connected to the container line (66) and the cassette line (67).

[0086] In one embodiment, the container (65) may be a container heater bag, namely a bag suitable to be heated together with the contained fluid before fluid delivery to the cassette (68).

[0087] In a 43rdindependent aspect which may be combined with any of the previous aspects, a medical tubing set (63) is provided comprising: a supply line (64) having one end (64a) for a connection to a medical fluid generation apparatus (1); a container (65) with a port (65a); a container line (66) having one end (66a) connected or configured to be connected to the port (65a) of the container (65); a cassette line (67) having one end (67a) connected or configured to be connected to a cassette (68) for a medical treatment,wherein a second end (64b) of the supply line (64), a second end (66b) of the container line (66) and a second end (67b) of the cassette line (67) are in fluid communication with each other, in particular at a tube fitting (69).

[0088] In a 44thaspect according to any one of the previous two aspects, the container (65) is a bag, in particular a flexible plastic bag.

[0089] In a 45thaspect according to any one of the previous three aspects, the medical tubing set (63) further comprises a clamp (70) positioned on the cassette line (67).

[0090] In a 46thaspect according to any one of the previous four aspects, the container line (66) is irremovably connected to the container (65).

[0091] In an 47thaspect according to any one of the previous five aspects, the container line (66) has a length of at least 50 mm, and particularly of at least 100 mm.

[0092] In a 48thaspect according to any one of the previous aspects 42-45 and 47, the end (66a) of the container line (66) is provided with a container connector (80) to allow removable connection connected to the port (65a) of the container (65), optionally further comprising a clamp (81) positioned on the supply line (64).

[0093] In a 49thaspect according to any one of the previous seven aspects, the medical tubing set (63) further comprises an auxiliary cassette line (85) having one end (85a) connected or configured to be connected to the cassette (68) for a medical treatment, wherein a second end (85b) in fluid communication with the supply line (64) and / or the container line (66), in particular at an auxiliary tube fitting (86).

[0094] In a 50thaspect according to the previous aspect, (I) the supply line (64) and the container line (66) are connected at respective first and second port of a tube fitting (69), (II) the cassette line (67) and the auxiliary cassette line (85) are connected at respective first and second port of an auxiliary tube fitting (86), one further port (69a) of the tube fitting (69) being in fluid communication with one further port (86a) of the auxiliary tube fitting (86).

[0095] In a 51staspect according to any one of the previous nine aspects, the medical tubing set is a disposable set.

[0096] In a 52ndaspect according to any one of the previous ten aspects, the medical tubing set is for a peritoneal dialysis treatment.

[0097] In a 53rdaspect according to any one of the previous eleven aspects, the medical tubing set (63) further comprises the cassette (68) having a first inlet port (HB) for receiving the end (67a) of the cassette line (67), in particular wherein the cassette line (67) is irremovably connected to the cassette (68).

[0098] In a 54thaspect according to the previous aspect, the cassette (68) comprises a patient line port (PL), a patient line (73) connected to the patient line port (PL), a drain line port (DL), a drain line (74) connected to the drain line port (DL) and at least one fluid chamber (71) and optionally two fluid chambers (71, 72), enabling a pumping mechanism, which, in one phase, receives fluid from the first inletport (HB) and, in a second phase, directs the fluid towards the patient line port (PL), in particular a clamp (77) being provided on the patient line (73).

[0099] In a 55thaspect according to the previous aspect, the patient line (73), the drain line (74) are irremovably connected to the cassette (68).

[0100] In a 56thaspect according to any one of the previous three aspects, the cassette (68) further comprises a last fill line port (LF) and a last fill line (75) connected to the last fill line port (LF), optionally the set further comprising a clamp (76) positioned on the last fill line (75).

[0101] In a 57thaspect according to any one of the previous four aspects, the cassette (68) comprises a second inlet port (SL), a bag supply line (78) configured to be connected to a bag of fresh medical fluid. In case this bag supply line (78) is present, the medical tubing set (63) may be used with prepackaged bags of medical fluid instead of (or in addition to) receiving the medical fluid from the medical fluid generation apparatus. Indeed, the medical fluid may arrive from the fresh bag through the bag supply line directly to the cassette (68). From the cassette (68), the fresh fluid (eventually already heated) may be directed to the patient or, alternatively, it may be directed to the container (65) for example to be heated and then directed to the patient.

[0102] In a 57thbis aspect according to the previous aspect, the bag supply line (78) includes a branch connector (93) to connect the bag supply line (78) to a plurality of branch supply lines (78a, 78b), each branch supply line being configured for connection to a respective bag of fresh medical fluid. This configuration allows to use a plurality (two or more) bags of fresh medical fluid to run the treatment instead of (or in addition to) using the medical fluid produced by the medical fluid generation apparatus.

[0103] In a 57thter aspect according to any one of the previous four aspects 53 to 56, the cassette (68) comprises a second inlet port (SL), a sampling container (89) and a sampling line (78) connected to the second inlet port (SL) and to the sampling container, in particular a clamp (79) being provided on the sampling line (78).

[0104] In a 58thaspect according to any one of the previous five aspects, the drain line (74) comprises a drain connector (82) and the supply line (64) comprises a supply connector (83), wherein the drain connector (82) and the supply connector (83) are configured to be connected directly to each other or, alternatively, the set comprising an intermediary element (84), such as a twin protective cap, the intermediary element (84) being simultaneously connectable to both the drain connector (82) and the supply connector (83) to define connected supply and drain lines.

[0105] In a 59thaspect according to any one of the previous six aspects when depending on aspects 20 or 21 , the cassette (68) comprises a second inlet port (SL), the auxiliary cassette line (85) being connected, in particular irremovably, to the second inlet port (SL).

[0106] In a 60thaspect according to any one of the previous aspects 42 to 59, the medical tubing set (63) further comprises at least one sterilizing grade filter (92) located downstream of the end (64a)of the supply line (64). The sterilizing grade filter can be located on any one of the supply line (64), the container line (66), the cassette line (67), and the patient line (73).

[0107] In a 61staspect according to the previous aspect, the at least one sterilizing grade filter (92) is located on the supply line (64). The fluid flowing along the supply line (64) crossing the filter membrane and, if already not sterile, becoming sterile fluid.

[0108] In a 62ndaspect according to any one of the previous two aspects, the medical tubing set (63) comprises a first and a second sterilizing grade filter located downstream of the end (64a) of the supply line (64), the first sterilizing grade filter 92a being located on the supply line (64), the second sterilizing grade filter 92b being located on any one of the supply line (64), the container line (66), the cassette line (67), and the patient line (73).

[0109] In a 63rdaspect according to any one of the previous three aspects, the at least one sterilizing grade filter (92) includes a membrane with mean pore diameter less than one micrometer, such as 0.1-0.5 micrometer, e.g. 0.1 or 0.2 micrometer.

