Extracorporeal blood treatment device

Abstract

An extracorporeal blood treatment device 1 comprises a sampling circuit (27) having a bypass line (28) connecting at least one supply line (9) to a waste liquid line (10), acting on a fluid pump assembly (29) of the sampling circuit (27). The fluid pump assembly (29) can be driven in a first activated state, in which the fluid pump assembly (29) flows a fluid through the fluid circuit (8) from the at least one supply line (9) to the waste liquid line (10) through the bypass line (28), and in a second activated state, in which the fluid pump assembly (29) flows a fluid through the fluid circuit (8) from the at least one supply line (9) to the waste liquid line (10) through the bypass line (28). A fluid pump assembly (29) causes fluid passing through the fluid circuit (8) to flow from the waste fluid line (10) to the at least one supply line (9) through the bypass line (28). A concentrate sensor (30) is placed on the bypass line (28) for monitoring a detectable concentration of a substance into the fluid passing through the fluid circuit (8). A control unit (100) is operably connected to the concentration sensor (30) and the fluid pump assembly (29) and is configured to drive the fluid pump assembly (29), receive a signal from the concentrate sensor (30) and determine a concentration (Csup, Ceff) of the substance in a first activated state or a second activated state.

Description

Background Technology

[0001] This disclosure relates to an extracorporeal blood processing device configured to perform extracorporeal blood processing such as dialysis fluid processing.

[0002] The human kidney system can fail for various reasons. Kidney failure causes several physiological disorders. It becomes impossible to balance water and minerals or excrete the daily metabolic load. Toxic metabolic end products such as urea, creatinine, and uric acid may accumulate in the patient's blood and tissues.

[0003] Dialysis is used to treat declining kidney function, and most importantly, kidney failure. Dialysis removes waste products, toxins, and excess water from the body that would otherwise be removed by normally functioning kidneys. Dialysis, used to replace kidney function, is important for many people because it is life-saving. Treatments for kidney failure include, for example, hemodialysis (HD), hemofiltration (HF), and hemodiafiltration (HDF).

[0004] The device of the present invention can also be used in cases of continuous renal replacement therapy (CRRT) with or without anticoagulation, such as CRRT with or without systemic anticoagulation (e.g., heparin) / with or without local anticoagulation (e.g., citrate).

[0005] Regardless of the type of treatment and / or process involved, online sensing technology plays a crucial role in the efficient operation of extracorporeal blood processing devices.

[0006] For example, a general concept of providing a single (e.g., concentration) sensor is known from some existing art literature. This single sensor is placed on a bypass line extending between fresh dialysate and waste dialysate and is configured to measure the properties of fresh dialysate and used dialysate.

[0007] Patent document US2014190876 relates to a system and method for utilizing an adsorbent cartridge and quantifying the chemical changes that occur as dialysate passes through the material layers of the cartridge as a means of determining the solute concentration in the solution flowing through the cartridge. The disclosed system and method can be used to manage blood urea and quantify urea clearance during dialysis treatment, which also includes hemodialysis, hemodiafiltration, hemofiltration, and peritoneal dialysis. A fluid circuit equipped with a single conductivity sensor is effective on a bypass circuit connected in parallel with the dialyzer. The bypass circuit allows a portion of the dialysate around the dialyzer to be diverted to re-enter the flow path in the post-dialysisr flow path.

[0008] Patent document US5399157 discloses a method and apparatus for checking the operation of a sensor in a dialysis fluid circuit located in an artificial kidney. The method includes circulating a reference fluid having known properties in an extracorporeal blood circuit, checking at least one property of the dialysis fluid passing through the sensor by measurement, calculating a theoretical value for at least one property of the reference fluid based on the measurement, comparing the calculated theoretical value with a known value of said property of the reference fluid, and concluding that the sensor is functioning normally after the measurement has been performed when the calculated theoretical value is substantially equal to the known value.

[0009] Patent document US5744031 discloses an artificial kidney comprising a measuring structure for measuring the physical properties of fresh dialysis fluid and used fluid. The measuring structure is disposed in a portion of tubing shared by a branch loop of the supply line to fresh dialysis fluid and a branch loop of the discharge line to used fluid. An occlusion structure allows the fluid to circulate only in one or the other branch loop. Due to this arrangement, the physical properties of the patient's blood can be calculated, and the operation of the kidney can be permanently adjusted to a treatment goal set by the physician.

[0010] Patent document US6623442 discloses a dialysis device comprising a dialysate circuit for circulating sodium chloride and sodium bicarbonate through a hemodialyzer and a circuit for infusing a solution containing at least one ionic substance to a patient. A dialysis rate detector determines the actual dialysis rate of sodium by the hemodialyzer, and a flow rate detector determines the flow rate of the infusion solution, such that the concentration of the substance in the patient tends towards a desired concentration, which is a function of the dialysis rate, the concentration of the substance in the infusion solution, and the desired concentration.

[0011] Patent document US2014098359 discloses a method for monitoring a patient’s blood treatment, comprising the steps of: irradiating a sample of dialysis fluid used in the treatment with irradiation light of at least a first irradiation wavelength, detecting light emitted by the irradiated sample at at least a first detection wavelength, the detection wavelength being different from the first irradiation wavelength, and determining the presence and / or concentration of an analyte in the sample based on the detected light.

[0012] Patent document WO2021205389 discloses a method and system for providing personalized hemodialysis treatment to a subject. The method includes obtaining the concentrations of electrolytes and metabolites in a blood sample flowing into and out of a dialyzer through a first and a second blood bypass tube, wherein a first sensor and a second sensor are arranged in the first and second blood bypass tubes. The method also includes obtaining the concentrations of electrolytes and metabolites in dialysate fluid flowing into and out of the dialyzer through a first and a second dialysate conduit. The first and second dialysate conduits are arranged to pass through a third sensor and a fourth sensor, respectively. The method identifies the concentration changes of electrolytes and metabolites in the obtained blood sample relative to the concentrations of electrolytes and metabolites in the obtained dialysate fluid. Summary of the Invention

[0013] This disclosure describes an extracorporeal blood processing device for performing extracorporeal blood processing, such as therapeutic plasma exchange (TPE) hemofiltration (HF), hemodialysis (“HD”), hemodiafiltration (“HDF”), and processing performed during continuous renal replacement therapy (“CRRT”).

[0014] Based on the disclosure set forth herein, and without limiting the scope of this disclosure in any way, in a first independent aspect which may be combined with any other aspect or part thereof described herein, the extracorporeal blood processing device comprises: a filtration unit having a primary chamber and a secondary chamber separated by a semipermeable membrane; an extracorporeal blood circuit including a blood extraction line connected to an inlet of the primary chamber and a blood return line connected to an outlet of the primary chamber, the extracorporeal blood circuit being configured to be connected to a patient; a blood pump acting on the extracorporeal blood circuit to pump blood through the extracorporeal blood circuit; a fluid circuit including at least one supply line and a waste line; at least one supply line being connected to an inlet of the secondary chamber and / or the extracorporeal blood circuit; a waste line being connected to an outlet of the secondary chamber; a sampling circuit including a bypass line connecting at least one supply line to the waste line; and a fluid pump assembly acting on the sampling circuit to pump blood through the waste line. The fluid pump assembly is drivable in a first active state and a second active state. In the first active state, the fluid pump assembly causes at least one fluid passing through the fluid circuit to flow from at least one supply line through a bypass line to a waste line. In the second active state, the fluid pump assembly causes at least one fluid passing through the fluid circuit to flow from the waste line through the bypass line to at least one supply line. A concentrate sensor, placed on the bypass line, is used to monitor the concentration of at least one substance that can be detected entering the at least one fluid passing through the fluid circuit. A control unit, operatively connected to the concentration sensor and the fluid pump assembly, is configured to drive the fluid pump assembly in either the first or second active state, and to receive a signal from the concentrate sensor and determine the concentration of at least one substance. Optionally, a filter is placed on the bypass line between the waste line and the fluid pump assembly or the concentrate sensor. The fluid pump assembly can also be set to an inactive state, in which the fluid pump assembly stops and / or at least one valve closes the sampling circuit and / or isolates the sampling circuit from the secondary chamber and the extracorporeal blood circuit.

[0015] In a second independent aspect, which can be combined with any other aspect or part thereof described herein, a method for monitoring at least one substance in a fluid entering a fluid circuit of an extracorporeal blood device, the extracorporeal blood device being of the type comprising a filtration unit, an extracorporeal blood circuit connected to the filtration unit, a fluid circuit comprising at least one supply line and a waste line (wherein at least one supply line is connected to the filtration unit and / or the extracorporeal blood circuit, and the waste line is connected to the filtration unit), a sampling circuit comprising a bypass line connecting at least one supply line to the waste line, a fluid pump assembly acting on the sampling circuit, and a concentrate sensor placed on the bypass line, the method comprising the following steps:

[0016] By driving the fluid pump assembly in a first activated state to allow at least one fluid passing through the fluid circuit to flow from at least one supply line through a bypass line to a waste liquid line, and by monitoring the concentration of at least one substance detectable entering the at least one fluid via a concentrate sensor; or

[0017] By driving the fluid pump assembly in the second activated state, at least one fluid passing through the fluid circuit flows from the waste liquid line through the bypass line to at least one supply line, and the concentration of at least one substance that can be detected entering the at least one fluid is monitored by the concentrate sensor.

[0018] In the following aspects, details regarding both the extracorporeal blood processing devices and methods considered in the preceding independent aspects have been added. Each aspect relating to a component / element and / or any feature of each extracorporeal blood processing device / method considered in the preceding independent aspects can be clearly combined with aspects of other extracorporeal blood processing devices considered in both the independent and dependent aspects.

[0019] In the third aspect according to any of the foregoing aspects, the concentrate sensor on the bypass line is a concentrate sensor shared by multiple substances, or the concentrate sensor on the bypass line is a concentrate sensor configured separately for each substance whose concentration is to be determined. If the concentrate sensor on the bypass line is a concentrate sensor shared by multiple substances, it is configured to measure the concentration of each of the multiple substances.

[0020] In the fourth aspect according to any of the foregoing aspects, a concentrated liquid sensor for monitoring the concentration of at least one substance in the blood is not provided on the extracorporeal blood circuit.

[0021] In the second of the fourth aspect according to any of the foregoing aspects, apart from the concentration sensor on the bypass line, no other concentrate sensor for monitoring the concentration of at least one substance (i.e., for monitoring (one or more) of the same substance) is provided on the fluid circuit.

[0022] In the fifth aspect according to any of the foregoing aspects, the fluid circuit includes: at least one supply fluid source connected to one end of at least one supply line; at least one supply pump acting on at least one supply line; optionally, a waste fluid pump acting on a waste fluid line; wherein at least one fluid is at least one supply fluid or waste fluid flowing out of a secondary chamber; a control unit operatively connected toward and to the at least one supply pump and to the optional waste fluid pump, and configured to drive the at least one supply pump and / or the optional waste fluid pump, and optionally control valves to allow at least one supply fluid to flow into the extracorporeal blood circuit and / or the secondary chamber, and to allow waste fluid to flow out of the secondary chamber.