[0110] In a 64thaspect according to any one of the previous four aspects, the at least one sterilizing grade filter (92) includes no venting.[0011 1] In a 65thindependent aspect an assembly is provided comprising: the medical fluid generating apparatus (1) according to any one of the aspects 1 to 42; and the medical tubing set (63) according to any one of the aspects 43 to 59, wherein the supply line (64) has one end (64a) fluidly connected to an outlet port (5) of the medical fluid generation apparatus.

[0112] In a 66thaspect according to the previous aspect, the medical tubing set (63) comprises: a supply line (64) having one end (64a) fluidly connected to an outlet port (5) of the medical fluid generation apparatus (1); a container (65) with a port (65a); a container line (66) having one end (66a) connected to the port (65a) of the container (65); a cassette (68); a cassette line (67) having one end (67a) connected to the cassette (68); wherein a second end (64b) of the supply line (64), a second end (66b) of the container line (66) and a second end (67b) of the cassette line (67) are in fluid communication with each other, in particular at a tube fitting (69), and wherein the pressure sensor (P2) is configured to sense a pressure of the medical fluid in the container line (66).

[0113] In a 67thaspect according to the previous aspect, in the no-flow condition, no medical fluid is flowing from the container (65) to the cassette (68) via the cassette line (67).

[0114] In a 68thaspect according to any one of the previous two aspects, in the no-flow condition, the container (65) is filled with medical fluid.

[0115] In a 69thaspect according to any one of the previous three aspects, in the medical fluid usage condition, the medical fluid is flowing from the container (65) to the cassette (68) via the cassette line (67).

[0116] In a 70thaspect according to any one of the previous four aspects, during step (iv) medical fluid flows to the container (65).

[0117] In a 71staspect according to any one of the previous five aspects, during the first medical fluid supply to the external medical device (101) medical fluid is provided to the container (65).

[0118] In a 72ndaspect according to any one of the previous six aspects, the no-flow pressure corresponds to a pressure level in the container line (66) when the container has been filled with medical fluid.

[0119] In a 73rdaspect according to any one of the previous seven aspects, the external medical device (101) comprises the medical tubing set (63) and / or a PD cycler (23).

[0120] In a 74thaspect according to any one of the previous seven aspects, the assembly further comprises a PD cycler (23), the cassette (68) of the medical tubing set (63) being coupled or configured to be coupled to the PD cycler (23).

[0121] 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 also in case there is neither electric connection, nor communication between the two apparatuses.

[0122] 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, to be supplied to a cycler, wherein the cycler requires no modification or minimum modifications to work with the apparatus.

[0123] It is a further advantage of the present disclosure to provide an assembly including the apparatus and a medical tubing set that cooperate together to allow interfacing the apparatus with standard cyclers.

[0124] 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

[0125] Figure 1 is a schematic view of a fluid circuit of a medical fluid generation apparatus according to an embodiment of the description;

[0126] Figures 2A to 2E are embodiments of a disposable medical tubing set;

[0127] Figure 3 is a schematic view of a disposable medical tubing set made of a first disposable part with a cassette known in the dialysis field and of a second disposable part that is an adapter to make the tubing set configured for use with the medical fluid generation apparatus, for example, of Figure 1 ;

[0128] Figure 4 is a schematic view of an assembly of a medical fluid generation apparatus and a disposable medical tubing set according to a first embodiment;

[0129] Figure 4A is a schematic view of the assembly of Figure 4, in a medical fluid usage condition.

[0130] Figure 5 is a schematic view of an assembly of a medical fluid generation apparatus and a disposable medical tubing set according to a second embodiment;

[0131] Figure 6 is a recorded pressure signal during a patient fill phase;

[0132] Figure 6A is an enlarged view of the pressure signal of figure 6;

[0133] Figure 7 is a recorded pressure signal, measured for a full PD cycle including fill, dwell and drain;

[0134] Figure 8 is a flow chart representing steps performed by the medical fluid generation apparatus to execute the steps described in the present disclosure.DETAILED DESCRIPTION

[0135] The medical fluid generation apparatus

[0136] 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, is schematically outlined.

[0137] 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.

[0138] 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., nondisposable) 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.

[0139] 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.

[0140] 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.

[0141] In an alternative embodiment (not shown), 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.

[0142] 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).

[0143] The supporting structure 37 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 within the 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.

[0144] 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.

[0145] 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.

[0146] 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.

[0147] 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.

[0148] 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.

[0149] 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 main fluid 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 externaladditional 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.

[0150] Considering the shown embodiment, 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.

[0151] Differently from what is represented in the embodiment of figure 1, the first concentrate container 9 may instead have two ports in fluid communication with the main fluid line 3 of the fluid circuit 2 at two different locations, particularly when the first concentrate container 9 contains a dry concentrate to be dissolved prior to use.

[0152] 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. Alternatively, the second concentrate container 14 may instead have two ports 13, 53 in fluid communication with the main fluid line 3 of the fluid circuit 2 at two different locations, particularly when the second concentrate container 14 contains a dry concentrate to be dissolved prior to use.

[0153] Regardless the specific embodiment, the ports 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 provided on the supporting structure 37. Therefore, the container accesses 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. Any configuration with both dry and liquid concentrates in the required number is encompassed by all the embodiments of the present description.

[0154] Referring now specifically 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 of 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.

[0155] 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.

[0156] 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 ]2 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.

[0157] 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; 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.

[0158] 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 medical device, such as a container 68 and / or 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, 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 passage valve V15, which is described below. For example, the first injection point j1 is implemented as three-way valve. 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.

[0159] 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 ]2 located between the inlet point 4 and the outlet point 5. More specifically, the second injection point ]2 is located downstream of the water inlet valve V3 and the pressure regulator 41. Furthermore, the second injection point ]2 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 ]2 is also downstream of a passage valve V15, which is described below. For example, the second injection point ]2 is implemented as three-way valve. When it comes to thedownstream 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.

[0160] 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.

[0161] A pre-mixing mixing chamber 20 (or 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 ]2 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 j 1, ]2. 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 and in an embodiment is not present.

[0162] 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 j1 and the second injection point ]2). 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.

[0163] 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 T1 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.

[0164] 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.

[0165] The main mixing chamber 17 is placed on the main fluid line 3 and located downstream of the first injection point ]1 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. The mixing chamber 17 has a service line 32 connected to its top portion and directs fluid, gas or a combination of fluid and gas towards valve V6, which is used to selectively open the service line 32.

[0166] 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 j 1 , the second injection point ]2, 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 ]2 towards the outlet point 5. Pump 6 does not need to be driven in the reverse direction (i.e., fluid flow directed from the pump 6 towards the injection points j1, ]2), nor does it allow such a fluid flow. In other embodiments, the main pump 6 may run in both directions.

[0167] 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.

[0168] 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.

[0169] 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.

[0170] 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 fluidgeneration 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, sensor 18 belongs to the protective / supervisory system while sensor 31 belongs to the control system.

[0171] 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 temperature of the fluid flowing in the main fluid line 3 at different locations, usually in respective close proximity to the respective sensor 18, 31).