[0023] In the sixth aspect according to aspect 5 above, the control unit is configured, or the method is used to: drive the fluid pump assembly in a first active state and acquire a signal from the concentrate sensor to determine the concentration Csup of at least one substance entering at least one supply fluid; or drive the fluid pump assembly in a second active state and acquire a signal from the concentrate sensor to determine the concentration Ceff of at least one substance entering the waste fluid.

[0024] In the second of the sixth aspects of the aforementioned aspect 5, the control unit is configured, or the method is used to: drive the fluid pump assembly in a first active state and acquire a signal from a concentrate sensor to determine the concentration Csup of at least one substance entering at least one supply fluid; and drive the fluid pump assembly in a second active state and acquire a signal from a concentrate sensor to determine the concentration Ceff of at least one substance entering the waste fluid, wherein, in particular, the driving in the first active state and the second active state are performed sequentially in any order.

[0025] In the seventh aspect according to aspect 6 above, the control unit is configured, or the method is used to: stop at least one supply pump or keep at least one supply pump stopped, while driving the fluid pump assembly in a second active state and acquiring a signal from the concentrate sensor to determine the concentration Ceff of at least one substance entering the waste fluid.

[0026] In the eighth aspect according to aspect 6 or 7 above, the control unit is configured, or the method is used to: drive the waste liquid pump while simultaneously driving the fluid pump assembly in a second active state and acquiring a signal from the concentrate sensor to determine the concentration Ceff of at least one substance entering the waste liquid fluid.

[0027] In the ninth aspect according to any one of aspects 5 to 8 above, the control unit is configured, or the method is used to: estimate the solute removal rate J of at least one substance.

[0028] In the 10th aspect according to aspect 9 above, the solute removal rate J of at least one substance is estimated by the following procedure: receiving the flow rate Qeff of the waste liquid fluid; calculating the solute removal rate J based on the concentration Ceff of at least one substance entering the waste liquid fluid and the flow rate Qeff of the waste liquid fluid.

[0029] In the second aspect of the tenth aspect of the aforementioned aspect 10, the solute removal rate J is calculated by the following formula: J = Qeffx Ceff.

[0030] In the third aspect of the tenth aspect according to aspect 10 or aspect 10-2, the procedure for estimating the solute removal rate J of at least one substance further includes: receiving the flow rate Qsup of at least one supply fluid; and calculating the solute removal rate J based on the concentration Csup of at least one substance entering the at least one supply fluid and the flow rate Qsup of the at least one supply fluid.

[0031] In aspect 11 according to aspect 10 of the foregoing, the solute removal rate J is calculated by the following formula: J = Qeff x Ceff - Qsup x Csup; alternatively, J = Qeff x Ceff - ∑ Qsupi x Csupi, where the subscript "i" includes all or some of the fluid in the supply fluid.

[0032] In a 12th aspect according to aspect 10, aspect 10-2, aspect 10-3, or aspect 11, the control unit is configured, or the method is used, to: estimate the blood concentration Cb_est of at least one substance at the entrance of the primary chamber and / or estimate the clearance rate or dialysis rate K / D of at least one substance. Specifically, the blood concentration Cb_est of at least one substance at the entrance of the primary chamber is the plasma water concentration Cpw.

[0033] In aspect 12 of the foregoing, at least one substance is calcium, and the estimated blood concentration Cb_est is the calcium concentration in the blood. With all extracorporeal blood circuits affecting blood calcium concentration stopped, the estimated blood concentration Cb_est is consistent with the systemic calcium concentration in the patient's blood. This is a relevant parameter known during local anticoagulation or during cancer treatment using a dialysis device. Among infusions that may affect systemic calcium concentration are citrate infusions (typically pre-infusion via a blood pump) and pre-infusions of substances containing calcium ions.

[0034] In the 13th aspect according to aspect 12 or aspect 12-2, the clearance rate or dialysis rate K / D of at least one substance is estimated by the following procedure: estimating the blood concentration Cb_est of the same substance at the entrance of the primary chamber; calculating the clearance rate or dialysis rate K / D of at least one substance based on the solute removal rate J and the estimated blood concentration Cb_est of the same substance at the entrance of the primary chamber.

[0035] In the second of the 13th aspects according to aspect 12 or 13 above, estimating the blood concentration Cb_est of the same substance at the entrance of the primary chamber comprises: ensuring a balance between the concentration Ceff_eq of at least one substance entering the waste fluid and the blood concentration Cb of the same substance at the entrance of the primary chamber, such that the concentration Ceff_eq of at least one substance entering the waste fluid is equal to or proportional to the blood concentration Cb of at least one substance at the entrance of the primary chamber; optionally, Cb_est = k x Ceff_eq, where k is a balance constant function of the patient's blood parameters.

[0036] In the 14th aspect according to aspect 13 of the foregoing, balance is ensured by changing the flow rate Qsup of at least one supply fluid and / or the flow rate Qeff of waste fluid and / or the blood flow rate Qb relative to the prescription value set for extracorporeal blood treatment.

[0037] In the 15th aspect according to aspect 14 above, balance is ensured by waiting for a stabilization time after changing the flow rate Qsup of at least one supply fluid and / or the flow rate Qeff of waste fluid and / or the blood flow rate Qb.

[0038] In the 16th aspect according to aspect 15 above, adjusting the flow rate Qeff of the waste fluid and / or the blood flow rate Qb includes: reducing the ratio of the flow rate Qeff of the waste fluid to the blood flow rate Qb.

[0039] In the 17th aspect according to aspect 16 above, adjusting the flow rate Qeff of the waste fluid and / or the blood flow rate Qb includes: reducing the flow rate Qeff of the waste fluid relative to a prescription value of the flow rate Qeff of the waste fluid; optionally, the flow rate Qsup of at least one supply fluid is also reduced accordingly.

[0040] In the 18th aspect according to any one of the foregoing aspects 14 to 17, after estimating the blood concentration (Cb_est) and / or clearance rate or dialysis rate K / D, the control unit is configured, or the method is used to: move the flow rate Qsup of at least one supply fluid and / or the flow rate Qeff of waste fluid and / or the blood flow rate Qb back to the prescription value.

[0041] In the 19th aspect according to any of the preceding aspects 13 to 18 when pursuant to aspect 8, the acquisition of a signal from a concentrate sensor to determine the concentration Ceff of at least one substance entering the waste fluid is performed at least twice.

[0042] According to aspect 20 of aspect 13 of the foregoing, if extracorporeal blood treatment is hemodialysis or hemodiafiltration, balance is ensured by switching to pure ultrafiltration.

[0043] In aspect 21 according to any of aspect 14 above, the stabilization time is 2 to 20 minutes, and optionally, the stabilization time is 5 to 10 minutes.

[0044] In the second of the 21st aspect according to aspects 12 to 13, estimating the blood concentration Cb_est of the same substance at the inlet of the primary chamber comprises: recirculating at least a portion of the waste fluid from the outlet of the secondary chamber through a sampling loop and back to the inlet of the secondary chamber; measuring the concentration of said substance in the recirculated waste fluid, optionally periodically measuring the concentration of said substance in the recirculated waste fluid; waiting until the concentration of said substance becomes stable, or extrapolating the steady-state concentration of said substance; the estimated blood concentration Cb_est of the substance at the inlet of the primary chamber is a stable concentration or an inferred steady state, or derived therefrom; optionally, setting a valve in an appropriate state to guide the waste fluid; optionally, recirculation requires activation of the fluid pump assembly.

[0045] In aspect 22 according to any one of aspects 13 to 20 above, the clearance rate K of at least one substance is calculated by the following formula: K = J / (Cb_est) or the dialysis rate D of at least one substance is calculated by the following formula: D = J / (Cb_est - Csup), where Csup is the concentration Cdia of at least one substance entering the dialysis fluid.

[0046] In aspect 23 according to any one of aspects 13 to 21 above, the blood concentration Cb of at least one substance at the entrance of the primary chamber is the plasma water concentration Cpw, and the clearance rate or dialysis rate Kpw / Dpw is referred to as the plasma water concentration Cpw.

[0047] In the 24th aspect according to any one of aspects 1 to 24 above, at least one supply line includes: a dialysis line connected to the inlet of a secondary chamber; a dialysis pump acting on the dialysis line; a dialysis fluid source connected to one end of the dialysis line; and / or at least one supply line including: at least one alternative infusion line connected upstream or downstream of the filtration unit to an extracorporeal blood circuit, or directly connected to the patient; at least one alternative infusion pump acting on at least one alternative infusion line; and at least one replacement solution source connected to one end of at least one alternative infusion line.

[0048] Of course, one or more of the aforementioned supply lines may coexist on the device.

[0049] In aspect 25 according to aspect 24 above, the bypass line connects at least one alternative infusion line to the waste liquid line.

[0050] In the 26th aspect according to aspect 24 above, the bypass line connects the dialysis line to the waste fluid line, and the bypass line further includes a supply line that connects at least one alternative infusion line to the bypass line, optionally at a location between the dialysis line and the concentrate sensor.

[0051] In aspect 27 of the aforementioned aspect 25, the control unit is configured, or the method is used, to: direct the replacement solution to a bypass line.

[0052] In the second of the 27th aspects of the aforementioned aspect 26, the control unit is configured, or the method is used to: optionally, guide the replacement solution to the supply line via at least one valve or clamp.

[0053] In aspect 28 according to aspect 25 or 27 above, the replacement solution flows in a bypass line by suction applied by a fluid pump assembly.

[0054] In the second aspect 28 according to aspect 26 or 27 above, the replacement solution flows in the supply line by suction applied by a fluid pump assembly.

[0055] In aspect 29 according to any two of aspects 25 to 28 above, the control unit is configured, or the method is used to: drive the fluid pump assembly and acquire a signal from the concentrate sensor in a first activated state to determine the concentration of at least one substance Cr entering the replacement solution and / or determine the concentration of at least one substance Cdia entering the dialysis fluid.

[0056] In the second of aspect 29, which is based on any of aspects 24 to 26 when pursuant to aspect 21, recirculating at least a portion of the waste fluid comprises: stopping the dialysis pump or keeping the dialysis pump running.

[0057] In the third aspect of the 29th aspect of the foregoing, at least a portion of the recirculated waste fluid includes driving the fluid pump assembly to a maximum flow rate.

[0058] In aspect 29, or aspect 29, or aspect 29, or aspect 29, recirculating at least a portion of the waste fluid includes: maintaining the blood flow rate and alternative infusion flow rate upstream of the filtration unit at corresponding prescription values, stopping the dialysis flow rate and alternative infusion flow rate downstream of the filtration unit, and setting the waste fluid flow rate to balance the alternative infusion flow rate upstream of the filtration unit.

[0059] In the 30th aspect according to any one of aspects 1 to 29 above, the control unit is configured, or the method is used, to flush the bypass line by driving the fluid pump assembly.

[0060] In the 31st aspect according to any one of aspects 1 to 30 above, the fluid circuit further includes: an auxiliary source of auxiliary fluid connected to a bypass line at a location between at least one supply line and a concentrate sensor; optionally, the fluid circuit further includes an auxiliary line connecting the auxiliary source to the bypass line at a location between at least one supply line and a fluid pump assembly, or connecting the auxiliary source to the bypass line at a location between at least one supply line and a concentrate sensor.