[0172] 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, at a diverting point 47, 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 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. In more detail, during execution of a concentrate mixing sequence for the first or the second concentrate, the control unit 19 controls 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, the mixing chamber 17, the diverting point 47, and the evacuation line 40 routing the fluid towards a drain 27. 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 concentrate mixing sequence no fluid is flowing in the terminal portion 49.

[0173] 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.

[0174] 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.

[0175] 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 the opening / 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).

[0176] 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.

[0177] 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.

[0178] 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 medicalfluid 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.

[0179] 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 V11 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.

[0180] 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.

[0181] 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 external medical device 101 , e.g., 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.

[0182] 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 V14 located 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.

[0183] 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 101.

[0184] 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. As can be seen in the embodiment of figure 1 , the delivery line pressure sensor P2 is located upstream of the delivery valve V8 along the direction of medical fluid flow towards the outlet point 5. As it will be clarified, when the delivery valve V8 remains open while the other valves (e.g., closure valve V7) are closed, the delivery line pressure sensor P2 senses the pressure that is present in the fluid at the outlet point 5 and, if a supply line 64 of a medical tubing set 63 is connected, the pressure inside the supply line can be sensed by the apparatus 1 .

[0185] 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 selectivelyprevent 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. A recirculation conduit 34, where a closure valve V5 is located, is also shown connecting the common line tract 25a to a position upstream the first and second injection points J1 and J2.

[0186] As visible in figure 1 showing the most effective embodiment, the fluid circuit 2 further includes a return conduit 38 connecting a return / drain port 61 , connectable to an external medical device 101 , for example to a drain line 74 of a disposable tubing set 63 part of a dialysis unit 23, to the drain 27. The external device may be connected to the return / drain port 61 and use it and the return conduit to discharge (spent) fluid to the drain.

[0187] The fluid circuit 2 also shows a water delivery 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 should it be necessary to provide water in the fluid circuit and the apparatus or out from the fluid circuit and the apparatus; in this regard, the plurality of valves comprises the passage valve V15 configured to selectively prevent or allow a fluid flow in the water recirculation conduit 36.

[0188] The medical tubing set

[0189] A medical tubing set 63 is shown in Figures 2A-2E and 3 and is generally a disposable set; the medical tubing set 63 is designed to allow use of a medical fluid generating apparatus such as the apparatus above described with an external medical device 101 , such as a PD cycler and to enhance the fluid management required for effective peritoneal dialysis. The set 63 shown in Figure 2A comprises a supply line 64 which is connectable at one end 64a to the medical fluid generation apparatus 1 via a supply connector 83, ensuring the transfer of dialysis fluid into the PD system. As shown in Figures 4 and 5, the supply connector 83 is removably engaged to a counter-connector at the outlet point 5 of the medical fluid generation apparatus 1 to allow the prepared medical fluid to flow from the medical fluid generation apparatus 1 inside the set and towards a container 65. The opposite end 64b of the supply line 64 interfaces with other lines at a junction point tube fitting 69, maintaining continuous fluid communication which is essential for the management of the fluid flow.

[0190] Integral to the system is a container 65, typically a flexible plastic bag equipped with an inlet / outlet port 65a. This container acts as a reservoir for the medical (dialysis) fluid before its introduction into the peritoneal cavity. Connected to this container 65 is a container line 66, fixed, for example irremovably, to prevent leaks and disconnections, for maintaining the sterility of the dialysis fluid. This container line 66 has a container line end 66a connected to the container port 65a and a second end 66b connected to the tube fitting 69 to be in fluid communication with the supply line 64. The container line 66has a certain length such as of at least 50 mm, providing a distance between the container 65 and the rest of the system.

[0191] A cassette line 67, in fluid communication with the tube fitting 69 at its second end 67b, connects at one end 67a to a cassette 68 that plays a central role in the dialysis process, defining when coupled to the PD cycler the flow paths from and to the patient and from and to the various connected lines. A (manual) clamp 70 on this line 67 selectively block or allow fluid flow, during e.g., the set-up of the cycler.

[0192] The cassette 68 is a rigid (plastic) support for the various connected lines that are received by respective line ports and has internal channels to redirect the fluids from and to the lines. In the specific examples, it has two chambers 71, 72 configured to be coupled / engaged to a pumping mechanism of the cycler to command and generate the fluid flows inside the cassette itself.

[0193] As mentioned, the cassette 68 is equipped with multiple ports and lines including a patient line port PL, a corresponding patient line 73, a drain line port DL, and a corresponding drain line 74 as shown in Figure 2A. Additional configurations include a last fill line port LF and a corresponding last fill line 75. Any of these lines may comprise a corresponding manual clamp (such as clamps 76 and 77 represented in the figures).

[0194] What's shown in Figure 2A is a medical tubing set design for connecting the medical fluid generating apparatus 1 to a PD cycler (such as Baxter's Claria Plus™ cycler). This design is the most basic of the various designs described below as it has no extra supply lines (and no need for additional prepackaged supply bags). The medical fluid generating apparatus 1 is capable of adjusting the fluid composition, so that there is no need to attach different types of fluid bags to the cassette, except possibly for the "last fill bag" (connected to line 75). What's normally connected there is a specific solution that might not be an enabled option for the medical fluid generating apparatus, such as a bag containing Icodextrin. If the last fill is not required with another solution, then the medical fluid generating apparatus can produce whatever fluid is required as the last fill, and there's no need to either have a last fill line 75 in the set or connect a bag to the last fill line 75.

[0195] Furthermore, the tubing set 63 of Figures 2A and 2B features irremovable connections between the lines and their respective ports on the cassette 68. These permanent connections ensure that the lines cannot be accidentally disconnected, maintaining the integrity and sterility of the entire system. Of course, removable connections can instead be provided in any or all of the lines, if this is appropriate or necessary for any reason.

[0196] The configuration of figure 2B differs from the embodiment of Figure 2A in that a sampling line 78 connected to a second inlet port SL, to provide the capability to handle other treatment needs such as collection of PD fluid samples. Indeed, the sampling line 78 emerging from the cassette 68 allows, during treatment, to automatically sample the PD fluid. This structure makes it possible to add a further capabilities and features to the set. Indeed, today the patient, if asked to collect PD effluent fluid, has to connect a collection bag on the drain line connector (82 in Error! Reference source not found.2A). Incase the sampling line 78 is part of the set 63, the patient needs simply to select from which drain cycle the sample shall be taken. With the design of Error! Reference source notfound.2B, the cycler gets the ability to sample any or all of the treatment cycles. It can be configured or requested to take as much or as little of a sample as is needed (dependent of course on the size of the sampling bag). For example, a sampling container 89, such as a bag smaller than the usual bag can be used. For example, a collection bag with a volume of 150 ml may be used.

[0197] The configuration of figure 2C differs from the embodiments of Figure 2A and 2B in that a removable container connector 80 has been added to the container line 66 going into the container (heater bag) 65. The removable container connector 80 enables removing the container 65 and replacing it with some other container / bag. This could e.g. be beneficial if there is a need for prescribing some fluid different than what the medical fluid generating apparatus 1 may produce (for example a solution containing amino acids such as Nutrineal™ from Baxter). One such bag may contain a dialysis solution enriched with amino acids, intended to be used as part of a peritoneal dialysis regimen. The amino acids are the primary osmotic agent, which may provide nutritional support to patients, especially those who may have difficulty maintaining adequate protein levels due to their kidney condition. It is not important when the patient fill with the fluid that is in the prepackaged bag occurs, indeed it can be connected to the removable container connector 80 upon need.

[0198] The alternative embodiment of Figure 2C may be used also when the medical fluid generating apparatus is not operative / down and the patient needs to run a PD treatment with pre-packaged bags, namely a standard treatment. The patient does not need to have a different medical tubing set, but he / she may use the set of Figure 2C also for the standard treatment. In this case, the medical tubing set 63 is equipped with the sampling line 78 which can be used as a supply line connection. Depending on the volume of fluid prescribed for the patient, it may be necessary to connect an extension line to the sampling line 78 before connecting any bag(s) to "multiply" the supply lines. It should be noted that, in the line set of Error! Reference source not found.2C, an additional clamp 81 positioned at the supply line 64 may be needed to use the set for the standard treatment.

[0199] In the further embodiment of Figure 2D, the medical tubing set 63 comprises, in addition to the supply line 64 connected to the medical fluid generation apparatus 1 , a bag supply line 78 connected to a second inlet port SL of the cassette 68. The bag supply line 78 is configured to receive medical fluid from at least one pre-packaged bag of dialysis fluid and to direct said fluid to the cassette 68. Through the cassette 68, the fresh fluid may be conveyed either directly to the patient or, alternatively, to the container 65 (for example a heater bag), where it may be heated before being delivered to the patient.

[0200] This configuration enables the tubing set 63 to be used not only with medical fluid prepared on-line by the medical fluid generation apparatus 1 , but also with one or more pre-filled bags of dialysis solution, or both sources in combination. In such embodiments, the disposable set becomes highlyflexible, allowing the same system to operate with different fluid sources according to clinical or practical needs.

[0201] In one version, shown for instance in Figure 20, the bag supply line 78 is a single line directly connected to the second inlet port SL of the cassette 68, while in Figure 2D a branch connector 93 is provided along the bag supply line 78 to create a branched configuration. The branch connector 93 allows the bag supply line 78 to split into a plurality of branch supply lines 78a, 78b, each configured for connection to a respective pre-packaged bag of medical fluid. This configuration makes it possible to connect two or more fresh-fluid bags simultaneously, ensuring continuity of treatment even when a single bag is depleted. The number of connected bags may vary, for instance from one up to three, four, or even more, depending on the therapy protocol and the total prescribed dialysis volume.

[0202] The bag supply line 78 may include suitable connectors, such as Luer-type fittings or spike connectors, enabling aseptic connection and disconnection of the pre-packaged bags. One or more clamps may also be positioned along the bag supply line 78 or its branches 78a, 78b to selectively open or close fluid communication with the cassette 68.

[0203] Although the embodiments with the bag supply line 78 are shown in Figures 2C and 2D, it is understood that similar configurations may also be present in the embodiments of Figures 2A, 2E, 3, and 4, even if not explicitly represented, providing consistent functionality and interchangeability across the different versions of the disposable set.

[0204] Consequently, the medical tubing set (63) described herein is configurable to operate:• with medical fluid produced on-line by the medical fluid generation apparatus 1 ;• with pre-packaged medical fluid bags connected via the bag supply line 78; or• with both sources concurrently, in various combinations.

[0205] When the medical tubing set 63 is used during online medical fluid preparation, the supply line 64 may be provided with a manual clamp 81 , for example a Borla clamp, as illustrated in Figure 2C and in other embodiments of the Figures; in this case the clamp 81 should be open, while differently, clamp (or clamps) 79 on the bag supply line / s 78 should be closed. During therapy, if the supply line 64 is not used to receive fluid from the medical fluid generation apparatus 1 , the line may remain closed by the clamp 81. Conversely, if the bag supply line 78 is to be used, the patient simply opens the clamp 79 to enable fluid communication.

[0206] For ease of use, the design may include (Borla) clamps on all relevant lines of the disposable set 63, allowing the patient to control each line individually according to the treatment configuration. This arrangement maintains a consistent and intuitive workflow for the user. In practice, the patient loads the disposable set into the cycler, initially keeping all clamps closed, then opens only the clamps of the lines connected to fluid bags or to the medical device outlet point 5, while keeping unused lines closed.

[0207] This structural flexibility enables the same disposable set to be adapted to multiple operational modes, either online fluid preparation, bag-based therapy, or mixed operation, without the need for different dedicated disposables.

[0208] An additional feature of the medical tubing set 63 is shown in Figures 2D and 2E. The supply connector 83 and the drain connector 82 may be interconnected already when the set 63 leaves the production. If the set 63 is to be sterilized with gas, the lines need to be somehow vented. One intermediary element 84 that take both connectors, as shown in figure 2E may be used. This intermediary element 84 is designed such that to vent the connection (there is a pathway from inside the line to the outside environment). The intermediary element 84 has also the aim to protect from touch contamination. In an example, the intermediary element 84 may comprise a twin protective cap with no threads inside it such that the connectors can just be pulled out when it's time for their connection to their intended ports when setting up the system. Alternatively, the two connectors 82, 83 may be directly connected to each other (as shown in figure 2D).

[0209] Another feature shown in the embodiment of Figures 2D and 2E (that may be of course applied to any of the other embodiments) is that the supply and drain connectors 83, 84 may be reconnected once the treatment is finished. This allows to remove at least one clamp that otherwise would be needed to avoid spillage when removing the medical tubing set 63 from the cycler.

[0210] Figure 3 shows a standard medical tubing set 87 for running a standard treatment with prepackaged bags (on the bottom left of the figure) together with an expansion set 88 on the right of Figure 3, circled with a dotted line and configured to allow usage of the standard medical tubing set 87 with the medical fluid generating apparatus 1 of figure 1 . As apparent, the standard set 87 has a cassette line portion 67a to be connected to the corresponding cassette line portion 67b of the expansion set 88 to define, when connected together, the cassette line 67. The container line 66 of the expansion set 88 is for connection to the container 65 port. It is noted that elements corresponding to the elements already described are included in the figure with corresponding reference numerals.[0021 1] The standard medical tubing set 87 has a drain line 74. A drain line portion 74b in the expansion set 88 may or may not be required, depending on whether the set is to be connected to the secondary port 61 of the medical fluid generating apparatus or not. In fact, in case a connection is required, the drain line portion 74b will provide the appropriate connector to the apparatus 1 .

[0212] To further enhance the system's flexibility, an auxiliary cassette line 85 extends from one supply line 64 of the cassette 68 and is capable of connecting at one end 85b to either the supply line 64 or the container line 66 through an auxiliary tube fitting 86. As shown in the expansion set 88 of Figure 3, the supply line 64 starts from the connector 83 and extend to the auxiliary tube fitting 86. Here, the auxiliary cassette line 85 branches from the supply line 64 and ends into a connector 91 for connection to line 78. This auxiliary cassette line 85 allows medical fluid to be provided to second inlet port SL whenever it is requested.