[0061] In the 32nd aspect according to aspect 31 above, the control unit is configured, or the method is used, to: drive a fluid pump assembly, and optionally, control a valve to allow auxiliary fluid to flow through a bypass line.

[0062] In the 33rd aspect according to aspect 31 or 32 above, the auxiliary fluid is a flushing fluid, and the bypass line is flushed when the auxiliary fluid flows through the bypass line.

[0063] In aspect 34 according to aspect 33 above, the flushing fluid is the same as the supply fluid.

[0064] In aspect 35 according to any of aspects 32 to 34 above, the auxiliary fluid is a calibration fluid, i.e., a solution of a known concentration of the substance (one or more) to be measured, and the control unit is configured to calibrate the concentrate sensor when the auxiliary fluid flows through a bypass line.

[0065] In aspect 36 according to any one of aspects 32 to 34 above, the auxiliary fluid is a fluid used for quality control, and the control unit is configured to check the quality of the concentrate sensor as the auxiliary fluid flows through a bypass line.

[0066] In aspect 37 according to any one of aspects 31 to 36 above, the sampling circuit further includes an additional conduit that connects the blood return conduit to the bypass conduit at a location between the connection point of at least one supply conduit and the auxiliary conduit.

[0067] In aspect 38, which is according to any one of aspects 31 (when aspect 31 is according to aspect 25) to 36, the sampling circuit further includes a monitoring circuit comprising a monitoring line connecting an alternative infusion line to a blood return line, a monitoring pump assembly acting on the monitoring line, a blood monitoring sensor placed on the monitoring line, and a connecting line connecting an auxiliary line to the monitoring line at a location between the blood return line and the blood monitoring sensor.

[0068] In aspect 39, according to any one of aspects 1 to 38 above, the fluid pump assembly includes a single reversible pump acting on a bypass line.

[0069] In aspect 40 according to aspect 39 above, the single reversible pump is a blocking pump.

[0070] In a second aspect of the 40th aspect according to any one of aspects 1 to 38 above, the fluid pump assembly includes: a single pump configured to pump in the same direction at all times; a first bypass branch and a second bypass branch connecting points of the bypass line located upstream and downstream of the single pump; and an assembly valve placed on the first bypass branch, on the second bypass branch and on the bypass line, wherein a control unit is configured to control the assembly valve to arrange the fluid pump assembly in a first active state or a second active state.

[0071] In aspect 41 according to any one of aspects 1 to 40 above, the control unit is configured, or the method is used to: calibrate the concentrate sensor before and / or after determining the concentration of at least one substance.

[0072] In aspect 42 according to any one of aspects 1 to 41 above, the control unit is configured, or the method is used to: flush the bypass line and the concentrate sensor before and / or after determining the concentration of at least one substance.

[0073] In aspect 43 according to any one of aspects 1 to 42 above, the valve is operable to act on at least one bypass line between a supply line and a fluid pump assembly.

[0074] In aspect 44, which is in accordance with aspect 43 and any of aspects 26, 27 or 28, the connection between the supply line and the bypass line is between the valve and the fluid pump assembly.

[0075] In aspect 45, according to any one of aspects 26, 27, 28 or 44, the supply valve is operable to act on the supply line.

[0076] In aspect 46 according to any one of aspects 31 to 38 above, the auxiliary valve is operable to act on the auxiliary pipeline.

[0077] In aspect 47, according to any one of aspects 1 to 46 above, the concentrate sensor is positioned between the fluid pump assembly and at least one supply line.

[0078] In aspect 48, according to any one of aspects 1 to 46 above, the fluid pump assembly is positioned between the concentrate sensor and at least one supply line.

[0079] In aspect 49 according to any one of aspects 1 to 48 above, the concentrate sensor is an optical sensor, and optionally, the concentrate sensor is an optical sensor using fluorescence.

[0080] In aspect 50, according to any one of aspects 1 to 48 above, the concentrate sensor is an ion-selective electrode sensor (ISE).

[0081] In the 51st aspect according to any one of aspects 1 to 50 above, the control unit is configured to control the extracorporeal blood processing device to perform extracorporeal blood processing on a patient; the control unit is configured to determine the concentration of at least one substance or monitor at least one substance during or by temporarily interrupting extracorporeal blood processing.

[0082] In aspect 52, according to any one of aspects 1 to 51 above, the sampling circuit is disposable or part of a disposable kit, or can be connected to a disposable kit, the disposable kit including an extracorporeal blood circuit and a fluid circuit.

[0083] In the 53rd aspect according to aspect 52 above, the device includes a machine for extracorporeal blood processing and a disposable kit having a sampling circuit, the machine including a control unit and an actuation device (e.g., a pump), and electronic devices, the machine including elements for connecting the disposable kit and the sampling circuit to the machine or disconnecting the disposable kit and the sampling circuit from the machine.

[0084] In aspect 54 according to any one of aspects 1 to 53 above, at least one substance may be urea, creatinine, uric acid, glucose, electrolytes (such as Na, K, Ca, Mg), chloride, phosphate, lactate.

[0085] In the 55th aspect of 38 or in the 55th aspect of any other aspect of 38, the blood monitoring sensor is configured to detect bicarbonate, pH, pCO2, and pO2.

[0086] In aspect 56 according to any of the foregoing aspects, the monitoring method of independent method aspect 2 is used to monitor at least one substance entering a fluid that flows through a fluid circuit of an extracorporeal blood device designed for cancer dialysis treatment. Specifically, the at least one substance is calcium.

[0087] In aspect 57 according to any of the foregoing aspects, the fluid pump assembly (29) is positioned on a sampling loop (27) between at least one supply line (9, 16, 17, 18) and a waste line (10).

[0088] In the 58th aspect of any of the foregoing aspects of the combination aspect 24, the bypass line (28) is connected downstream of the dialysis pump (13) to the dialysis line (9), and in particular, the bypass line (28) is connected to the dialysis line (9) downstream of the dialysis pump (13) at a first intersection between the inlet of the dialysis pump (13) and the inlet of the secondary chamber (4).

[0089] In aspect 59 of any of the foregoing aspects of aspect 5, the bypass line (28) is connected to the waste line (10) downstream of the waste pump (14). In other aspects, the waste pump (14) is located between the outlet of the secondary chamber (4) and the connection to the bypass line (28).

[0090] In the 60th aspect according to any of the foregoing aspects of the combined aspect 5, the waste liquid line (10) extends along the length between one end connected to the outlet (4b) of the secondary chamber (4) and the other end connected to the discharge section (12) for receiving used dialysis fluid, wherein the bypass line (28) is connected to the waste liquid line (10) at a second intersection between the waste liquid pump (14) and the discharge section (12).

[0091] In aspect 61 according to any of the foregoing aspects, the circulation loop is defined by a bypass line (28), a portion of a waste line (10), a portion of a dialysis line (9), and a secondary chamber (4).

[0092] In aspect 62 of the foregoing, the circulation loop includes a fluid pump assembly (29) and a waste pump (14), optionally wherein the dialysis pump (13) is outside the circulation loop.

[0093] In the second of the 62nd aspect according to either of the two aspects mentioned above, the circulation loop further includes a concentrate sensor (30).

[0094] In the 63rd aspect according to any of the foregoing aspects, in the first activation state and / or the second activation state, the control unit (100) is configured to simultaneously activate the dialysis pump (13) and the fluid pump assembly (29) or simultaneously maintain the activation of the dialysis pump (13) and the fluid pump assembly (29).

[0095] In aspect 64 according to any of the foregoing aspects, in the first activation state and / or the second activation state, the control unit (100) is configured to simultaneously activate the dialysis pump (13), the fluid pump assembly (29) and the waste pump (14) or simultaneously maintain the activation of the dialysis pump (13), the fluid pump assembly (29) and the waste pump (14).

[0096] In aspect 65 according to any of the foregoing aspects, once the first activation state is triggered, the control unit (100) is configured to adjust the flow rate of the dialysis pump (13). In particular, the flow rate is modified to maintain the patient fluid removal rate substantially constant at a set value.

[0097] In aspect 66 according to any of the foregoing aspects, once the second activation state is triggered, the control unit (100) is configured to adjust the flow rate of the dialysis pump (13). In particular, the flow rate is modified to maintain the patient fluid removal rate substantially constant at the set value.

[0098] In aspect 67 according to any of the foregoing aspects, when the first activation state and the second activation state are triggered, the control unit (100) is configured to adjust the flow rate of the dialysis pump (13) to maintain a constant flow rate at the inlet of the secondary chamber (4), particularly relative to the processing state prior to the first activation state and / or the second activation state. In this case, the flow rate of the waste pump (14) remains constant (i.e., is not modified).

[0099] In aspect 68 according to any of the foregoing aspects, when the first activation state and the second activation state are triggered, the control unit (100) is configured to adjust the flow rate of the dialysis pump (13) in order to maintain a constant ultrafiltration rate in the filtration unit (2), in particular constant relative to the processing state prior to the first activation state and / or the second activation state, the ultrafiltration rate being defined as the flow rate difference between the flow rate at the inlet of the secondary chamber (4) and the flow rate at the outlet of the secondary chamber (4).

[0100] In aspect 69 according to any of the foregoing aspects, once the first activation state is triggered, the control unit (100) is configured to increase the flow rate of the dialysis pump (13).

[0101] In aspect 70 according to any of the foregoing aspects, once the second activation state is triggered, the control unit (100) is configured to reduce the flow rate of the dialysis pump (13).

[0102] In aspect 71 according to any of the foregoing aspects, when the first activation state is triggered, the control unit (100) is configured to maintain the flow rate of the waste liquid pump (14) unchanged, in particular unchanged relative to the processing state prior to the first activation state.

[0103] In aspect 72 according to any of the foregoing aspects, when the second activation state is triggered, the control unit (100) is configured to maintain the flow rate of the waste liquid pump (14) unchanged, in particular unchanged relative to the processing state prior to the second activation state.

[0104] In aspect 73, which is based on any of the foregoing aspects other than aspects 71 and 72, when the first activation state and the second activation state are triggered, the control unit (100) is configured to adjust the flow rates of both the dialysis pump (13) and the waste pump (14) in order to maintain a constant ultrafiltration rate in the filtration unit (2), in particular constant relative to the processing state prior to the first activation state and / or the second activation state, the ultrafiltration rate being defined as the flow rate difference between the flow rate at the inlet of the secondary chamber (4) and the flow rate at the outlet of the secondary chamber (4).

[0105] In the 74th aspect according to any of the foregoing aspects, in the first activated state, the control unit (100) is configured to activate the fluid pump assembly (29) to generate a flow rate according to a first direction from at least one supply line (9, 16, 17, 18) to the waste line (10), wherein the control unit is also configured to keep the fluid pump assembly (29) activated only along the first direction during the first activated state, and in particular, wherein the control unit is configured not to change the flow direction of the fluid pump assembly (29) during the first activated state.

[0106] In aspect 75 according to any of the foregoing aspects, in the second activation state, the control unit (100) is configured to activate the fluid pump assembly (29) to generate a flow rate in a second direction from the waste line (10) to at least one supply line (9, 16, 17, 18), wherein the control unit is also configured to keep the fluid pump assembly (29) activated only in the second direction during the second activation state, and in particular, wherein the control unit is configured not to change the flow direction of the fluid pump assembly (29) during the second activation state.