[0213] In the extension set of Figure 3, the auxiliary cassette line 85 is to be connected to the supply lines of the standard set 87 so that when the PD cycler withdraws liquid from the supply lines SL, the combination of lines from the standard set coupled to the expansion set allows the medical fluid generating apparatus to provide medical fluid through this line.

[0214] Figure 4 shows the medical tubing set 63 of Figure 2A coupled to the external medical apparatus 101 , for example the PD cycler and to the medical fluid generating apparatus 1 of Figure 1. The supply connector 83 is (removably) connected to the outlet point 5 and the drain connector 82 is (removably) connected to the secondary port 61 .

[0215] Figure 5 shows an embodiment of the medical tubing set 63 similar to the embodiment of Figure 2E coupled to the external medical apparatus 101 , for example the PD cycler, and to the medical fluid generating apparatus 1 of Figure 1 . In this embodiment, differently from the set of Figure 4, an auxiliary cassette line 85 is present connected at one end 85a directly to the cassette 68 and at the second end 85b to the auxiliary tube fitting 86. This auxiliary cassette line 85 allows medical fluid from the container 65 to be provided to second inlet port SL whenever it is requested. The supply connector 83 is (removably) connected to the outlet point 5 so that the medical fluid generating apparatus 1 may feed medical fluid to the external device 101 (for example to the container 65) and the drain connector 82 is (removably) connected to the secondary port 61 so that any spent fluid may be sent to the drain to which the medical fluid generating apparatus 1 is connected.

[0216] In some embodiments, the medical tubing set 63 further comprises at least one sterile sterilizing grade filter 92 arranged along the fluid path downstream of the connection between the medical fluid generating apparatus 1 and the disposable set.

[0217] The sterile sterilizing grade filter 92 is designed to ensure that the medical fluid delivered to the external medical device, such as a peritoneal dialysis (PD) cycler, is sterile at the point of use, irrespective of the sterility of the upstream circuit. In particular, the term "sterile sterilizing grade filter” refers to a filter capable of producing sterile fluid, typically defined as a filter that removes microorganisms from a liquid by retention on or within a porous membrane. The term "sterile” in the present context refers to the fact that the line set is provided in a sterile package and is pre-sterilized prior to use.

[0218] The sterilizing grade filter 92 may be located at any suitable position along the fluid path of the tubing set, for example on the supply line 64, the container line 66, the cassette line 67, or the patient line 73. In the shown embodiment, the sterilizing grade filter 92 is located on the supply line 64, downstream of the end 64a connected to the outlet port 5 of the medical fluid generating apparatus 1 . In this configuration, the fluid flowing along the supply line 64 crosses the filter membrane and, if not already sterile, becomes sterile before entering the downstream components of the tubing set 63.

[0219] In further embodiments, two or more sterilizing grade filters may be arranged in series or at different positions within the tubing set to provide redundancy and ensure continued fluid sterility particularly in case one filter fails. For example, a first sterilizing grade filter 92a may be placed on the supplyline 64, while a second sterilizing grade filter 92b may be located on the same supply line 64 or on any one of the container line 66, cassette line 67, or patient line 73.

[0220] The sterilizing grade filter includes a membrane with a mean pore diameter less than one micrometer, such as between 0.1 and 0.5 micrometer, for example about 0.1 pm or 0.2 pm. Such pore sizes are suitable for sterilizing grade membranes used in medical applications and effectively retain microorganisms. The filter may, for example, be a commercially available filter including the Pall I V-5 or GVS Speedflow filters such as the 0.2 pm Speedflow Ultra filter from GVS.

[0221] In certain configurations, the sterilizing grade filter 92 is implemented without a vent, for example when the medical fluid generation apparatus produces a degassed dialysis fluid and air accumulation within the filter is not expected. The absence of a vent also mitigates the use of PTFE venting materials, reducing issues related to e.g., PFAS content.

[0222] Accordingly, the inclusion of the sterilizing grade filter 92 provides a sterile fluid path from the outlet of the medical fluid generation apparatus to the patient, ensuring compliance with medical device sterility requirements and allowing the tubing set to be used safely with any fluid generation apparatus.

[0223] The working of the apparatus

[0224] The medical fluid generating apparatus 1 of the present description may produce virtually any volume of medical (dialysis) fluid. It does so by mixing concentrates and water. The fluid is produced on demand, at the site of use, and online, meaning that concentrates and water are mixed to the right / wished composition at the time of use. The medical fluid generating apparatus 1 delivers the produced medical fluid to a receiving external medical apparatus which in the following is identified in a non-limiting example as the medical tubing set 63 and the PD cycler 23.

[0225] In a standard cycler for peritoneal dialysis treatment, during the patient fill the PD cycler pulls medical fluid from the bag placed on the heater tray (also named heater bag). If only one bag is used it is placed on a cycler tray where the fluid is heated to e.g., 35-37°C. If more bags are used, the PD cycler replenishes the heater bag after a patient fill such that the cycler may heat the fluid to the desired temperature during the dwell phase (note that the heating may be active also during the replenishment and drain phases).

[0226] To let the PD cycler fluid management system as unaffected as possible when the medical fluid generating apparatus 1 is supplying the fluid instead of using pre-packaged bags, the medical fluid is pumped into an empty container 65, generally positioned on the PD cycler heater tray (see Figures 4 and 5). Of course, the container 65 may also initially be a bag containing fluid, but then the medical fluid generating apparatus 1 needs to have the information about that beforehand (this could occur e.g., if the patient uses a solution that the medical fluid generating apparatus 1 cannot produce).

[0227] Subsequently, the PD cycler pulls the medical fluid from the container 65 (in the same way it would have done from a factory produced bag). The medical fluid generating apparatus 1 replenishesthe container 65 (e.g., the heater bag) once the patient has been filled, or in sufficient time prior to the next fill.

[0228] The medical fluid generating apparatus 1 has to know the time when to fill the container 65 for the first time. This command may be handled by the patient confirming on the medical fluid generating apparatus (or on the PD cycler) that the medical tubing set 63 has been connected and is ready. Then, the subsequent fills are handled according to the procedure as disclosed here below.

[0229] To accomplish the task of replenishing the container 65 at the right time without needing any electrical communication between the PD cycler and the medical fluid generating apparatus 1 , a pressure sensor for sensing the pressure in the fluid circuit 2 is used. For example, the delivery line pressure sensor P2 that is placed close to the outlet point 5 of the medical fluid generating apparatus 1 may be used (see Figure 1 and Figures 4 and 5). The delivery line pressure sensor P2 senses the pressure of the medical fluid at the outlet point 5 of the fluid circuit 2 and sends a corresponding outlet pressure signal to the control unit 19.