[0107] In aspect 76 according to any of the foregoing aspects, the control unit is configured to calculate calculation parameters, the calculation parameters including at least one of the following: solute removal rate (J) of at least one substance, clearance rate or dialysis rate (K / D) of at least one substance in the filtration unit (2), and concentration of the substance in the blood.

[0108] The control unit is configured to calculate the calculation parameters based on the concentration of at least one substance entering the supply fluid (Csup) and the concentration of at least one substance entering the waste fluid (Ceff).

[0109] In aspect 77 according to any of the foregoing aspects, the at least one substance is present in the supply fluid.

[0110] In aspect 78 according to any of the foregoing aspects, at least one substance is calcium or sodium.

[0111] In aspect 79 according to any of the foregoing aspects, the waste fluid line (10) extends along a length between one end connected to the outlet (4b) of the secondary chamber (4) and the other end connected to the discharge section (12) for receiving used dialysis fluid, wherein the waste fluid pump (14) is configured to deliver fluid to the discharge section (12) in a continuous manner during a first active state and a second active state.

[0112] Therefore, the objective of this disclosure is to provide an extracorporeal blood processing device configured to obtain, in a simple and reliable manner, a measurement of the concentration of substances in fluids (e.g., supply fluids, waste fluids, etc.) flowing into or out of a filtration unit.

[0113] Another objective of this disclosure is to provide an extracorporeal blood processing device configured to obtain concentration measurements in a fluid line by a direct design that is simpler and cheaper than conventional extracorporeal blood processing devices.

[0114] This disclosure also aims to provide an extracorporeal blood processing device configured to provide accurate measurements of solute removal rate and clearance rate or dialysis rate of a substance in a simple and reliable structure. In fact, the accuracy of measuring solute removal rate J from the supply / waste liquid side is higher than that from the blood side. This higher accuracy is due to the larger concentration difference between Ceff and Csup compared to the blood inlet-outlet concentration difference, and the more accurate estimation / measurement of fluid flow rate (typically based on the fluid-side scale, rather than the volumetric flow rate of a peristaltic blood pump). Another advantage of measuring J via supply / waste liquid data is that it requires no assumptions about solute distribution and possible mass transfer between red blood cells (RBCs) and plasma.

[0115] Another objective of this disclosure is to provide an extracorporeal blood processing device that is easier to monitor than conventional prior art extracorporeal blood processing devices.

[0116] Another objective of this disclosure is to provide an extracorporeal blood processing device that monitors the concentration of one or more solutes in the fluid multiple times during processing, thereby allowing for processing accuracy better than that achieved by conventional extracorporeal blood processing devices.

[0117] Additional features and advantages are described in the following detailed description and accompanying drawings, and will become apparent therefrom. The features and advantages described herein are not exhaustive; in particular, many additional features and advantages will be apparent to those skilled in the art in light of the drawings and description. Moreover, no particular embodiment need have all the advantages listed herein, and it is expressly intended that individual advantageous embodiments be claimed separately. Furthermore, it should be noted that the language used in the specification has been chosen primarily for readability and guidance purposes, and therefore does not limit the scope of the subject matter of the invention. Attached Figure Description

[0118] Figure 1 This is a schematic diagram of an extracorporeal blood processing device according to a first embodiment of the present invention;

[0119] Figure 2 This is a schematic diagram of the fluid circuit of an extracorporeal blood processing device according to a second embodiment of the present invention;

[0120] Figure 3 This is a schematic diagram of the fluid circuit of an extracorporeal blood processing device according to a third embodiment of the present invention;

[0121] Figure 4 This is a schematic diagram of the fluid circuit of an extracorporeal blood processing device according to a fourth embodiment of the present invention;

[0122] Figure 5 This is a first block diagram illustrating a monitoring method according to the present application for monitoring at least one substance entering a fluid;

[0123] Figure 6 This is a second first block diagram illustrating another monitoring method for monitoring at least one substance entering a fluid according to this application;

[0124] Figure 7 This is a third first block diagram illustrating another monitoring method according to this application for monitoring at least one substance entering a fluid;

[0125] Figure 8 This is a variant embodiment of the fluid circuit of the present invention;

[0126] Figure 9 and Figure 10 Other variations of the fluid circuit of the present invention are shown. Detailed Implementation

[0127] Extracorporeal blood processing (e.g., but not exclusively, renal failure dialysis) can be used for patients with rapidly progressing kidney function loss (called acute renal failure) or slowly deteriorating kidney function (called stage 5 chronic kidney disease (or end-stage renal disease)). In the following description, some embodiments of extracorporeal blood processing devices that are primarily (but not exclusively) suitable for or designed for intensive care treatment will be described first.

[0128] Referring to the accompanying drawings, number 1 generally refers to an extracorporeal blood processing device that can be used to perform hemodialysis (“HD”), hemofiltration (“HF”), hemodiafiltration (“HDF”), and processing performed during continuous renal replacement therapy (CRRT).

[0129] Reference Figure 1 The extracorporeal blood processing device 1 includes: a filtration unit 2 having a primary chamber 3 and a secondary chamber 4 separated by a semi-permeable membrane 5; and an extracorporeal blood circuit 6 including a blood extraction line 6a connected to an inlet 3a of the primary chamber 3 of the filtration unit 2, and a blood return line 6b connected to an outlet 3b of the primary chamber 3 of the filtration unit 2. The extracorporeal blood circuit 6 is configured to be connected to a patient "P". A blood pump 7 acts on the extracorporeal blood circuit 6 to pump blood through the extracorporeal blood circuit 6, from the patient "P" through the blood extraction line 6a to the filtration unit 2, and from the filtration unit 2 back to the patient "P" through the blood return line 6b.

[0130] The extracorporeal blood processing device 1 also includes a fluid circuit 8, which includes a dialysis line 9 and a waste fluid line 10 connected to a secondary chamber 4. One end of the dialysis line 9 is connected to the inlet 4a of the secondary chamber 4, and the other end is connected to a source 11 of dialysis fluid, such as bagged fresh dialysis fluid or a fresh dialysis fluid preparation device. One end of the waste fluid line 10 is connected to the outlet 4b of the secondary chamber 4, and the other end is connected to a discharge section 12. A dialysis pump 13 acts on the dialysis line 9 and is capable of pumping fluid into the secondary chamber 4. A waste fluid pump 14 acts on the waste fluid line 10 and is capable of withdrawing fluid from the secondary chamber 4.

[0131] An air detector (not shown) and an air separator, such as a degassing chamber 15, may be present on the blood return line 6b.

[0132] The fluid circuit 8 may also include an alternative infusion circuit comprising at least one alternative infusion line connected to the extracorporeal blood circuit 6 or directly connected to the patient "P", an alternative infusion pump acting on the alternative infusion line, and a source of replacement solution connected to one end of the alternative infusion line. Figure 1 The alternative infusion circuit shown in the embodiment includes a pre-blood pump line 16, a pre-infusion line 17, and a post-infusion line 18.

[0133] Dialysis tubing 9, pre-blood pump tubing 16, pre-infusion tubing 17, and post-infusion tubing 18 are the supply lines for fluid circuit 8.

[0134] The pre-blood pump line 16 is connected to the blood extraction line 6a upstream of the blood pump 7 and to a first source 19 (e.g., a bag) of replacement solution. The pre-blood pump 20 is located on the pre-blood pump line 16 and is capable of pumping fluid from the first source 19 into the blood circuit.

[0135] The pre-infusion line 17 is connected to the blood extraction line 6a downstream of the blood pump 7 and upstream of the filter unit 2, and is also connected to a second source 21 (e.g., a bag) of replacement solution. The pre-infusion pump 22 is located on the pre-infusion line 17 and is capable of pumping fluid from the second source 21 into the blood circuit.

[0136] The post-infusion line 18 is connected to the blood return line 6b downstream of the filtration unit 2 and to a third source 23 (e.g., a bag) for the replacement solution. The post-infusion pump 24 is located on the post-infusion line 18 and is capable of pumping fluid from the third source 23 to the blood circuit.

[0137] The fluid circuit 8 may also include one or more additional fluid lines (not shown) connected to the blood circuit and a source of at least one compensating substance or anticoagulant, as well as a pump or syringe configured to deliver the compensating substance (such as potassium or bicarbonate) at a flow rate.

[0138] The extraction pressure sensor 25 is configured to detect pressure at a measurement location in the blood extraction tubing 6a. The return pressure sensor 26 is configured to detect pressure at a measurement location in the blood return tubing 6b. The extraction pressure sensor 25 and the return pressure sensor 26 may include pressure sensing heads in the blood extraction tubing 6a and the blood return tubing 6b, respectively. The return pressure sensor 26 may be operatively coupled to the degassing chamber 15, such as... Figure 1 As shown. A monitoring valve (not shown) may be present on the blood return line 6b downstream of the degassing chamber 15.

[0139] The control unit 100 is configured to control the extracorporeal blood processing device 1 to perform extracorporeal blood processing on the patient “P”.

[0140] Control unit 100 connects to and drives blood pump 7, dialysis pump 13, waste fluid pump 14, pre-blood pump 20, pre-infusion pump 22, and post-infusion pump 24 to regulate the blood flow rate "Qb" in the blood circuit, the supply flow rate through dialysis tubing 9, the waste fluid flow rate through waste fluid tubing 10, the infusion flow rate through pre-blood pump tubing 16, the infusion flow rate through pre-infusion tubing 17, and the infusion flow rate through post-infusion tubing 18. By controlling the supply flow rate through dialysis tubing 9 and / or the waste fluid flow rate through waste fluid tubing 10, control unit 100 is also configured to control / regulate the filtration flow rate and / or patient fluid removal rate in filtration unit 2. Control unit 100 is also connected to extraction pressure sensor 25 and return pressure sensor 26 to receive signals related to pressure values ​​from these sensors 25, 26.

[0141] The control unit 100 may be an electronic control unit that includes at least a CPU, memory, and input / output devices. The control unit 100 includes or is connected to an interface 110 configured to display data and / or allow user input of data. For example, the interface includes a display, such as a touchscreen, and / or buttons or a keyboard.

[0142] Device 1 also includes a sampling circuit 27, which includes a bypass line 28, one end of which is connected to the dialysis line 9 of fluid circuit 8, and the other end of which is connected to the waste line 10 of fluid circuit 8. A fluid pump assembly 29 operates on the sampling circuit 27. A concentrate sensor 30 is placed on the bypass line 28 and configured to monitor the concentration of at least one substance that can be detected entering a fluid, which is one of several fluids passing through the bypass line 28 (i.e., one or more fluids passing through fluid circuit 8). Figure 1 In one embodiment, the fluid pump assembly 29 is a single reversible and blocking pump acting on the bypass line 28, and the concentrate sensor 30 is positioned between the fluid pump assembly 29 and the dialysis line 9. In other embodiments, not shown in the figures, the fluid pump assembly 29 may be positioned between the concentrate sensor 30 and the dialysis line 9. The sampling circuit 27, together with the fluid circuit 8 and the extracorporeal blood circuit 6, may be part of a disposable kit that can be installed on and removed from a machine for extracorporeal blood processing, which includes actuation devices such as pumps and electronics such as control unit 100. In this respect, the sampling circuit 27 may be a circuit already integrated into the disposable kit (integrated with the fluid circuit 8), or it may be separate from and connectable to the fluid circuit 8 and / or the extracorporeal blood circuit 6. The extracorporeal blood processing device 1 includes a machine for extracorporeal blood processing and a disposable kit.

[0143] The concentrate sensor 30 can be an optical sensor that provides continuous measurements and can be in permanent contact with the fluid being tested (e.g., using a fluorescent optical sensor). Alternatively, other types of sensors, such as ion-selective sensors, can be used. Typically, the concentration sensor 30 used to measure the concentration of a specific substance or for several different concentrations of several substances of interest can be of different types.

[0144] For example, concentration sensor 30 could be an ultraviolet (UV) absorption sensor that measures the absorption of UV light by the fluid. Since waste products such as urea and creatinine are removed from the blood, these products increase the UV absorption of the dialysate. By monitoring these changes, clinicians can measure the effectiveness of the dialysis treatment.

[0145] Alternatively, the concentration sensor 30 can be an ion-selective electrode (ISE) to measure specific ions in the solution. These are used to monitor specific electrolytes, such as potassium or calcium, in dialysate or patient blood.

[0146] Concentration sensor 30 can be a biosensor, i.e., a device that uses biological components (such as enzymes) to detect a specific substance. It has the potential to measure specific molecules of interest.

[0147] As described above, the concentration sensor 30 can be an optical sensor that uses optical properties to measure the concentration of a specific solute. For example, some optical sensors can detect changes in color or fluorescence related to a specific solute concentration.

[0148] Concentration sensor 30 can be a redox potential sensor to measure the reduction-oxidation potential of the dialysate. This provides insight into the chemical properties and reactions occurring in the dialysate.

[0149] The control unit 100 connects to and controls the fluid pump assembly 29 and is connected to the concentrate sensor 30 to perform a monitoring method for monitoring the concentration of at least one substance among a variety of fluids passing through the fluid loop 8. Since the desired concentration is the substance concentration, the concentration sensor is able to provide a specific concentration of that substance (e.g., calcium) without providing values ​​for other solutes such as sodium or those affected by them.

[0150] For this purpose, the control unit 100 is configured to drive the fluid pump assembly 29 in either a first active state or a second active state. In the first active state, the fluid pump assembly 29 causes fluid in the bypass line 28 to flow in one direction from the dialysis line 9 to the waste line 10. In the second active state, the fluid pump assembly 29 causes fluid in the bypass line 28 to flow in the opposite direction from the waste line 10 to the dialysis line 9. The fluid pump assembly 29 can also be set to an inactive state, in which the fluid pump assembly 29 is stopped and / or the sampling circuit 27 is isolated from the secondary chamber 4 and the extracorporeal blood circuit 6 by at least one valve.

[0151] The control unit 100 is also configured to receive a signal from the concentrate sensor 30 and to determine and monitor the concentration of at least one substance passing through the bypass line 28.

[0152] Figure 1 The apparatus 1 of the embodiment further includes a supply line 31, one end of which is connected to a post-infusion line 18 downstream of the post-infusion pump 24, and the other end of which is connected to a bypass line 28 at the connection between the dialysis line 9 and the fluid pump assembly 29. A valve 32 is operably operated on the bypass line 28 between the dialysis line 9 and the supply line 31. A supply valve 33 is operably operated on the feed line 31.

[0153] Figure 1 The device 1 of the embodiment may further include (dashed line) another supply line 34, one end of which is connected to the pre-blood pump line 16 downstream of the pre-blood pump 20, and the other end of which is connected to the bypass line 28 at the connection between the dialysis line 9 and the fluid pump assembly 29. Another supply valve 35 is operably actuated in the other supply line 34.

[0154] Figure 1 The apparatus 1 of the embodiment may further include (dashed line) another supply line 36, one end of which is connected to the pre-infusion line 17 downstream of the pre-infusion pump 22, and the other end of which is connected to the bypass line 28 at the connection between the dialysis line 9 and the fluid pump assembly 29. Another supply valve 37 is operably actuated in the other supply line 36.

[0155] In embodiments not shown, pre-infusion and post-infusion lines may be provided, i.e., infusion lines having branches that direct fluid to blood extraction and blood return lines. One end of a corresponding supply line is connected downstream of the pump 20 acting on the lines (either on a common line, on the pre-infusion branch, or on the post-infusion branch), and the other end is connected to a bypass line 28.

[0156] The first valve 38, the second valve 39, and the third valve 40 can be operably applied to the post-infusion line 18 (between the supply line 31 and the blood return line 6b), the pre-blood pump line 16 (between another supply line 34 and the blood extraction line 6a), and the pre-infusion line 17 (between another supply line 36 and the blood extraction line 6a), respectively.

[0157] Control unit 100 is configured to run software routines configured to determine or monitor the concentration of at least one substance during or by temporarily interrupting in vitro blood processing. Control unit 100 is also configured to run software routines configured to perform several monitoring methods.

[0158] According to an example of monitoring methods ( Figure 5 During extracorporeal blood processing in hemodialysis (HD or HDF), control unit 100 is configured to estimate the filter clearance or dialysis rate "K / D" of the substance using only the concentrate sensor 30 on bypass line 28. No other concentrate sensor is provided or used on the extracorporeal blood circuit 6 to monitor the concentration of the substance entering the blood and to calculate the clearance or dialysis rate "K / D".

[0159] The filter dialysis rate "K / D" is calculated under the general condition that the solute concentration in the dialysis fluid is not zero. When the solute of interest is absent in the dialysis fluid (Cdia = 0), the dialysis rate "K / D" is referred to as the clearance rate. This is typical when treating urea, uric acid, and creatinine, but may not be the case if the focus is on glucose (which may or may not be present in the supply fluid).

[0160] Control unit 100 closes or keeps supply valves 33, 35, and 37 closed, opens valve 32, and drives fluid pump assembly 29 in a first active state to allow dialysis fluid to flow from dialysis line 9 through bypass line 28 to waste line 10. Dialysis fluid interacts with concentrate sensor 30, and control unit 100 acquires signals from concentrate sensor 30 to determine the concentration "Cdia" of the substance entering the dialysis fluid.

[0161] Subsequently, in the second active state, the control unit 100 drives the fluid pump assembly 29 to allow waste fluid to flow from the waste line 10 through the bypass line 28 to the dialysis line 9, and obtains a signal from the concentrate sensor 30 to determine the concentration "Ceff" of the substance entering the waste fluid.

[0162] All fluid flow rates are generally well controlled and known to the system. Therefore, the control unit 100 receives the dialysis fluid (set or measured) flow rate "Qdia", the waste fluid (set or measured) flow rate "Qeff", and calculates the solute removal rate "J" of the substance according to the following equation: 1) J = Qeff x Ceff - Qdia x Cdia

[0163] Control unit 100 reduces the ratio of waste fluid flow rate "Qeff" to blood flow rate "Qb" within time "t" (relative to the prescription value of extracorporeal blood treatment) to ensure a balance between the concentration of the substance entering the waste fluid fluid "Ceff_eq" and the blood concentration "Cb" of the same substance at the inlet 3a of the primary chamber 3.

[0164] For example, the blood flow rate "Qb" is 200 ml / min, the prescribed value for the dialysis fluid flow rate "Qdia" is 2500 ml / h, and it decreases to a lower value of 1000 ml / h within a time interval "t" of 5 minutes. The ratio of the lower value of the dialysis fluid flow rate "Qdia" to the blood flow rate "Qb" decreases from 0.208 to 0.083.

[0165] Once equilibrium is reached, it is assumed that the concentration of the substance entering the waste fluid “Ceff_eq” is equal to the plasma water concentration of the solute of the substance at the inlet 3a of the primary chamber 3 “Cpw”, and the control unit 100 calculates the dialysis rate “Dpw” of the substance with reference plasma water concentration using the following formula: 3) pw = J / (Cpw -Cdia) = J / (Ceff_eq -Cdia) = (Qeff x Ceff - Qdia xCdia) / (Ceff_eq -Cdia)

[0166] If the goal is to report the dialysis rate "Dp" as a reference plasma concentration, the plasma solute concentration at the filter inlet can be estimated as Cp = Fp x Cpw, where "Fp" is the plasma water fraction. Therefore: 4) Dp = J / (Cp -Cdia) = J / (Fp x Ceff_eq -Cdia) = (Qeff x Ceff - Qdia xCdia) / (Fp x Ceff_eq -Cdia)

[0167] Once the waste liquid concentration "Ceff_eq" of the solute at equilibrium has been calculated, the control unit 100 stops the fluid pump assembly 29 and can also close the valve 32, and then controls the waste liquid pump 14 to increase the flow rate "Qeff" of the waste liquid fluid back to or above the prescription value to compensate for the reduction and achieve the final dosage prescription.

[0168] The blood concentration "Cb" of a substance at the entrance 3a of the primary chamber 3, such as the plasma water concentration "Cpw", can also be estimated using other standards. For example, Cb = kx Ceff_eq, where k is a balance constant function of the patient's blood parameters.

[0169] According to another embodiment, the blood concentration "Cb" of the substance at the inlet 3a of the primary chamber 3 can be estimated by a recirculation method. Based on this recirculation method and referring to... Figure 1 The dialysis pump 13 is stopped, the post-infusion pump 24 is stopped, the pre-blood pump 20 and the pre-infusion pump 22 are maintained at their prescribed values, the waste fluid pump 14 is set to balance the pre-diluted infusion and deliver the patient fluid removal rate, and the fluid pump assembly 29 is driven to the maximum flow rate so that the waste fluid is recirculated from the outlet 4b of the secondary chamber 4 through the sampling loop 27 and back to the inlet 4a of the secondary chamber 4.

[0170] The concentrate sensor 30 periodically measures the concentration of a substance in the recirculated waste fluid. The steady-state concentration of the substance is extrapolated from multiple subsequent measurements, or measurements are performed until the concentration of the substance stabilizes. The blood concentration Cb_est of the substance at the inlet 3a of the primary chamber 3 is derived from the steady-state concentration or from the extrapolated steady-state concentration. Besides calculating the filter clearance or dialysis rate "K / D", the blood concentration Cb_est can be used for other monitoring purposes.

[0171] Based on other examples of devices performing hemodialysis filtration (HDF), examine the concentrations of all supply fluids (in dialysis line 9, pre-blood pump line 16, pre-infusion line 17, and post-infusion line 18) to calculate the solute removal rate “J” using the following formula: J = Qeff x Ceff - ∑ Qsupi x Csupi; where the subscript “i” includes multiple supply fluids.

[0172] The supply fluid flow rate "Qsup" includes the dialysis fluid flow rate "Qdia" and the replacement fluid flow rate in the pre-blood pump line 16, pre-infusion line 17, and post-infusion line 18. The substance concentration to be considered "Csupi" is the concentration "Cdia" entering the dialysis fluid and the concentration of the same substance in the replacement fluid in the pre-blood pump line 16, pre-infusion line 17, and post-infusion line 18.

[0173] According to another example of the monitoring method, the control unit 100 is configured to determine the concentration of a substance in a pure waste liquid fluid.

[0174] For this purpose, the control unit 100 can be configured to drive the supply pump, while also driving the fluid pump assembly 29 in a second active state, and acquiring a signal from the concentrate sensor 30 to determine the concentration "Ceff" of the substance entering the pure waste fluid.