[0230] As above indicated the first fill for the container 65 is provided upon command from a user. In this regard, the control unit 19 of the apparatus 1 is configured to receive the activation signal commanding the first medical fluid supply to the external medical device 101 ; the first medical fluid supply is a supply of a predetermined medical fluid volume sufficient to correctly fill the container 65. After the first medical fluid supply is completed, the control unit 19 is configured to place the apparatus in a fluid production pause mode which stops the delivery of medical fluid to the container 65, the delivery valve V8 is left open allowing a pressure at the outlet point 5 to be sensed by the pressure sensor P2. This also means that the pressure sensor P2 will sense the pressure in the supply line 64 up to the tube fitting 69 and to the container inlet of the medical tubing set 63 (see Error! Reference source not found.4). The tube fitting 69 is positioned at some suitable distance, e.g. 50 to 150 mm, from the container 65 (e.g., the heater bag).

[0231] If there is no medical fluid flow, the pressure sensed is the head height between the tube fitting 69 and the pressure sensor P2. The control unit 19 determines and stores this pressure which is a no-flow pressure based on the outlet pressure signal in a no-flow condition in which there is no medical fluid supply from the medical fluid generating apparatus 1 to the external medical device 101 (i.e., to the container 65).

[0232] When the PD cycler 23 starts using the medical fluid from the container 65, the control unit 19, based on the outlet pressure signal from pressure sensor P2, detects a pressure variation from the previously memorized no-flow pressure in a medical fluid usage condition in which there is still no medical fluid supply from the medical fluid generating apparatus 1 to the PD cycler while the medical fluid is used by the external medical device 101. In other terms, when the PD cycler is pulling from the heater bag during patient fill a measurable pressure drop is created at the tube fitting 69 interconnecting the tubes 64, 66 and 67. In other words, the pressure variation from the no-flow pressure is a pressure drop lowering the pressure signal to values below the no-flow pressure (i.e., the "no-flow pressure” will be lowered by this pressuredrop). The medical fluid generating apparatus 1 may hence, by measuring the pressure, follow the PD cycler during its fill phase.

[0233] This medical fluid usage condition is shown in Figure 4A, where the medical fluid generating apparatus 1 is in a pause mode and no medical fluid is supplied from the apparatus. The lack of fluid flow is represented by a symbol 'X' on the arrow above the supply line 64. This simply means that there is no fluid flow inside the tube, but the supply line 64 is in no way clamped or occluded as the pressure sensor P2 measures the pressure that prevails at the tube fitting 69. At the same time, a medical fluid flow from the container 65 via the container line 66 and the cassette line 67 is indicated by the arrows in the Figure. A pumping mechanism 90 of the cycler 23 is active on the two chambers 71 , 72 to provide a medical fluid flow towards the patient via the patient line 73 (see the arrow in Figure 4A). No fluid flow occurs in the drain line 74. Note that the pumping mechanism 90 inside the cycler 23 opens and closes valves to a pressure source and a pressure sink, meaning that a positive and a negative pressure can be put on the pump chambers 71 , 72 such that the membranes in the pump chambers 71 and 72 are ''pulled” and "pushed” to create a pumping action.

[0234] In one specific example (e.g., using Claria™ PD cycler from Baxter company), the PD cycler alternates filling of one of the pump chambers 71 ; 72 with fluid from the container 65, while the other one of the pump chambers 72; 71 is emptied towards the patient. In the next phase the two chambers 71 , 72 switch their roles such that the first chamber 71 is emptying its fluid towards the patient while the second chamber 72 is being filled from the container 65. In Figure 6 the pressure signal is shown during a patient fill phase. As can be seen, the control unit 19 may follow the entire patient filling phase. Figure 6A shows a portion of the signal in which the pump strokes are clearly distinguishable and it is fairly easy to count the strokes to determine the volume taken from the container 65 and delivered to the patient's peritoneum. Indeed, the control unit 19 knows or can determine a stroke volume and / or a fluid flow rate of a pumping action exerted on the pump chambers 71 , 72 of the cassette 68 by the pumping mechanism 90 of the PD cycler and, based on the monitored pressure variation over time, is configured to calculate the amount of medical fluid delivered by the PD cycler (i.e., removed from the container 65). In other terms, the medical fluid generating apparatus may follow the pumping action so that since the medical fluid generating apparatus may / will know the pump chambers volume it may calculate the filled volume (PD cycler delivered volume) at any given time. In particular, the medical fluid generating apparatus is able to determine when filling of the patient is ongoing, and to double check if the expected patient fill volume was supplied or not once the filling phase has ended. Further, another reason for estimating the filled volume is that the control unit 19 will know what volume of medical fluid to replenish the container 65 with.

[0235] It's relevant to note that the control unit 19 is also configured to determine a state of need for the medical fluid from the PD cycler based on the outlet pressure signal, wherein the state of need is determined based on a switch from the medical fluid usage condition to the no-flow condition. Indeed, once the PD cycler has completed the patient filling phase, no further medical fluid is removed from thecontainer 65 and no fluid is supplied from the medical fluid generating apparatus to the container 65. As a consequence, the pressure signal stops from oscillating as shown in Figure 6 and the pressure returns stable and closer to (but lower than) the no-flow pressure. In this situation, the control unit 19 knows that (I) the filling phase has ended and (II) how much medical fluid has been removed from the container 65. In fact, as above indicated, the monitored pressure variation over time defines the plurality of pressure oscillations, each corresponding to a pump stroke, and the control unit 19 knowing the stroke volume of the pumping action exerted by the pumping mechanism 90 of the PD cycler on the chamber / s 71 , 72 calculates the total delivered medical fluid volume and consequently the amount of medical fluid required when the state of need is determined. The total delivered medical fluid volume is obtained by multiplying the number of the plurality of pressure oscillations by the stroke volume.

[0236] As a consequence, the same control unit 19 commands a new supply of the medical fluid to the container 65 when or after the state of need is detected. The supply of the medical fluid is interrupted after a predetermined amount of medical fluid has been supplied to the container 65 (volume control) or after a condition of non-need for the medical fluid has been determined based on the outlet pressure signal (pressure control). In case of pressure control, the condition of non-need for the medical fluid is established when the outlet pressure signal is above an upper threshold (e.g., equal or above to the no-flow pressure).

[0237] Once the replacement of the fluid in the container 65 is achieved by the apparatus 1 , a further patient fill may be performed and the various described steps repeated as many times as necessary. In other words, the control unit 19 is configured to repeat cyclically and in temporal sequence the steps of (II) detecting a pressure variation from the no-flow pressure, (ill) determining a state of need for the medical fluid from the external medical device 101 and (iv) command a supply of the medical fluid.

[0238] With the medical tubing set 63 shown in Error! Reference source not found.2A, very few modification needs to be implemented to a standard PD cycler, for example the cycler should be configured not to draw any fluid from lines other than the supply line 64.

[0239] When the medical fluid generating apparatus 1 is used to supply medical fluid to a standard PD cycler implementing no modifications, the set 63 shown in Figure 5 may be used. Indeed, the medical tubing set 63 of Figure 5 includes the auxiliary cassette line 85 which connects the container 65 to the second inlet port SL of the cassette 68. When the PD cycler starts withdrawing fluids from the second inlet port SL, the medical fluid still comes from the container 65 (previously filled in with the medical fluid by the medical fluid generating apparatus). The resulting pressure signal for one entire cycle of the PD cycler is shown in Figure 7. The patient filling phase on the left of the diagram is followed by the container filling with medical fluid from the apparatus (the measured pressure is higher than during the patient filling phase). Thereafter, as the container 65 is replenished, the cycler 23 begins to draw medical fluid from the container 65 and return it back to the container 65. In more detail, the pump chambers 71 , 72 pump from and to the container 65 (e.g., the heater bag) in order to homogenize the temperature of the medical fluid in the heaterbag. This is represented by the pressure signal oscillating around the no-flow pressure value. At the end of the waffling step, the patient peritoneum is drained (the pressure is substantially stable) and the cycle may then start again.

[0240] The medical fluid generating apparatus 1 may determine when a patient treatment has ended and therefore there is no further need to refill the container for a new patient filling phase. A relatively simple solution would be to receive the number of refills required by the PD treatment as an input signal to the medical fluid generating apparatus 1. Alternatively (to further reduce the need for input / interaction with the medical fluid generating apparatus 1), the control unit 19 of the medical fluid generating apparatus 1 may determine the end of the treatment by analyzing the pressure signal from the pressure sensor P2, and in particular what happens to the pressure signal after the patient filling phase. In fact, as explained above and shown in Figure 7, after the patient filling phase, there is a replenishment phase (the average pressure value is higher in this phase, as shown); the cycler 23 then starts to draw medical fluid from the heater bag and to send it back to the heater bag (the pump chambers pump from and into the heater bag in order to homogenize the temperature in the bag). Finally, the graph shows what the pressure signal looks like as the cycler drains the patient.

[0241] In this setting, the medical fluid generating apparatus 1 would know that the treatment is finished if the filling phase is not followed by the cycler replenishment phase. However, if a last bag fill is used to use a different solution from a supply bag, then a cycler refill phase will indeed occur, but it will differ from the standard fill phase in terms of the pressure signal that is generated. The pressure difference during the cycler refill phase then provides information to the medical fluid generating apparatus 1 not to refill the heating bag at the end of the treatment. On the basis of the pressure analysis, the medical fluid generating apparatus 1 can draw a conclusion as to whether or not a further medical fluid filling of the container is necessary.

[0242] In an arrangement where the cycler is modified (using the set shown in, for example, Figure 2A), then the pressure signal due to the patient filling is moved directly to the pressure signal due to draw medical fluid from the heater bag and send it back to the heater bag. Since there is no need to perform this operation when the treatment is finished, the pressure signal will again provide an indication to the medical fluid generating apparatus 1 that the treatment is finished.

[0243] Figure 8 outlines the relevant steps of the method according to embodiments of the invention. In particular of the process for controlling the supply of medical fluid to an external device based on real-time pressure monitoring and the patient's need for fluid. The process begins with receiving an activation signal, which triggers the initial medical fluid supply to the external device. After completing this first fluid supply, the system measures the no-flow pressure essentially the baseline pressure when no further medical fluid is being supplied and the container 65 has been filled up.

[0244] As the process continues, the system detects any variations in pressure from the noflow baseline. These variations are monitored to assess the container fluid status, specifically by calculatingthe volume of fluid that has been used. This data helps determine if the external medical device 101 is in a state where medical fluid or additional fluid is required, which is identified when the system observes a switch from a fluid usage condition to a no-flow condition.

[0245] Once the need for fluid is detected, a command is sent to supply the necessary medical fluid to the external device. The system ensures that the fluid supply is interrupted after a predetermined amount of fluid has been administered to avoid over-supply, maintaining control over the correct dosage. After the fluid has been delivered, the apparatus is back to a condition of monitoring any pressure variation and the steps can be performed again for each machine cycle. This closed-loop process ensures accurate fluid management based on real-time pressure and patient needs.

[0246] One of the advantages of embodiments of the description is that basically any external medical apparatus (e.g., any PD cycler) may be supplied from the medical fluid generating apparatus. The initial fill can, as was indicated, be triggered by the patient via the apparatus or cycler interface and the handling of the PD cycler may remain the same as today with only minor, or no changes.

[0247] In a setup with PD cyclers different from the one represented in the figures, the medical fluid generating apparatus could work the same way, in particular should a receiving container, corresponding to the heater bag, be used. However, it is also relevant to note that the bag can be omitted (which is of course good from an environmental perspective) and a proper monitoring of the pressure as disclosed and claimed allows to properly supply fluid to an external medical device with no electric connection between the two entities.

[0248] In an additional embodiment, the medical fluid generating apparatus 1 includes a communication line 94 (only shown in Figure 4A as it is an optional feature) enabling the exchange of data between the medical fluid generating apparatus and an external medical device 101 , such as the peritoneal dialysis cycler. The communication line 94 can be implemented as either a wired communication link, such as an Ethernet, USB, or serial connection, or as a wireless communication link, for example Wi-Fi, Bluetooth, Zigbee, or a proprietary radio-frequency (RF) protocol.

[0249] Through the communication line 94, the control unit 19 of the medical fluid generating apparatus 1 is configured to receive data transmitted from the external medical device 101. The data may include need-state data, indicating a demand or requirement for medical fluid, and no-need-state data, indicating the absence of such demand. On the basis of this information, the control unit 19 commands or interrupts the operation of the main pump 6 and the corresponding valves of the fluid circuit 2, thereby initiating or maintaining the supply of medical fluid when or after need-state data is received, and preventing or stopping the supply when or after no-need-state data is received.

[0250] The use of the communication line 94 ensures a direct and reliable communication channel between the medical fluid generating apparatus 1 and the external medical device 101. This configuration allows synchronized and on-demand fluid generation, reducing waiting times and enabling optimized fluid management according to the treatment phase controlled by the external device 101 .

[0251] However, in this additional embodiment, the medical fluid generating apparatus 1 also comprises the above-described internal pressure-based monitoring algorithm, executed by the control unit 19, which operates independently of the communication line 94. The algorithm analyzes the outlet pressure signal detected by the pressure sensor P2 in the delivery tract 30 to determine the actual need for medical fluid based on characteristic pressure variations in the connected medical tubing set 63 and external medical device 101. The algorithm can therefore detect the state of need or no-need condition based solely on pressure behavior, even in the absence of data transmission through the communication line 94.

[0252] In situations where the communication line 94 is not available or temporarily disabled (for example, due to network interruption or physical disconnection), the control unit 19 relies exclusively on this pressure-based algorithm to determine when to supply or stop supplying medical fluid, ensuring continuous and safe operation even without direct communication between the apparatus and the external device.

[0253] In embodiments where both systems, namely the communication-based control and the pressure-based algorithm, are active, the control unit 19 is configured to compare and verify the consistency between the data received from the external medical device 101 via the communication line 94 and the results of the internal pressure-based determination. In case of discrepancy between the two determinations, such as when the communication line 94 indicates a state of no-need while the pressure signal analysis indicates a need-state, or vice versa, the control unit 19 is configured to generate an alert signal for the user and / or to suspend the operation of the main pump 6 to prevent unsafe or unnecessary fluid delivery.