[0175] According to an example of monitoring methods ( Figure 6During extracorporeal blood processing, the control unit 100 is configured to determine the concentration of a substance in the replacement infusion circuit, specifically the concentration of a substance in the replacement solution of the first source 19, the second source 21, or the third source 23. This can also be performed during system setup to check fluid composition (detecting user error).

[0176] For example, to determine the concentration of a substance in the replacement solution of the first source 19, the control unit 100 closes supply valve 33 and another supply valve 37 or keeps supply valve 33 and another supply valve 37 closed, closes valve 32 or keeps valve 32 closed, opens another supply valve 35, the control unit 100 maintains the pre-blood pump 20 driven at its rated rate, and drives the fluid pump assembly 29 in a first active state to allow the replacement solution of the first source 19 to flow through supply line 34 and bypass line 28 to waste line 10. Once a predetermined volume has been pumped through loops 34 and 28, the fluid pump assembly 29 can be stopped to ensure that the fluid composition in sensor 30 fully represents the first source 19. The replacement solution of the first source 19 interacts with the concentrate sensor 30, the control unit 100 acquires a signal from the concentrate sensor 30, and determines the concentration of a substance entering the replacement solution of the first source 19.

[0177] Similarly, the concentration of the substance in the replacement solution of the second source 21 can be determined by closing the supply valve 33 and another supply valve 35 or keeping the supply valve 33 and another supply valve 35 closed, closing valve 32 or keeping valve 32 closed, opening another supply valve 37 and driving the fluid pump assembly 29 in the first active state, so that the replacement solution of the second source 21 flows to the waste liquid line 10 through the bypass line 28.

[0178] The concentration of the substance in the replacement solution of the third source 23 can be determined by closing another supply valve 35 and another supply valve 37 or keeping another supply valve 35 and another supply valve 37 closed, closing valve 32 or keeping valve 32 closed, opening supply valve 33 and driving fluid pump assembly 29 in the first active state, so that the replacement solution of the third source 23 flows to waste liquid line 10 through bypass line 28.

[0179] Figure 2 A second embodiment of the device according to the invention is shown. In this embodiment, the same reference numerals are applied to... Figure 1 The same elements as in the embodiments. With Figure 1Unlike the first embodiment, in this second embodiment, supply line 31, another supply line 34, and another supply valve 37 are not shown, but at least one may be present. The concentrate sensor 30 of this embodiment is of the type that operates intermittently on the analyte fluid, such as an ion-selective electrode sensor (ISE), which requires rinsing and calibration before and after sample measurement.

[0180] Therefore, in addition to Figure 1 The first embodiment of the second embodiment further includes an auxiliary source 41 (e.g., a bag) for auxiliary fluid, and an auxiliary line 42 connecting the auxiliary source 41 to the bypass line 28 at a location between the dialysis line 9 and the fluid pump assembly 29. An auxiliary valve 43 is operably applied to the auxiliary line 42 and is operated by the control unit 100.

[0181] In this second embodiment, the auxiliary fluid in the auxiliary source 41 may be a flushing fluid, and the control unit 100 is configured to flush the bypass line 28 and the concentrate sensor 30 before and / or after determining the concentration of at least one substance. Specifically, the flushing fluid is configured to flush the bypass line 28 while flowing through it. Flushing is performed by closing valve 32, opening valve 43, and driving the fluid pump assembly 29 in a first active state. Figure 7 The circuit is designed such that the flushing fluid is subsequently drained to the drain section 12 and is not infused into the patient “P”, so the flushing fluid can be a sterile fluid that is unsuitable for or not approved for infusion into the patient “P”.

[0182] In this second embodiment, the auxiliary fluid in the auxiliary source 41 may be a calibration fluid, i.e., a solution of the substance(s) to be measured at a known concentration, and the control unit 100 is configured to calibrate the concentrate sensor 30 before and / or after determining the concentration of at least one substance. The circuit is designed such that the calibration fluid is subsequently drained to the drain 12 and is not infused into the patient "P", therefore the calibration fluid may be a sterile fluid unsuitable for infusion into the patient "P".

[0183] In this second embodiment, the auxiliary fluid in the auxiliary source 41 can be a fluid used for quality control, and the control unit 100 is configured to control the quality of the concentrate sensor 30 before and / or after determining the concentration of at least one substance. Furthermore, the fluid used for quality control can be a sterile fluid unsuitable for infusion into the patient "P". The fluid used for quality control can be two different solutions representing the sensor's operating limits (concentrations close to the minimum and maximum concentrations requiring protection).

[0184] In this second embodiment, since the ion-selective electrode sensor (ISE) does not operate in a continuous process and requires a static state, the control unit 100 stops the fluid pump assembly 29 when the bypass line 28 is filled with the fluid to be measured (e.g., waste fluid) and the sensor 30 is filled with the fluid, and then the concentration of the substance is measured by the ISE sensor 30. The sensor technology may require stopping the fluid pump assembly 29.

[0185] In a variant embodiment, device 1 may be provided with three different bags, all of which are connected to auxiliary line 42 via valves: one bag contains flushing fluid, one bag contains calibration fluid, and one bag contains fluid for quality control.

[0186] The auxiliary source 41 and auxiliary line 42 with flushing and / or calibration and / or quality control fluids can be part of the (disposable) sampling loop 27 with the concentrate sensor 30 integrated.

[0187] Figure 3 A third embodiment of the device according to the invention is shown. In this embodiment, the same reference numerals are applied to... Figure 1 The same components as in the Chinese embodiment.

[0188] Third embodiment and Figure 2 The second embodiment is similar, but an additional line 44 is added to connect the blood return line 6b to the bypass line 28 at a location between the connection point of the dialysis line 9 and the auxiliary line 42. The additional line 44 may have a connection with the post-infusion line 18 (shown in...). Figure 1 (Middle) Public section. In addition, with Figure 1 and Figure 2 In a different embodiment, the positions of the fluid pump assembly 29 and the concentrate sensor 30 on the bypass line 28 are interchanged. In this embodiment, some calibration fluid from the auxiliary source 41 can be infused to the patient "P". A filter 45 and another valve 46 are placed on the bypass line 28 between the waste line 10 and the fluid pump assembly 29 or the concentrate sensor 12. The filter 45 is designed to prevent possible bacterial backflow and may or may not be placed.

[0189] Figure 4 A fourth embodiment of the device according to the invention is shown. In this embodiment, the same reference numerals are applied to... Figure 1 The same components as in the Chinese embodiment.

[0190] Fourth embodiment and Figure 1The first embodiment is similar, but with the addition of a monitoring loop 47, which includes a monitoring line 48 connecting the pre-infusion line 17 to the blood return line 6b. A monitoring pump assembly 49 acts on the monitoring line 48, and a blood monitoring sensor 50 is placed on the monitoring line 48. A monitoring valve 51 can be operated on the monitoring line 48 between the pre-infusion line 17 and the monitoring pump assembly 49.

[0191] The connecting pipe 52, equipped with a connecting valve 53, is located between the blood return pipe 6b and the blood monitoring sensor 50, and connects the auxiliary pipe 42 to the monitoring pipe 48.

[0192] Figure 4 This is an example involving two sensors 30 and 50, one dedicated to monitoring the fluid circuit 8 and the other dedicated to monitoring the extracorporeal blood circuit 6.

[0193] Figure 8 A variant embodiment of the fluid pump assembly 29 or monitoring pump assembly 49 is shown. The fluid pump assembly 29 includes: a single pump 54 configured to always pump in the same direction; a first bypass branch 55 and a second bypass branch 56 connecting points of a bypass line 28 located upstream and downstream of the single pump 54; and assembly valves 57, 58, 59, and 60 disposed on the first bypass branch 55, the second bypass branch 56, and the bypass line 28, wherein a control unit 100 is configured to control assembly valves 57, 58, 59, and 60 to arrange the fluid pump assembly 29 in a first active state or a second active state.

[0194] In detail, Figure 8 In this configuration, first component valve 57 operates on first bypass branch 55, and second component valve 58 operates on second bypass branch 56. Third component valve 59 operates on the bypass line 28 between the first connection point of the first bypass branch 55 to the first connection point of the bypass line 28 and the second bypass branch 56 to the first connection point of the bypass line 28. Third component valve 59 is positioned between dialysis tubing 9 and the individual pump 54. The first connection point of the first bypass branch 55 is located between third component valve 59 and dialysis tubing 9. The first connection point of the second bypass branch 56 is located between third component valve 59 and the individual pump 54.

[0195] The fourth component valve 60 operates on the bypass line 28 between the second connection point of the first bypass branch 55 to the second connection point of the bypass line 28 and the second connection point of the second bypass branch 56 to the bypass line 28. The second connection point of the first bypass branch 55 is located between the fourth component valve 60 and the single pump 54. The second connection point of the second bypass branch 56 is located between the fourth component valve 60 and the waste liquid line 10.

[0196] A single pump 54 is configured to always pump in the same direction, for example, from the third component valve 59 toward the fourth component valve 60. The control unit 100 is configured to drive the fluid pump assembly 29 in a first active state by closing the first component valve 57 and the second component valve 58 and opening the third component valve 59 and the fourth component valve 60. The control unit 100 is configured to drive the fluid pump assembly 29 in a second active state by opening the first component valve 57 and the second component valve 58 and closing the third component valve 59 and the fourth component valve 60.

[0197] Figure 9 and Figure 10 Other variations of the fluid circuit 8, in which the sampling circuit 27 is provided, are shown. Furthermore, in these circuits, the same reference numerals are applied. Figure 1 The same components.

[0198] Figure 9 This is a schematic fluid circuit for therapeutic plasma exchange (TPE). Fluid circuit 8 includes a waste fluid line 10 with a waste fluid pump 14 and a replacement line 18 with a source 23 and a pump 24 for a replacement solution. A bypass line 28 connects the waste fluid line 10 to the replacement line 18.

[0199] Figure 10 This is a schematic fluid circuit without dialysis tubing 9. Bypass line 28 connects waste fluid line 10 to post-infusion line 18.

[0200] In another embodiment, and regardless of the structure of the fluid pump assembly 29, the positions of the dialysis pump 13 and the waste pump 14 may differ from those shown in the figures. For example, as Figure 8 As shown by the dashed lines, the dialysis pump 13 can be positioned between the branch point of the bypass line 28 relative to the dialysis line 9 and the inlet 4a of the secondary chamber 4, and / or the waste pump 14 can be positioned between the discharge section 12 and the connection point of the bypass line 28 to the waste line 10. It should be noted that the fluid pump assembly 29 is positioned on the sampling loop 27 between at least one supply line 9, 16, 17, 18 and the waste line 10, and the bypass line 28 is connected to the dialysis line 9 downstream of the dialysis pump 13. Specifically, the bypass line 28 is connected to the dialysis line 9 downstream of the dialysis pump 13 at a first intersection point between the dialysis pump 13 and the inlet of the second chamber 4.

[0201] Therefore, the bypass line 28 can be connected to the waste line 10 downstream of the waste pump 14. In other respects, assuming that the waste line 10 extends along the length between one end connected to the outlet 4b of the second chamber 4 and the other end connected to the discharge section 12 for receiving used dialysis fluid, the bypass line 28 is connected to the waste line 10 at a second intersection between the waste pump 14 and the discharge section 12.