[0254] This dual verification approach enhances system reliability and provides a fail-safe mechanism ensuring that the medical fluid is generated and supplied only when both the communication data and the pressure-based algorithm confirm the need. Furthermore, during normal operation where communication is available, the control unit 19 may also use the pressure-based algorithm as a selfdiagnostic function to verify the correct functioning and accuracy of the algorithm itself, thus ensuring longterm consistency of the monitoring system.

[0255] Accordingly, the combination of direct communication through the communication line 94 and the pressure-based detection executed by the control unit 19 enables a robust and flexible operation of the medical fluid generating apparatus 1 . The system can adapt automatically to both connected and nonconnected configurations of the external medical device 101 , guaranteeing operational continuity, safety, and diagnostic reliability in all treatment scenarios.

Claims

CLAIMS1. A medical tubing set (63) for peritoneal dialysis treatment comprising: a supply line (64) having one end (64a) for connection to a medical fluid generation apparatus (1); a container (65) with a port (65a); a container line (66) having one end (66a) connected or configured to be connected to the port (65a) of the container (65); a cassette (68) comprising a first inlet port (HB), a patient line port (PL) and a drain line port (DL), a cassette line (67) having one end (67a) connected or configured to be connected to the first inlet port (HB) of the cassette (68), a patient line (73) connected to the patient line port (PL); a drain line (74) connected to the drain line port (DL); wherein a second end (64b) of the supply line (64), a second end (66b) of the container line (66) and a second end (67b) of the cassette line (67) are in fluid communication with each other, in particular at a tube fitting (69).

2. The medical tubing set (63) of the previous claim, wherein the container (65) is a bag, in particular a flexible plastic bag.

3. The medical tubing set (63) of any one of previous claims, wherein the cassette (68) comprises at least one fluid chamber (71) and optionally two fluid chambers (71 , 72), enabling a pumping mechanism, which, in one phase, receives fluid from the first inlet port (HB) and, in a second phase, directs the fluid towards the patient line port (PL).

4. The medical tubing set (63) of any one of previous claims, wherein the cassette (68) further comprises a last fill line port (LF) and a last fill line (75) connected to the last fill line port (LF).

5. The medical tubing set (63) of any one of previous claims, wherein the cassette (68) comprises a second inlet port (SL) and a bag supply line (78) configured to be connected to a bag of fresh medical fluid, optionally the bag supply line (78) including a branch connector (93) to connect the bag supply line (78) to a plurality of branch supply lines (78a, 78b), each branch supply line being configured for connection to a respective bag of fresh medical fluid.

6. The medical tubing set (63) of any one of previous claims 1 to 4, wherein the cassette (68) comprises a second inlet port (SL), a sampling container (89) and a sampling line (78) connected to the second inlet port (SL) and to the sampling container.

7. The medical tubing set (63) of any one of previous claims, wherein the drain line (74) comprises a drain connector (82) and the supply line (64) comprises a supply connector (83), wherein the drain connector (82) and the supply connector (83) are configured to be connected directly to each other or, alternatively, the setcomprising an intermediary element (84), such as a twin protective cap, the intermediary element (84) being simultaneously couplable to both the drain connector (82) and the supply connector (83) to define connected supply and drain lines.

8. The medical tubing set (63) of any one of previous claims, further comprising an auxiliary cassette line (85) having one end (85a) connected or configured to be fluidly connected to the cassette (68) for a medical treatment, wherein a second end (85b) is in fluid communication with the supply line (64) and / or the container line (66), in particular at an auxiliary tube fitting (86).

9. The medical tubing set (63) of the previous claim, wherein (I) the supply line (64) and the container line (66) are connected at respective first and second port of the tube fitting (69), (ii) the cassette line (67) and the auxiliary cassette line (85) are connected at respective first and second port of an auxiliary tube fitting (86), one further port (69a) of the tube fitting (69) being in fluid communication with one further port (86a) of the auxiliary tube fitting (86).

10. The medical tubing set (63) of claims 8 or 9, wherein the cassette (68) comprises a second inlet port (SL), the auxiliary cassette line (85) being connected, in particular irremovably, to the second inlet port (SL).

11. The medical tubing set (63) of any one of previous claims, wherein the cassette line (67) is irremovably connected to the cassette (68).

12. The medical tubing set (63) of the previous claim, wherein the patient line (73) and the drain line (74) are irremovably connected to the cassette (68).

13. The medical tubing set (63) of any one of previous claims, wherein the container line (66) is irremovably connected to the container (65).

14. The medical tubing set (63) of any one of previous claims 1 to 11, wherein the end (66a) of the container line (66) is provided with a container connector (80) to allow removable connection connected to the port (65a) of the container (65), optionally further comprising a clamp (81) positioned on the supply line (64).

15. The medical tubing set (63) of any one of previous claims, wherein the container line (66) has a length of at least 50 mm, and particularly of at least 100 mm.

16. The medical tubing set (63) of any one of previous claims, wherein the medical tubing set is a disposable set.

17. The medical tubing set (63) of any one of previous claims, wherein the medical tubing set is for a peritoneal dialysis treatment.4418. The medical tubing set (63) of any one of previous claims, further comprising at least one sterilizing grade filter (92) located downstream of the end (64a) of the supply line (64).

19. The medical tubing set (63) of the previous claim, wherein the at least one sterilizing grade filter (92) is located on the supply line (64), the at least one sterilizing grade filter (92) is configured so that a fluid flowing along the supply line (64) crosses a filter membrane and, if already not sterile, becomes a sterile fluid.

20. The medical tubing set (63) of any one of claims 18 and 19, the at least one sterilizing grade filter (92) includes a membrane with mean pore diameter less than one micrometer, such as 0.1 -0.5 micrometer, e.g. 0.1 or 0.2 micrometer.21 . The medical tubing set (63) of any one of claims 17 to 20, the at least one sterilizing grade filter (92) includes no air vent.

22. The medical tubing set (63) of any one of previous claims, further comprising a clamp (70) positioned on the cassette line (67) and / or a clamp (77) positioned on the patient line (73).

23. An assembly comprising:• a medical fluid generation apparatus (1) comprising: a fluid circuit (2) having an inlet point (4) for receiving water and an outlet point (5) for delivering of a medical fluid to an external medical device (101), a main pump (6) located on the fluid circuit (2) to cause a flow of the medical fluid; a pressure sensor (P2) for sensing the pressure in the fluid circuit (2); a control unit (19) configured to operate the main pump (6) and in communication with the pressure sensor (P2) to receive an outlet pressure signal from the pressure sensor (P2) indicative of a pressure of the medical fluid downstream of the pressure sensor (P2), in particular at the outlet point (5) of the fluid circuit (2) and downstream of it in a supply line connected to the outlet point (5), and the medical tubing set (63) according to any one of the claims 1 to 22, wherein the supply line (64) has one end (64a) fluidly connected to the outlet port (5) of the medical fluid generation apparatus.45

Images