[0202] The circulation loop is defined in the fluid circuit by a bypass line 28, a portion of the waste line 10, a portion of the dialysis line 9, and a secondary chamber 4. The circulation loop includes a fluid pump assembly 29 and a waste pump 14. According to the embodiment shown in the figures, the dialysis pump 13 is external to the circulation loop. The circulation loop also includes a concentrate sensor 30.

[0203] It should be noted that in the first activated state, the control unit 100 is configured to simultaneously activate the dialysis pump 13 and the fluid pump assembly 29, or maintain the activation of the dialysis pump 13 and the fluid pump assembly 29, such that during the first activated state, fresh fluid flows from the supply line into the bypass line and toward the waste line until the discharge section. More specifically, in the first activated state, the control unit 100 can also be configured to simultaneously activate the dialysis pump 13, the fluid pump assembly 29, and the waste pump 14, or maintain the activation of the dialysis pump 13, the fluid pump assembly 29, and the waste pump 14. In this case, when fresh fluid flows from the supply line into the bypass line and toward the waste line until the discharge section, a certain percentage of the fresh fluid also flows toward the secondary chamber of the filter unit and from the filter unit toward the discharge section into the waste line.

[0204] Once the first activation condition is triggered, the control unit 100 can be configured to adjust the flow rate of the dialysis pump 13 so as not to affect blood processing. Specifically, when the first activation state is triggered, the control unit 100 can be configured to adjust the flow rate of the dialysis pump 13 to maintain a constant flow rate at the inlet of the second chamber 4 relative to the processing state prior to the first activation state. This allows the amount of fresh fluid entering the secondary chamber of the filtration unit to remain unchanged, so that the exchange rate between the fluid and blood in the filtration unit remains substantially constant. For example, when the first activation state is triggered, a portion of the fresh fluid is transferred from the dialysis tubing to the bypass tubing; therefore, it is necessary to adjust the flow rate delivered by the dialysis pump 13 to maintain a constant flow rate at the inlet of the secondary chamber.

[0205] Furthermore, when in the first activation state, the control unit 100 can be configured to adjust the flow rate of the dialysis pump 13 to maintain a constant ultrafiltration rate in the filtration unit 2 relative to the processing state prior to the first activation state and / or the second activation state. The ultrafiltration rate can be defined as the flow rate difference between the flow rate at the inlet of the secondary chamber 4 and the flow rate at the outlet of the secondary chamber 4; in fact, the ultrafiltration rate indicates the amount of fluid exchanged in the filtration unit, expressed as flow rate.

[0206] Therefore, once the first activation state is triggered, the control unit 100 can be configured to increase the flow rate of the dialysis pump 13.

[0207] In an embodiment, when the first activation state is triggered, the control unit 100 can be configured to maintain a constant flow rate of the waste pump 14 relative to the processing state prior to the first activation state. Due to the loop configuration shown in the figures and described above, simply changing the flow rate of the dialysis pump 13 is sufficient to maintain a constant ultrafiltration rate.

[0208] Conversely, according to an alternative embodiment, when the first activation state is triggered, the control unit 100 is configured to adjust the flow rates of both the dialysis pump 13 and the waste pump 14 to maintain a constant ultrafiltration rate in the filtration unit 2 relative to the processing state prior to the first activation state and / or the second activation state. Alternatively, the ultrafiltration rate can be maintained constant simply by changing the flow rate of the waste pump (keeping the flow rate generated by the dialysis pump constant).

[0209] It should be noted that, in the first activated state, the control unit 100 is configured to activate the fluid pump assembly 29 to generate a flow rate according to a first direction from at least one supply line 9, 16, 17, 18 to the waste line 10; the control unit is also configured to keep the fluid pump assembly 29 activated only along the first direction during the first activated state, wherein the control unit is configured not to change the flow direction of the fluid pump assembly 29 during the first activated state.

[0210] Once the second activation state is triggered, the control unit 100 is also configured to adjust the flow rate of the dialysis pump 13, since the inlet of the secondary chamber will receive both fresh fluid from the source 11 and used fluid from the bypass line. Therefore, once the second activation state is triggered, the control unit 100 is configured to reduce the flow rate of the dialysis pump 13; thus, the flow rate of the waste pump 14 can remain constant relative to the processing state prior to the first or second activation state, or it can be adjusted to maintain a substantially constant ultrafiltration rate.

[0211] When the second activation state is triggered, the control unit is configured to activate or maintain the activation of the dialysis pump 13 and the waste fluid pump 14, such that while a certain percentage of the used fluid is recirculated from the waste fluid line to the dialysis line through the bypass line, a certain percentage of the used fluid is continuously delivered to the discharge section, and fresh fluid is continuously delivered by the dialysis pump 13 to the inlet of the secondary chamber. Therefore, in the second activation state, the inlet of the secondary chamber of the filtration unit receives the used fluid recirculated through the bypass line and the fresh fluid supplied from source 11.

[0212] It should be noted that, in the second active state, the control unit 100 is configured to activate the fluid pump assembly 29 to generate a flow rate in a second direction from the waste line 10 to at least one supply line 9, 16, 17, 18; the control unit is also configured to keep the fluid pump assembly 29 activated only in the second direction during the second active state, wherein the control unit is configured not to change the flow direction of the fluid pump assembly 29 during the second active state.

[0213] In summary, the control unit is configured to calculate computational parameters, including at least one of the following: solute removal rate J of at least one substance, clearance rate or dialysis rate K / D of at least one substance in filter unit 2, and concentration of the substance in the blood. The control unit is configured to calculate the computational parameters based on the concentration Csup of at least one substance entering the supply fluid and the concentration Ceff of at least one substance entering the waste fluid. It should be noted that at least one substance may be present in the supply fluid contained in source 11 at a certain concentration. In detail, at least one substance may include calcium. Alternatively, other electrolytes, such as sodium, may be considered. Once the first and second activation states terminate, the control unit performs the calculation of the computational parameters. This monitoring method can be advantageously used to monitor calcium associated with cancer dialysis. In fact, cancer-associated hypercalcemia (CAH) is the most common metabolic disorder in cancer patients. CAH remains associated with adverse outcomes. Hypercalcemia is a condition in which there is too much calcium in the blood. It is the most common life-threatening cancer complication in adults.

[0214] Hypercalcemia occurs in 10% to 20% of adults with cancer and develops as a complication in 10% to 20% of cancer patients. Cancer-associated hypercalcemia usually occurs late in the development of solid tumors and is a predictor of poor prognosis. Management of hypercalcemia is based on the presence of characteristic symptoms and the severity of calcium elevation. Patients with malignant hypercalcemia typically have symptoms and significantly elevated calcium levels.

[0215] Dialysis can have a rapid effect on calcium loss and remains a viable option for reducing hypercalcemia. Hemodialysis can be considered for patients with acute hypercalcemia using very low calcium dialysate (≤1 mmol / L), and monitoring serum calcium concentration using the concentration sensor described in the embodiments of this specification can provide significant advantages for treatment feedback.

[0216] While the invention has been described in conjunction with embodiments that are presently considered to be the most practical and preferred, it should be understood that the invention is not limited to the disclosed embodiments, but rather is intended to cover modifications and arrangements included within the scope of the appended claims.

Claims

1. An extracorporeal blood processing device (1), comprising: The filter unit (2) has a primary chamber (3) and a secondary chamber (4) separated by a semi-permeable membrane (5); The extracorporeal blood circuit (6) includes a blood extraction line (6a) connected to an inlet (3a) of the primary chamber (3) and a blood return line (6b) connected to an outlet (3b) of the primary chamber (3), and the extracorporeal blood circuit (6) is configured to be connected to the patient (P). Blood pump (7) acts on extracorporeal blood circuit (6) to pump blood through said extracorporeal blood circuit (6). The fluid circuit (8) includes at least one supply line (9, 16, 17, 18) and a waste line (10), wherein at least one supply line (9, 16, 17, 18) is connected to the inlet (4a) of the secondary chamber (4) and / or the extracorporeal blood circuit (6); and the waste line (10) is connected to the outlet (4b) of the secondary chamber (4). The sampling circuit (27) includes a bypass line (28) that connects at least one supply line (9, 16, 17, 18) to the waste line (10). A fluid pump assembly (29) acts on a sampling circuit (27) and controls the fluid pump assembly (29) in a first activation state and a second activation state, respectively. In the first activation state, the fluid pump assembly (29) causes at least one fluid passing through the fluid circuit (8) to flow from at least one supply line (9, 16, 17, 18) to the waste line (10) through a bypass line (28). In the second activation state, the fluid pump assembly (29) causes at least one fluid passing through the fluid circuit (8) to flow from the waste line (10) to at least one supply line (9, 16, 17, 18) through the bypass line (28). A concentrate sensor (30), placed on a bypass line (28), is used to monitor the concentration of at least one substance that can be detected entering at least one fluid passing through the fluid loop (8); The control unit (100) is operatively connected to the concentration sensor (30) and the fluid pump assembly (29). The control unit (100) is configured to control the fluid pump assembly (29) in a first active state or a second active state, and to receive signals from the concentrate sensor (30) and to determine the concentration (Csup, Ceff) of at least one substance.

2. The extracorporeal blood processing device according to claim 1, wherein, The fluid circuit (8) includes: a source (11, 19, 21, 23) of supply fluid connected to one end of at least one supply line (9, 16, 17, 18), a supply pump (13, 20, 22, 24) acting on at least one supply line (9, 16, 17, 18), and a waste pump (14) acting on a waste line (10), wherein at least one fluid is either supply fluid or waste fluid flowing out of the secondary chamber (4); and a control unit (100) is operatively connected to the supply pump (13, 20, 22, 24) and the waste pump (14). The control unit (100) is configured to control the supply pump (13, 20, 22, 24) and / or the waste pump (14), and optionally, is configured to control valves (32, 33, 35, 37) to allow the supply fluid to flow into the extracorporeal blood circuit (6) and / or the secondary chamber (4), and to allow the waste fluid to flow out of the secondary chamber (4). The control unit (100) is configured as follows: In the first activated state, the fluid pump assembly (29) is driven, and a signal from the concentrate sensor (30) is acquired to determine the concentration (Csup) of at least one substance entering the supply fluid; or In the second activated state, the fluid pump assembly (29) is driven and a signal from the concentrate sensor (30) is acquired to determine the concentration (Ceff) of at least one substance entering the waste fluid.

3. The extracorporeal blood processing device according to claim 2, wherein, The control unit (100) is configured to estimate the solute removal rate (J) of at least one substance through the following procedure: The flow rate (Qeff) of the received waste liquid fluid; The solute removal rate (J) is calculated based on the concentration (Ceff) of at least one substance entering the waste liquid fluid and the flow rate (Qeff) of the waste liquid fluid. Optionally, the program includes: Receive at least one supply fluid flow rate (Qsup); The solute removal rate (J) is also calculated based on the concentration (Csup) of at least one substance entering at least one supply fluid and the flow rate (Qsup) of at least one supply fluid.

4. The extracorporeal blood processing device according to claim 3, wherein, The control unit (100) is configured to estimate the clearance or dialysis rate (K / D) of at least one substance by: estimating the blood concentration (Cb_est) of the same substance at the inlet (3a) of the primary chamber (3); and calculating the clearance or dialysis rate (K / D) of at least one substance based on the solute removal rate (J) and the estimated blood concentration (Cb_est) of the same substance at the inlet (3a) of the primary chamber (3).

5. The extracorporeal blood processing device according to claim 4, wherein, Estimating the blood concentration (Cb_est) of the same substance at the inlet (3a) of the primary chamber (3) includes: ensuring a balance between the concentration (Ceff_eq) of at least one substance entering the waste fluid and the blood concentration (Cb) of the same substance at the inlet (3a) of the primary chamber (3), such that the concentration (Ceff) of at least one substance entering the waste fluid is equal to or proportional to the blood concentration (Cb) of at least one substance at the inlet (3a) of the primary chamber (3); wherein the balance is ensured by changing the flow rate (Qsup) of at least one supply fluid and / or the flow rate (Qeff) of the waste fluid and / or the blood flow rate (Qb) set for extracorporeal blood treatment.

6. The extracorporeal blood processing device according to claim 5, wherein, Balance is ensured by waiting a settling time (t) after changing the flow rate of at least one supply fluid (Qsup) and / or waste fluid (Qeff) and / or blood flow (Qb).

7. The extracorporeal blood processing device according to any one of claims 5 or 6, wherein, After estimating the blood concentration (Cb_est), the control unit is configured, or the method is used, to: return the flow rate Qsup of at least one supply fluid and / or the flow rate Qeff of the waste fluid and / or the blood flow rate Qb to the prescribed value.

8. The extracorporeal blood processing device according to claim 4, wherein, Estimating the blood concentration (Cb_est) of the same substance at the inlet (3a) of the primary chamber (3) includes: recirculating at least a portion of the waste fluid from the outlet (4b) of the secondary chamber (4) through the sampling loop (27) and back to the inlet (4a) of the secondary chamber (4); measuring the concentration of the substance in the recirculated waste fluid, optionally periodically; waiting until the concentration of the substance becomes stable, or extrapolating the steady-state concentration of the substance; the estimated blood concentration (Cb_est) of the substance at the inlet (3a) of the primary chamber (3) is a stable concentration or an extrapolated steady state; optionally, setting the valve in an appropriate state to guide the waste fluid.

9. The extracorporeal blood processing device according to any one of claims 1 to 8, wherein, At least one supply line (9, 16, 17, 18) includes: Dialysis tubing (9) connected to the inlet of the secondary chamber (4), dialysis pump (13) acting on dialysis tubing (9), and a source (11) of dialysis fluid connected to one end of dialysis tubing (9). and / or At least one supply line (9, 16, 17, 18) includes: At least one alternative infusion line (16, 17, 18) is connected upstream or downstream of the filter unit (2) to an extracorporeal blood circuit or directly to the patient (P). At least one alternative infusion pump (20, 22, 24) acting on at least one alternative infusion line (16, 17, 18). At least one source (19, 21, 23) of replacement solution connected to one end of at least one alternative infusion line (16, 17, 18). The bypass line (28) connects at least one alternative infusion line (16, 17, 18) to the waste line (10); or The bypass line (28) connects the dialysis line (9) to the waste liquid line (10), and the bypass line (28) also includes a supply line (31, 34, 36) that connects at least one alternative infusion line (16, 17, 18) to the bypass line (28) at a location between the dialysis line (9) and the concentrate sensor (30).

10. The extracorporeal blood processing device according to claim 2 or 3, wherein, The fluid circuit (8) also includes an auxiliary source (41) for auxiliary fluid, which is connected to a bypass line (28) at a location between at least one supply line (9, 16, 17, 18) and the concentrate sensor (30); wherein the control unit (100) is configured to: Drive fluid pump assembly (29), and optionally, configure as a control valve to allow auxiliary fluid to flow through bypass line (28).

11. The extracorporeal blood processing device according to claim 10, wherein, The auxiliary fluid is a calibration fluid, and the control unit (100) is configured to calibrate the concentrate sensor (100) as the auxiliary fluid flows through the bypass line (28).

12. The extracorporeal blood processing device according to any one of claims 1 to 11, wherein, The control unit (100) is configured to control the extracorporeal blood processing device to perform extracorporeal blood processing on a patient (P), and is configured to determine the concentration of at least one substance or monitor at least one substance during extracorporeal blood processing.

13. The extracorporeal blood processing device according to any one of claims 1 to 12, wherein, The fluid pump assembly (29) includes a single reversible pump that acts on the bypass line (28).

14. The extracorporeal blood processing device according to any one of claims 1 to 12, wherein, The fluid pump assembly (29) includes: a single pump (54) configured to pump in the same direction at all times; a first bypass branch (55) and a second bypass branch (56) connecting the bypass line (28) at points upstream and downstream of the single pump (54); and assembly valves (57, 58, 59, 60) placed on the first bypass branch (55), the second bypass branch (56) and the bypass line (28), wherein a control unit (100) is configured to control the assembly valves (57, 58, 59, 60) to arrange the fluid pump assembly (29) in a first active state or a second active state.

15. The extracorporeal blood processing device according to any one of claims 1 to 14, wherein, The sampling circuit (27) is disposable, or part of a disposable kit, or can be connected to a disposable kit, which includes an extracorporeal blood circuit (6) and a fluid circuit (8).

16. The extracorporeal blood processing device according to any one of claims 1 to 15, wherein, At least one substance may be urea, creatinine, uric acid, glucose, electrolytes, or lactate.

17. The extracorporeal blood processing device according to any one of claims 1 to 16 in combination with claim 2, wherein, The bypass line (28) is connected to the waste line (10) downstream of the waste pump (14).

18. The extracorporeal blood processing device according to any one of claims 1 to 17 in combination with claim 2, wherein the circulation loop is defined by a bypass line (28), a portion of a waste line (10), a portion of a dialysis line (9) and a secondary chamber (4). in, The circulation loop includes a fluid pump assembly (29) and a waste liquid pump (14).

19. The extracorporeal blood processing device according to any one of claims 1 to 18 in combination with claim 9, wherein in a first activated state and / or a second activated state, the control unit (100) is configured to simultaneously activate the dialysis pump (13), the fluid pump assembly (29), and the waste pump (14) or maintain the activation of the dialysis pump (13), the fluid pump assembly (29), and the waste pump (14).

20. The extracorporeal blood processing device according to any one of claims 1 to 19 in combination with claim 9, wherein once the first activation state is triggered, the control unit (100) is configured to adjust the flow rate of the dialysis pump (13). And among them, Once the second activation state is triggered, the control unit (100) is configured to adjust the flow rate of the dialysis pump (13).

21. The extracorporeal blood processing device according to any one of claims 1 to 20, wherein when the first activation state and the second activation state are triggered, the control unit (100) is configured to adjust the flow rate of the dialysis pump (13) so as to maintain at least one constant between the flow rate at the inlet of the secondary chamber (4) and the ultrafiltration rate in the filtration unit (2) relative to the processing state prior to the first activation state and / or the second activation state, said ultrafiltration rate being defined as the flow rate difference between the flow rate at the inlet of the secondary chamber (4) and the flow rate at the outlet of the secondary chamber (4).

22. The extracorporeal blood processing device according to claim 21, wherein: - Once the first activation state is triggered, the control unit (100) is configured to increase the flow rate of the dialysis pump (13); and / or - Once the second activation state is triggered, the control unit (100) is configured to reduce the flow rate of the dialysis pump (13).

23. The extracorporeal blood processing device according to any one of claims 1 to 22, wherein, In the second activation state, the control unit (100) is configured to activate the fluid pump assembly (29) to generate a flow rate in a second direction from the waste line (10) to at least one supply line (9, 16, 17, 18), wherein the control unit is also configured to keep the fluid pump assembly (29) activated only in the second direction during the second activation state, and in particular, wherein the control unit is configured not to change the flow direction of the fluid pump assembly (29) during the second activation state.

24. The extracorporeal blood processing device according to any one of claims 1 to 23, wherein, The control unit is configured to calculate computational parameters, including at least one of the following: solute removal rate (J) of at least one substance, clearance rate or dialysis rate (K / D) of at least one substance in the filtration unit (2), and concentration of the substance in the blood. The control unit is configured to calculate the calculation parameters based on the concentration of at least one substance entering the supply fluid (Csup) and the concentration of at least one substance entering the waste fluid (Ceff).

25. The extracorporeal blood processing device according to claim 24, wherein, The at least one substance is present in the supply fluid. Furthermore, optionally, at least one of the substances is calcium.

26. An extracorporeal blood processing device (1), comprising: The filter unit (2) has a primary chamber (3) and a secondary chamber (4) separated by a semi-permeable membrane (5); The extracorporeal blood circuit (6) includes a blood extraction line (6a) connected to an inlet (3a) of the primary chamber (3) and a blood return line (6b) connected to an outlet (3b) of the primary chamber (3), and the extracorporeal blood circuit (6) is configured to be connected to the patient (P). Blood pump (7) acts on extracorporeal blood circuit (6) to pump blood through said extracorporeal blood circuit (6). The fluid circuit (8) includes at least one supply line (9, 16, 17, 18) and a waste line (10). The at least one supply line (9, 16, 17, 18) is connected to the inlet (4a) of the secondary chamber (4) and / or the extracorporeal blood circuit (6). The waste line (10) is connected to the outlet (4b) of the secondary chamber (4). The at least one supply line (9, 16, 17, 18) includes a dialysis line (9) connected to the inlet of the secondary chamber (4), a dialysis pump (13) acting on the dialysis line (9), and a source (11) of dialysis fluid connected to one end of the dialysis line (9). The fluid circuit (8) includes a waste pump (14) acting on the waste line (10). The sampling circuit (27) includes a bypass line (28) that connects at least one supply line (9, 16, 17, 18) to the waste line (10), wherein the bypass line (28) is connected to the waste line (10) downstream of the waste pump (14). The fluid pump assembly (29) acts on the sampling circuit (27) and controls the fluid pump assembly (29) in a first activation state and a second activation state, respectively. In the first activation state, the fluid pump assembly (29) causes at least one fluid passing through the fluid circuit (8) to flow from at least one supply line (9, 16, 17, 18) to the waste line (10) through the bypass line (28). In the second activation state, the fluid pump assembly (29) causes at least one fluid passing through the fluid circuit (8) to flow from the waste line (10) to at least one supply line (9, 16, 17, 18) through the bypass line (28). A concentrate sensor (30), placed on a bypass line (28), is used to monitor the concentration of at least one substance that can be detected entering at least one fluid passing through the fluid loop (8); A control unit (100) is operatively connected to a concentration sensor (30) and a fluid pump assembly (29). The control unit (100) is configured to control the fluid pump assembly (29) in a first active state or a second active state, and to receive signals from the concentrate sensor (30) and to determine the concentration (Csup, Ceff) of at least one substance. In the first activation state and / or the second activation state, the control unit (100) is configured to simultaneously activate the dialysis pump (13), the fluid pump assembly (29) and the waste liquid pump (14) or maintain the activation of the dialysis pump (13), the fluid pump assembly (29) and the waste liquid pump (14).

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